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BetterLife To Present BETR-001 Preclinical Data at the 61ST Annual Meeting of the American College of Neuropsychopharmacology in Phoenix, Arizona
Investing News Network
BetterLife Pharma Inc. ("BetterLife" or the "Company") (CSE: BETR OTCQB: BETRF FRA: NPAU ), an emerging biotech company focused on the development and commercialization of cutting-edge treatments for mental disorders, today announced that one of its scientific collaborators, Dr. Argel Aguilar-Valles from Carleton University's Department of Neuroscience (Ottawa, Canada), will present on the anti-depressant activity of 2-bromo-LSD ("BETR-001"), the Company's lead compound, at the upcoming ACNP Conference being held December 4 to 7 at Phoenix, Arizona, USA. BETR-001 is a non-hallucinogenic Lysergic Acid Diethylamide ("LSD") derivative molecule. Dr. Aguilar-Valles will present preclinical data supporting the acute and long-term anti-depressant activity of BETR-001 monotherapy in animal models. Furthermore, the data shows that BETR-001 promotes structural neuroplasticity in brain neurons and this effect is partly mediated by the activation of 5-HT2A receptor. Dr. Ahmad Doroudian, CEO of BetterLife commented, "BETR-001 is a uniquely positioned LSD derivative with the potential to be as effective as LSD in various neuropsychiatric and neurological disorders without the burden of being hallucinogenic. Because of its non-hallucinogenic nature, BETR-001 will not have all the LSD requirements of administration in specialized clinics under special treatment protocols, the LSD controlled substance regulatory issues which impact manufacturing, distribution and patient access, and the overall associated high treatment costs for all these parameters. Additionally, BETR-001 is protected by BetterLife's composition, method-of-use, synthesis and formulation patents (issued and provisional)." He further added, "BETR-001 IND-enabling studies are being completed and we hope to file its IND and begin human trials by mid-2023."
About BetterLife Pharma
BetterLife Pharma Inc. is an emerging biotechnology company primarily focused on developing and commercializing two compounds, BETR-001 and BETR-002, to treat neuro-psychiatric and neurological disorders.
BETR-001, which is in preclinical and IND-enabling studies, is a non-hallucinogenic and non-controlled LSD derivative in development and it is unique in that it is unregulated and, therefore, could be self-administered. BetterLife's synthesis patent for BETR-001 eliminates regulatory hurdles and its pending patent for composition and method of use covers treatment of depression, anxiety, post-traumatic stress disorder, neuropathic pain and other neuro-psychiatric and neurological disorders.
BETR-002, which is in preclinical and IND-enabling studies, is based on honokiol, the active anxiolytic ingredient of magnolia bark. BetterLife's pending method of use and formulations patent covers treatment of anxiety related disorders, including benzodiazepine dependency.
BetterLife also owns a drug candidate for the treatment of viral infections such as COVID-19 and other respiratory viral infections.
For further information, please visit BetterLife Pharma .
About the Department of Neuroscience at Carleton University
Carleton Neuroscience has an international reputation for research on stress and its effects on brain functioning and mental health. The department has an interdisciplinary approach to understanding the emergence, prevention and treatment of mental and physical disorders.
For more information, please visit www.carleton.ca/neuroscience .
David Melles, Investor Relations Manager
Email: David.Melles@blifepharma.com
No securities exchange has reviewed nor accepts responsibility for the adequacy or accuracy of the content of this news release. This news release contains forward-looking statements relating to product development, licensing, commercialization and regulatory compliance issues and other statements that are not historical facts. Forward-looking statements are often identified by terms such as "will", "may", "should", "anticipate", "expects" and similar expressions. All statements other than statements of historical fact, included in this release are forward-looking statements that involve risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the Company's expectations include the failure to satisfy the conditions of the relevant securities exchange(s) and other risks detailed from time to time in the filings made by the Company with securities regulations. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date of this news release and the Company will update or revise publicly any of the included forward-looking statements as expressly required by applicable law.
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BetterLife PharmaCSE:BETRPharmaceutical Investing
BETR:CNX
BetterLife Announces Engagement of Bloom Burton Securities Inc. and Provides Summary of 2022 Accomplishments
BetterLife Pharma Inc. ("BetterLife" or the "Company") (CSE: BETR OTCQB: BETRF FRA: NPAU ), an emerging biotech company focused on the development and commercialization of cutting-edge treatments for mental disorders, is pleased to announce the engagement of Bloom Burton Securities Inc. ("Bloom Burton") for strategic advisory services to support BetterLife's growth and development initiatives towards clinical trials.
"We are very excited to be working with Bloom Burton, Canada's leading healthcare investment banking firm," said Ahmad Doroudian, CEO of BetterLife. "Bloom Burton has extensive understanding of the overall biotechnology and healthcare landscape and the emerging psychedelics space specifically, which will help advance our clinical trial initiatives and accomplish our financing needs."
BetterLife is also pleased to highlight the 2022 accomplishments for the advancement of its non-hallucinogenic therapeutics to treat a wide range of mental health conditions and neurological disorders as well as accomplishments of its wholly owned subsidiary MedMelior's proprietary interferon alpha2b formulations to treat HPV and respiratory viral infections.
Development of scaled-up (kg batch size) manufacturing of BetterLife's proprietary form of 2-bromo-LSD ("BETR-001") using BetterLife's proprietary synthetic pathway. The starting material and whole synthetic pathway do not involve any controlled substance and, therefore, are not bound by controlled substance regulations. Both the synthetic route and the end-product are proprietary (BetterLife's provisional patents).
Initiation of GMP manufacturing of BETR-001.
A comprehensive preclinical in-vitro and in-vivo characterization of BETR-001 conducted in collaboration with three leading investigators in this field: Dr. Adam L. Halberstadt (University of California San Diego, USA), Dr. Argel Aguilar-Valles (Carleton University, Canada), and Dr. John D. McCorvy (Medical College of Wisconsin, USA).
The studies include an in vitro pharmacological profiling of BETR-001 over 30 key neuroreceptors in parallel with its parent compound LSD, as well as in-vivo studies in mouse models, showing the non-hallucinogenic profile of BETR-001 as well as its effective structural neuroplasticity and anti-depressant profile. Furthermore, the research provides insight into the mechanism for the non-hallucinogenic activity of BETR-001, as well as other key pharmacological differences between BETR-001 and LSD which could potentially translate into significant therapeutic benefits of BETR-001.
At the end of 2022, the manuscript on the BETR-001 preclinical data was submitted to a high impact peer-reviewed scientific journal for publication and is currently awaiting review outcome.
Initiation of IND-enabling GLP toxicology studies. Studies are ongoing.
IND-enabling studies are based on guidance from the BETR-001 pre-IND FDA meeting held in 2021.
Filing of a PCT patent application along with a U.S. application for LSD derivatives, including 2-bromo-LSD. The applications cover compositions of these derivatives; their synthesis without involving controlled substances; and their use in the treatment of a range of neuropsychiatric and neurological conditions, including depression, anxiety, PTSD, and neuropathic pain.
Scientific presentations on BETR-001 preclinical data were made at the following conferences:
Canadian Association for Neuroscience (CAN) / May 12-15, 2022 / Toronto, Canada.
Federation of European Neuroscience Societies (FENS) / July 9-13, 2022 / Paris, France.
61 st Annual Meeting of the American College of Neuropsychopharmacology (ACNP) / December 4-7, 2022 / Phoenix, Arizona.
Abstract submitted and accepted for presentation at the Annual Conference of Society of Biological Psychiatry (SOBP) / April 27-29, 2023 / San Diego, California.
MedMelior
MedMelior's interferon alpha 2b ("IFNa2b") provisional patent (manufacturing, cell bank, formulation, and use) was entered into national filing phase in different countries.
A Phase 1 trial in healthy subjects was completed with MM-003 (IFNa2b in MedMelior's proprietary inhalation formulation). Trial was an independent investigator study conducted in Chile by the Pontificia Universidad Católica de Chile. Data showed inhaled MM-003 was safe and well tolerated.
A Phase 2 trial of treatment with MM-003, with twice daily inhalation, in early stage COVID-19 patients was conducted in Chile. The trial was an independent investigator study conducted in Chile by the Pontificia Universidad Católica de Chile. Patient treatments were completed and data analysis is ongoing.
MedMelior continues to pursue strategic options for funding and partnership to develop its MM-001 and MM-003 programs.
BETR-001, which is in preclinical and IND-enabling studies, is a non-hallucinogenic and non-controlled LSD derivative in development and it is unique in that it is unregulated and therefore can be self-administered. BetterLife's synthesis patent for BETR-001 eliminates regulatory hurdles and its pending patent for composition and method of use covers treatment of depression, cluster headaches, post-traumatic stress disorder and other neuro-psychiatric and neurological disorders.
BETR-002, which is in preclinical and IND-enabling studies, is based on honokiol, the active anxiolytic ingredient of magnolia bark. BetterLife's pending method of use and formulations patent covers treatment of anxiety related disorders including benzodiazepine dependency.
BetterLife also owns a drug candidate for the treatment of viral infections such as COVID-19 and is in the process of seeking strategic alternatives for further development.
BetterLife Announces Closing of Private Placement
BetterLife Pharma Inc. ("BetterLife" or the "Company") (CSE: BETR OTCQB : BETRF FRA: NPAU ) is pleased to announce that it has closed a non-brokered private placement (the "Offering") by issuing 3,160,000 common shares at a price of USD$0.15 per common share for gross proceeds of USD$474,000. The common shares issued pursuant to the Offering are subject to a hold period under applicable securities laws, which hold period expires four months and a day following the date of issuance. BetterLife will use the proceeds for working capital purposes and for advancement of pre-clinical and clinical programs. Negev Capital and certain European-based investors participated in the Offering.
"We are delighted to support BetterLife in the development of promising second generation psychedelics that have significant clinical advantages for neuropsychiatric conditions. Indeed, in the race to an at-home (i.e. non trip-inducing) medication, they are in the lead. With excellent IP, a solid team, and a well-crafted strategy, BetterLife is poised to succeed," said Ken Belotsky, Partner at Negev Capital.
Concurrently, BetterLife announces that its convertible debtholder has converted the full outstanding amount of the debt to common shares of the Company. The principal amount (C$250,000) and accrued interest (C$58,027) have been converted at an agreed conversion price of C$0.20 per share. As a result, the Company has issued 1,540,135 common shares upon conversion.
"We are extremely pleased to have such strategic investment from Negev Capital. Investments from groups, such as Negev, provide strategic support and significant confirmation of our plans for the development of BETR-001 for the treatment of mental health disorders," said Ahmad Doroudian, CEO of BetterLife.
About Negev Capital
Negev Capital ("Negev") is a psychedelic medical intervention investment fund with assets of USD$25+ million. Negev invests in drug discovery, with a focus on preclinical and/or Phase 1 stages of development. Negev aims to support those early-stage companies in need of capital that promote the thoughtful, responsible, medical use of psychedelic medication for psychiatric disorders, and who have excellent management and science teams, and solid intellectual property.
Negev believes that psychedelic medications will be not only disruptive to the practice of psychiatry but hold the potential to reduce enormous amounts of human suffering, and is committed to helping the field mature, and further promote ways for these treatments to reach all of those in need.
For further information, please visit Negev Capital .
BetterLife Pharma Contact Information
BetterLife Files Comprehensive Patent for BETR-001 and Other LSD Derivatives
BetterLife Pharma Inc. ("BetterLife" or the "Company") (CSE: BETR OTCQB: BETRF FRA: NPAU ), an emerging biotech company focused on the development and commercialization of cutting-edge treatments for mental disorders, is pleased to announce filing of a PCT patent application along with a U.S. application for lysergic acid diethylamide ("LSD") derivatives, including 2-bromo-LSD. The applications cover compositions of these derivatives for their use in the treatment of a range of neuropsychiatric and neurological conditions, including depression, anxiety, cluster headaches and pain.
BetterLife is currently developing a new composition of 2-bromo-LSD ("BETR-001") covered by these patent filings. BETR-001 is a second-generation LSD derivative molecule that does not cause hallucinations, and therefore is not subject to global controlled substance regulations. In addition, the synthesis of BETR-001 is via non-controlled substance synthetic routes, and therefore not subject to controlled substance regulatory restrictions.
BetterLife is already in advanced stages of GMP manufacturing of BETR-001 and completing the necessary preclinical IND-enabling studies for BETR-001. BetterLife expects to file the BETR-001 IND and start Phase 1, in healthy subjects, in H1 of 2023.
Ahmad Doroudian, CEO of BetterLife, commented, "The inventions covered by the patent filings are comprehensive and involve significant body of data including composition of matter, preclinical in-vitro and in-vivo characterization of BETR-001 that will be submitted for publication in a prestigious peer-reviewed journal, in the near future. Based on the data generated to date, we believe BETR-001 holds great promise in becoming a major treatment for a range of mental health and neurological conditions, including depression, anxiety, pain and related disorders."
BetterLife Pharma Inc. Contact Information
BetterLife and Collaborators to Submit Key Joint Research Publication
BetterLife Pharma Inc. ("BetterLife" or the "Company") (CSE: BETR OTCQB: BETRF FRA: NPAU ), an emerging biotech company focused on the development and commercialization of cutting-edge treatments for mental disorders, is pleased to announce that BetterLife is working with its collaborators on a key research publication on BETR-001, its proprietary 2-bromo-LSD, and plans to submit it for review to a prestigious peer-reviewed journal by end of September 2022.
This publication will present data from a comprehensive preclinical in-vitro and in-vivo characterization of BETR-001 conducted in collaboration with three leading investigators in this field: Dr. Adam L. Halberstadt (University of California San Diego, USA), Dr. Argel Aguilar-Valles (Carleton University, Canada), and Dr. John D. McCorvy (Medical College of Wisconsin, USA). The publication will include a pharmacological profiling of BETR-001 against over 30 key neuroreceptors in parallel with its parent compound LSD, as well as in-vivo studies in mouse models, showing the non-hallucinogenic profile of BETR-001 as well its effective structural neuroplasticity and anti-depressant profile. Furthermore, the research will provide insight into the mechanism for the non-hallucinogenic activity of BETR-001, as well as other key pharmacological differences between BETR-001 and LSD which could potentially translate into significant therapeutic benefits of BETR-001. Subject to the journal's regulations, a pre-publication preprint will be posted as soon as possible for the public.
Ahmad Doroudian, CEO of BetterLife said, "This is the first comprehensive preclinical characterization of 2-bromo-LSD, the non-hallucinogenic congener of LSD." He added, "The studies were conducted using BetterLife's proprietary 2-bromo-LSD (patent pending). The mechanistic data showing the differences between LSD and BETR-001 highlight the significant potential therapeutic benefits of BETR-001. We are excited to be able to study these in our BETR-001 human clinical trials projected to start in 2023."
BetterLife Lead Drug Promotes Structural Neural Plasticity with Possible Nootropic Effects Similar to That of LSD Without Hallucinogenic Side Effects
BetterLife Pharma Inc. ("BetterLife" or the "Company") (CSE: BETR OTCQB: BETRF FRA: NPAU ), is an emerging biotech company focused on the development and commercialization of cutting-edge treatments for mental disorders.
A recent study, published in Experimental Neurology , has provided some new evidence that LSD has nootropic effects which are believed to be driven by neuroplasticity promotion. Researchers found that LSD increased neuroplasticity in 'human brain organoids, increased novelty preference in rats, and improved memory performance in humans.' Increased structural plasticity in the brain neurons (mainly prefrontal cortex) has also been linked to the sustained antidepressant effects.
BetterLife's neuroplasticity study similarly demonstrated that, in the treatment of rat embryonic cortical neurons the Company's lead drug, BETR-001 (2-bromo-LSD) increases the structural complexity of neurons (dendrite growth and complexity) indicating the neural plasticity activity of BETR-001. In certain measurements of structural plasticity in neurons, BETR-001 performs better than ketamine in this model.
"These results confirm that our proprietary BETR-001, an LSD analog, retains the anti-depressant and neural plasticity activity of LSD without causing hallucination . The fact that BETR-001 can promote structural plasticity in the prefrontal cortex neurons indicates its therapeutic effects in depression and related disorders, providing a potential patient friendly treatment addressing a very large unmet medical need affecting large number of patients globally," said Ahmad Doroudian, CEO of BetterLife.
BETR-001, which is in preclinical and IND-enabling studies, is a non-hallucinogenic and non-controlled LSD derivative in development and it is unique in that it is unregulated and, therefore, can be self-administered. BetterLife's synthesis patent for BETR-001 eliminates regulatory hurdles and its pending patent for composition and method of use covers treatment of depression, cluster headaches, post-traumatic stress disorder and other neuro-psychiatric and neurological disorders.
FDA Approves KEYTRUDA® as Adjuvant Treatment Following Surgical Resection and Platinum-Based Chemotherapy for Patients With Stage IB , II, or IIIA Non-Small Cell Lung Cancer
Approval based on KEYNOTE-091 trial, which demonstrated a clinically meaningful improvement in disease-free survival with KEYTRUDA in these patients following surgical resection and platinum-based chemotherapy versus placebo
Approval marks fifth indication for KEYTRUDA-based regimens in NSCLC and 34th indication for KEYTRUDA in the US
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck's anti-PD-1 therapy, as a single agent, for adjuvant treatment following surgical resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 centimeters [cm]), II, or IIIA non-small cell lung cancer (NSCLC).
The approval is based on data from the pivotal Phase 3 KEYNOTE-091 trial, also known as EORTC-1416-LCGETOP-8-15 PEARLS. The major efficacy outcome measure was investigator-assessed disease-free survival (DFS). In patients who received adjuvant platinum-based chemotherapy following surgical resection, KEYTRUDA reduced the risk of disease recurrence or death by 27% (hazard ratio [HR]=0.73 [95% CI, 0.60-0.89]) versus placebo regardless of PD-L1 expression. The median DFS in patients regardless of PD-L1 expression who received adjuvant platinum-based chemotherapy following surgical resection was nearly five years (58.7 months) for the KEYTRUDA arm versus nearly three years (34.9 months) for the placebo arm, translating to a nearly two-year (23.8 months) DFS improvement versus placebo. In an exploratory subgroup analysis of the 167 patients (14%) who did not receive adjuvant chemotherapy, the DFS HR was 1.25 (95% CI, 0.76-2.05).
"While there have been many advances for patients with metastatic disease, surgery remains the typical treatment for people with stage IB, II and IIIA non-small cell lung cancer. Unfortunately, many of these patients who undergo surgery still see their disease return," said Roy S. Herbst, M.D., Ph.D., deputy director and chief of medical oncology, Yale Cancer Center and Smilow Cancer Hospital and ensign professor of medicine (medical oncology) and professor of pharmacology, Yale School of Medicine. "Today's approval for KEYTRUDA offers a new, important immunotherapy treatment option for stage IB (T2a ≥4 cm), II, or IIIA patients with non-small cell lung cancer following surgery and adjuvant chemotherapy. This provides, for the first time, an adjuvant immunotherapy treatment option for non-small cell lung cancer patients with stage IB disease and regardless of PD-L1 expression."
The adverse reactions observed in KEYNOTE-091 were generally similar to those occurring in other patients with NSCLC receiving KEYTRUDA as a single agent, with the exception of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune- mediated adverse reactions are essential to ensure safe use of KEYTRUDA. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or permanently discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. For more information, see "Selected Important Safety Information" below.
"Six years ago, KEYTRUDA was the first anti-PD-1 therapy approved for the first-line treatment of metastatic non-small cell lung cancer and has changed the way metastatic disease is treated. Today's approval marks the fifth indication for KEYTRUDA in non-small cell lung cancer and the first indication for KEYTRUDA in patients with resected stage IB (T2a ≥4 cm), II, or IIIA disease following adjuvant chemotherapy," said Dr. Gregory Lubiniecki, vice president, oncology global clinical development, Merck Research Laboratories. "This is an important milestone as we continue our efforts to pursue meaningful advances for patients with non-small cell lung cancer."
With this approval, KEYTRUDA is the only immunotherapy with an approved option for NSCLC regardless of PD-L1 expression in both the adjuvant and metastatic settings. In addition to today's approval in the adjuvant setting, KEYTRUDA is indicated in combination with pemetrexed and platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations; in combination with carboplatin and either paclitaxel or paclitaxel protein-bound for the first-line treatment of patients with metastatic squamous NSCLC; as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic; and as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
Study design and additional data supporting the approval
KEYNOTE-091/EORTC-1416-LCG/ETOP-8-15 – PEARLS (ClinicalTrials.gov, NCT02504372 ) is a multicenter, randomized, triple-blind, placebo-controlled Phase 3 trial conducted in 1,177 patients with completely resected stage IB (T2a ≥4 cm), II, or IIIA NSCLC per the American Joint Committee on Cancer (AJCC) seventh edition. Patients had not received neoadjuvant radiotherapy or chemotherapy. Adjuvant chemotherapy up to four cycles was optional. Patients were ineligible if they had active autoimmune disease, were on chronic immunosuppressive agents or had a history of interstitial lung disease or pneumonitis.
Patients were randomized (1:1) to receive KEYTRUDA 200 mg or placebo intravenously every three weeks. Treatment continued until RECIST v1.1-defined disease recurrence as determined by the investigator, unacceptable toxicity or up to one year. Tumor assessments were conducted every 12 weeks for the first year, then every six months for years two to three, and then annually through year five. After year five, imaging was performed as per local standard of care. The major efficacy outcome measure was investigator-assessed DFS. An additional efficacy outcome was overall survival.
Of 1,177 patients randomized, 1,010 (86%) received adjuvant platinum-based chemotherapy following resection.
In the study, the median duration of exposure to KEYTRUDA was 11.7 months (range, 1 day to 18.9 months). Sixty-eight percent of patients in the KEYTRUDA arm were exposed to KEYTRUDA for ≥6 months.
The trial met its primary endpoint, demonstrating a statistically significant improvement in DFS in the overall population for patients randomized to the KEYTRUDA arm compared to patients randomized to the placebo arm. Overall survival results were not mature with only 42% of pre-specified OS events in the overall population.
KEYNOTE-091/EORTC-1416-LCG/ETOP-8-15 – PEARLS was conducted in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) and the European Thoracic Oncology Platform (ETOP).
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 81% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 25%, which is a 21% improvement over the last five years. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced. Only 5.8% of people in the U.S. who are eligible got screened for lung cancer in 2021.
About Merck's research in lung cancer
Merck is advancing research aimed at transforming the way lung cancer is treated, with a goal of improving outcomes for patients affected by this deadly disease. Through nearly 200 clinical trials evaluating more than 36,000 patients around the world, Merck is at the forefront of lung cancer research. In NSCLC, KEYTRUDA has five approved U.S. indications (see indications below) and is approved for advanced disease in more than 95 countries. Among Merck's research efforts are trials focused on evaluating KEYTRUDA in earlier stages of lung cancer as well as identifying new combinations and coformulations with KEYTRUDA.
About KEYTRUDA ® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry's largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA ® (pembrolizumab) Indications in the U.S.
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
See additional selected indications for KEYTRUDA in the U.S. after the Selected Important Safety Information
Selected Important Safety Information for KEYTRUDA
Severe and Fatal Immune-Mediated Adverse Reactions
KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.
Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.
Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.
Pneumonitis occurred in 41 (7%) patients, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. In adult patients who received adjuvant therapy for NSCLC, patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.
Immune-Mediated Colitis
KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (
Hepatotoxicity and Immune-Mediated Hepatitis
KEYTRUDA as a Single Agent
KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (
KEYTRUDA With Axitinib
KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.
Immune-Mediated Endocrinopathies
KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (
Hypophysitis
KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (
KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in
Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in
Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis
Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in
Immune-Mediated Nephritis With Renal Dysfunction
KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (
Immune-Mediated Dermatologic Adverse Reactions
KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti–PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.
Other Immune-Mediated Adverse Reactions
The following clinically significant immune-mediated adverse reactions occurred at an incidence of Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.
Infusion-Related Reactions
KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.
Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after anti–PD-1/PD-L1 treatments. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between anti–PD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using anti–PD-1/PD-L1 treatments prior to or after an allogeneic HSCT.
Increased Mortality in Patients With Multiple Myeloma
In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an anti–PD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.
Embryofetal Toxicity
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.
In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (≥20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).
In KEYNOTE-054, when KEYTRUDA was administered as a single agent to patients with stage III melanoma, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (≥1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (≥20%) with KEYTRUDA was diarrhea (28%). In KEYNOTE-716, when KEYTRUDA was administered as a single agent to patients with stage IIB or IIC melanoma, adverse reactions occurring in patients with stage IIB or IIC melanoma were similar to those occurring in 1011 patients with stage III melanoma from KEYNOTE-054.
In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).
In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.
In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (≥20%) was fatigue (25%).
In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).
Adverse reactions observed in KEYNOTE-091 were generally similar to those occurring in other patients with NSCLC receiving KEYTRUDA as a single agent, with the exception of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two fatal reactions of myocarditis occurred.
In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (≥20%) were fatigue (33%), constipation (20%), and rash (20%).
In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (≥20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).
In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (≥20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.
In KEYNOTE-204, KEYTRUDA was discontinued due to adverse reactions in 14% of 148 patients with cHL. Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA; those ≥1% were pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia, and sepsis. Three patients died from causes other than disease progression: 2 from complications after allogeneic HSCT and 1 from unknown cause. The most common adverse reactions (≥20%) were upper respiratory tract infection (41%), musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, rash, and cough (20% each).
In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those ≥1% were pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression: 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (≥20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (≥20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).
In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or mUC. Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).
In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or mUC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those ≥2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (≥20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).
In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those ≥2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).
Adverse reactions occurring in patients with MSI-H or dMMR CRC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.
In KEYNOTE-811, when KEYTRUDA was administered in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 6% of 217 patients with locally advanced unresectable or metastatic HER2+ gastric or GEJ adenocarcinoma. The most common adverse reaction resulting in permanent discontinuation was pneumonitis (1.4%). In the KEYTRUDA arm versus placebo, there was a difference of ≥5% incidence between patients treated with KEYTRUDA versus standard of care for diarrhea (53% vs 44%) and nausea (49% vs 44%).
The most common adverse reactions (reported in ≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, and insomnia.
In KEYNOTE-590, when KEYTRUDA was administered with cisplatin and fluorouracil to patients with metastatic or locally advanced esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates for surgical resection or definitive chemoradiation, KEYTRUDA was discontinued due to adverse reactions in 15% of 370 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were pneumonitis (1.6%), acute kidney injury (1.1%), and pneumonia (1.1%). The most common adverse reactions (≥20%) with KEYTRUDA in combination with chemotherapy were nausea (67%), fatigue (57%), decreased appetite (44%), constipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and weight loss (24%).
Adverse reactions occurring in patients with esophageal cancer who received KEYTRUDA as a monotherapy were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.
In KEYNOTE-826, when KEYTRUDA was administered in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab (n=307), to patients with persistent, recurrent, or first-line metastatic cervical cancer regardless of tumor PD-L1 expression who had not been treated with chemotherapy except when used concurrently as a radio-sensitizing agent, fatal adverse reactions occurred in 4.6% of patients, including 3 cases of hemorrhage, 2 cases each of sepsis and due to unknown causes, and 1 case each of acute myocardial infarction, autoimmune encephalitis, cardiac arrest, cerebrovascular accident, femur fracture with perioperative pulmonary embolus, intestinal perforation, and pelvic infection. Serious adverse reactions occurred in 50% of patients receiving KEYTRUDA in combination with chemotherapy with or without bevacizumab; those ≥3% were febrile neutropenia (6.8%), urinary tract infection (5.2%), anemia (4.6%), and acute kidney injury and sepsis (3.3% each).
KEYTRUDA was discontinued in 15% of patients due to adverse reactions. The most common adverse reaction resulting in permanent discontinuation (≥1%) was colitis (1%).
For patients treated with KEYTRUDA, chemotherapy, and bevacizumab (n=196), the most common adverse reactions (≥20%) were peripheral neuropathy (62%), alopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia (41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each), constipation and arthralgia (31% each), vomiting (30%), urinary tract infection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and decreased appetite (21%).
For patients treated with KEYTRUDA in combination with chemotherapy with or without bevacizumab, the most common adverse reactions (≥20%) were peripheral neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%), diarrhea (36%), constipation (28%), arthralgia (27%), vomiting (26%), hypertension and urinary tract infection (24% each), and rash (22%).
In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with previously treated recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).
Adverse reactions occurring in patients with HCC were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).
Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).
In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (≥1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (≥20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).
In KEYNOTE-564, when KEYTRUDA was administered as a single agent for the adjuvant treatment of renal cell carcinoma, serious adverse reactions occurred in 20% of patients receiving KEYTRUDA; the serious adverse reactions (≥1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis, and diabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2% including 1 case of pneumonia. Discontinuation of KEYTRUDA due to adverse reactions occurred in 21% of 488 patients; the most common (≥1%) were increased ALT (1.6%), colitis (1%), and adrenal insufficiency (1%). The most common adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).
Adverse reactions occurring in patients with MSI-H or dMMR endometrial carcinoma who received KEYTRUDA as a single agent were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a single agent.
Adverse reactions occurring in patients with TMB-H cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.
Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.
In KEYNOTE-522, when KEYTRUDA was administered with neoadjuvant chemotherapy (carboplatin and paclitaxel followed by doxorubicin or epirubicin and cyclophosphamide) followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent (n=778) to patients with newly diagnosed, previously untreated, high-risk early-stage TNBC, fatal adverse reactions occurred in 0.9% of patients, including 1 each of adrenal crisis, autoimmune encephalitis, hepatitis, pneumonia, pneumonitis, pulmonary embolism, and sepsis in association with multiple organ dysfunction syndrome and myocardial infarction. Serious adverse reactions occurred in 44% of patients receiving KEYTRUDA; those ≥2% were febrile neutropenia (15%), pyrexia (3.7%), anemia (2.6%), and neutropenia (2.2%). KEYTRUDA was discontinued in 20% of patients due to adverse reactions. The most common reactions (≥1%) resulting in permanent discontinuation were increased ALT (2.7%), increased AST (1.5%), and rash (1%). The most common adverse reactions (≥20%) in patients receiving KEYTRUDA were fatigue (70%), nausea (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and peripheral neuropathy (41% each), stomatitis (34%), vomiting (31%), headache (30%), arthralgia (29%), pyrexia (28%), cough (26%), abdominal pain (24%), decreased appetite (23%), insomnia (21%), and myalgia (20%).
In KEYNOTE-355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin) were administered to patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting (n=596), fatal adverse reactions occurred in 2.5% of patients, including cardio-respiratory arrest (0.7%) and septic shock (0.3%). Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA in combination with chemotherapy; the serious reactions in ≥2% were pneumonia (2.9%), anemia (2.2%), and thrombocytopenia (2%). KEYTRUDA was discontinued in 11% of patients due to adverse reactions. The most common reactions resulting in permanent discontinuation (≥1%) were increased ALT (2.2%), increased AST (1.5%), and pneumonitis (1.2%). The most common adverse reactions (≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were fatigue (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash (26% each), cough (23%), decreased appetite (21%), and headache (20%).
Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final last dose.
In KEYNOTE-051, 161 pediatric patients (62 pediatric patients aged 6 months to younger than 12 years and 99 pediatric patients aged 12 years to 17 years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 24 months).
Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults were pyrexia (33%), vomiting (30%), leukopenia (30%), upper respiratory tract infection (29%), neutropenia (26%), headache (25%), and Grade 3 anemia (17%).
Additional Indications for KEYTRUDA in the U.S.
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
who are not eligible for any platinum-containing chemotherapy, or
who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Non-muscle Invasive Bladder Cancer
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
in combination with platinum- and fluoropyrimidine-based chemotherapy, or
as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
About the Merck Access Program for KEYTRUDA
At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help appropriate patients who are prescribed KEYTRUDA have access to our anti-PD-1 therapy. The Merck Access Program provides reimbursement support for patients receiving KEYTRUDA, including information to help with out-of-pocket costs and co-pay assistance for eligible patients. More information is available by calling 855-257-3932 or visiting https://www.merckaccessprogram-keytruda.com/ .
About Merck's Patient Support Program for KEYTRUDA
Merck is committed to helping provide patients and their caregivers support throughout their treatment with KEYTRUDA. The KEY+YOU Patient Support Program provides a range of resources and support. For further information and to sign up, eligible patients may call 85-KEYTRUDA (855- 398-7832) or visit www.keytruda.com .
Merck's focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials .
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter , Facebook , Instagram , YouTube and LinkedIn .
Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA
This news release of Merck & Co., Inc., Rahway, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's Annual Report on Form 10-K for the year ended December 31, 2021 and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site ( www.sec.gov ).
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Julie Cunningham
Nikki Sullivan
Peter Dannenbaum
Damini Chokshi
News Provided by Business Wire via QuoteMedia
Merck Animal Health Receives U.S. FDA Approval of Expanded Indication for BRAVECTO Chews for Dogs
Portfolio expansion provides dogs broad-spectrum protection against Asian longhorned ticks
Merck Animal Health, known as MSD Animal Health outside of the United States and Canada, a division of Merck & Co., Inc., Rahway, N.J., USA (NYSE:MRK), today announced the U.S. Food and Drug Administration's approval of an expanded indication for BRAVECTO ® Chews for Dogs. The new indication treats and controls Asian longhorned ticks, which are an invasive Ixodid species located across more than one-third of the U.S 1,2 .
BRAVECTO Chews for Dogs is the first and only U.S. product labeled for the treatment and control of Asian longhorned tick infestations. These ticks have the potential to quickly become an important tick species within pet populations and have been known to carry various viral, bacterial and protozoal agents. This product label expansion is an important addition to the company's BRAVECTO product portfolio, which are extended duration flea and tick protection products that offer broad-spectrum, comprehensive parasite protection for dogs.
"The approval of this additional BRAVECTO use builds on the strong foundation and body of scientific evidence that we have established over the years with our broad-spectrum comprehensive line of parasite protection products," said Holger Lehmann, DVM, PhD, vice president, Pharmaceutical Research and Development, Merck Animal Health. "With BRAVECTO's new indication in Asian longhorned ticks, we have expanded our portfolio with an important claim in the fight against parasites, as well as provided dogs with flea and tick protection that delivers immediate and persistent killing activity."
BRAVECTO Chews for dogs is indicated for the treatment and prevention of flea infestations ( Ctenocephalides felis ), treatment and control of tick infestations ( Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), Rhipicephalus sanguineus (brown dog tick)] and Haemaphysalis longicornis (Asian longhorned tick) for 12 weeks and treatment and control of Amblyomma americanum (lone star tick) infestations for 8 weeks.
"Parasites pose serious animal and human health risks as fleas and ticks can transmit disease agents," said Kathryn Duncan, DVM, PhD, DACVM, parasitology field specialist, Merck Animal Health. "Protection against the Asian longhorned tick is critical because its prevalence is increasing throughout the country. This expanded indication from Merck Animal Health represents a scientific milestone in our continued commitment to providing the highest level of proven treatments in battling parasites faced by our pets."
BRAVECTO Chews for Dogs is part of the Merck Animal Health Companion Animal portfolio, which includes a broad range of veterinary medicines and vaccines, as well as the SURE PETCARE ™ brand platform of digitally connected products along with the HomeAgain ® brand-leading service provider in pet recovery.
BRAVECTO Chews for Dogs is available in five strengths (112.5, 250, 500, 1000, and 1400 mg fluralaner) per chew. To learn more about BRAVECTO and our innovative flea and tick treatments, visit us.bravecto.com .
About BRAVECTO ®
Since its introduction in 2014, BRAVECTO has provided longer-lasting flea and tick protection, with more than 250 million doses distributed in 85 countries over eight years. BRAVECTO is available in a variety of formulations, including products for both dogs and cats.
The flea lifecycle can last as long as 12 weeks, and monthly treatments may leave gaps in protection. Providing pets with continuous flea and tick protection is essential – whether the pet goes outside or not. Contrary to popular belief among pet owners, fleas and ticks are not only active in the spring and summer months and are a year-round risk. Fleas and ticks can easily latch onto dogs and cats, and can spread serious diseases. Fleas are the most common external parasite found on pets. BRAVECTO products are only available through licensed veterinarians.
BRAVECTO 1-MONTH Chews: indicated for dogs 8 weeks of age and older. The most commonly reported adverse reactions include itching, diarrhea, vomiting, decreased appetite, elevated ALT, lethargy, and weight loss. BRAVECTO 1-MONTH is not effective against A. americanum in puppies less than 6 months of age. BRAVECTO Chews for Dogs: The most commonly reported adverse reactions include vomiting, lethargy, diarrhea, anorexia and pruritus. In some cases, adverse events have been reported following use in breeding females. BRAVECTO Topical Solution for Dogs: The most commonly reported adverse reactions include vomiting, hair loss, diarrhea, lethargy, decreased appetite, and moist dermatitis/rash. BRAVECTO Topical Solution for Cats: The most commonly reported adverse reactions include vomiting, itching, diarrhea, hair loss, decreased appetite, lethargy, and scabs/ulcerated lesions. BRAVECTO Topical Solution for Cats is not effective against American dog ticks beyond 8 weeks of dosing. BRAVECTO PLUS Topical Solution for Cats: The most commonly reported adverse reactions include vomiting, hair loss, itching, diarrhea, lethargy, dry skin, elevated ALT, and hypersalivation. BRAVECTO PLUS has not been shown to be effective for 2 months in kittens less than 6 months of age. Use with caution in cats that are heartworm positive. The effectiveness of BRAVECTO PLUS to prevent heartworm disease after bathing or water immersion has not been evaluated.
BRAVECTO has not been shown to be effective for 12-weeks' duration in puppies or kittens less than 6 months of age. BRAVECTO Chews and Topical Solution for dogs is not effective against the lone star tick beyond 8 weeks of dosing. BRAVECTO Topical Solution for Dogs and Cats and BRAVECTO PLUS for cats are for topical use only. Avoid oral ingestion. The safety of BRAVECTO Topical Solution for Cats and BRAVECTO PLUS has not been established in breeding, pregnant, and lactating cats.
All BRAVECTO products contain fluralaner, which is a member of the isoxazoline class. This class has been associated with neurologic adverse reactions including tremors, ataxia, and seizures. Seizures have been reported in dogs receiving isoxazoline class drugs, even in dogs without a history of seizures. Use with caution in dogs with a history of seizures or neurologic disorders. Neurologic adverse reactions have been reported in cats receiving isoxazoline class drugs, even in cats without a history of neurologic disorders. Use with caution in cats with a history of neurologic disorders.
About Merck Animal Health
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than a century, we've been at the forefront of research, bringing forward medicines, vaccines and innovative health solutions for the world's most challenging diseases. Merck Animal Health, a division of Merck & Co., Inc., Rahway, N.J., USA, is the global animal health business of Merck. Through its commitment to The Science of Healthier Animals ® , Merck Animal Health offers veterinarians, farmers, pet owners and governments one of the widest ranges of veterinary pharmaceuticals, vaccines and health management solutions and services as well as an extensive suite of connected technology that includes identification, traceability and monitoring products. Merck Animal Health is dedicated to preserving and improving the health, well-being and performance of animals and the people who care for them. It invests extensively in dynamic and comprehensive R&D resources and a modern, global supply chain. Merck Animal Health is present in more than 50 countries, while its products are available in some 150 markets. For more information, visit www.merck-animal-health.com and connect with us on LinkedIn , Facebook , Twitter and Instagram .
This news release of Merck & Co., Inc., Rahway, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Raghaven et al (Potential Spatial Distribution of the Newly Introduced Long-horned Tick, Haemaphysalis longicornis in North America).
United States Department of Agriculture (USDA) National Haemaphysalis longicornis (Asian longhorned tick) Situation Report.
Laurel Mundth
laurel.mundth@merck.com
Merck Announces KEYNOTE-991 Trial Evaluating KEYTRUDA® Plus Enzalutamide and Androgen Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer to Stop for Futility
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that it will stop the Phase 3 KEYNOTE-991 trial investigating KEYTRUDA, Merck's anti-PD-1 therapy, in combination with enzalutamide and androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Merck is discontinuing the study based on the recommendation of an independent Data Monitoring Committee which reviewed data from a planned interim analysis. At the interim analysis, KEYTRUDA in combination with enzalutamide and ADT did not demonstrate an improvement in overall survival (OS) or radiographic progression-free survival (rPFS), the trial's dual primary endpoints, compared to placebo plus enzalutamide and ADT. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies. No new safety signals were identified; however, the combination was associated with a higher incidence of Grade 3-5 adverse events and serious adverse events compared to the control arm. Merck is informing study investigators of the decision and advises patients in the study to speak to their physician regarding treatment. Data from this study will be presented at an upcoming medical meeting.
"There is a significant unmet need for patients with advanced prostate cancer, and the outcome of this study is an important reminder that this disease remains very difficult to treat," said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. "We are grateful to the patients and investigators for their participation in this study, and we will continue to advance our clinical development program to evaluate KEYTRUDA-based combinations and novel candidates for patients with prostate cancer."
Merck has a strong commitment to the development of new treatment options for patients with prostate cancer. Merck's clinical development program is evaluating KEYTRUDA as monotherapy and in combination with other anti-cancer therapies in the Phase 2 trials KEYNOTE-199 and KEYNOTE-365 and the Phase 3 registrational trial KEYNOTE-641. Additionally, in July 2022, Merck entered into a global development and commercialization agreement with Orion Corporation for Orion's investigational candidate ODM-208 (MK-5684), which is currently being evaluated in a Phase 2 clinical trial for the treatment of patients with metastatic castration-resistant prostate cancer.
About KEYNOTE-991
KEYNOTE-991 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04191096 ) evaluating KEYTRUDA in combination with enzalutamide plus ADT versus placebo in combination with enzalutamide plus ADT in patients with mHSPC. The primary endpoints are OS and rPFS per Prostate Cancer Working Group-modified RECIST v1.1 as assessed by blinded independent central review. Secondary endpoints include objective response rate, duration of response and safety. The trial enrolled 1,251 patients who were randomized to receive KEYTRUDA (200 mg intravenously every three weeks for up to two years) plus enzalutamide (160 mg daily) and ADT (at a dose and frequency of administration that is consistent with the local product label), or placebo plus enzalutamide and ADT.
About metastatic hormone-sensitive prostate cancer
Prostate cancer is the second most common cancer in men globally and is associated with a significant mortality rate, with approximately 375,300 people estimated to have died from the disease in 2020. Up to one-third of patients with prostate cancer will develop metastatic disease, where the cancer has spread to other parts of the body, and face a five-year survival rate of only 30%. The development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. In patients with mHSPC, the cancer can be treated with hormone therapy, also known as ADT, which blocks or stops androgens to slow cancer growth. Despite high initial response rates with ADT alone, the majority of patients progress to castration-resistant prostate cancer within three years and no longer respond to hormone therapy.
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established
Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final dose.
Chrissy Trank
Merck's KEYTRUDA® Plus Chemotherapy Significantly Improved Overall Survival Versus Chemotherapy in First-Line Advanced or Unresectable Biliary Tract Cancer in KEYNOTE-966 Trial
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced positive results from the Phase 3 KEYNOTE-966 trial. In the final analysis of this trial, KEYTRUDA, Merck's anti-PD-1 therapy, in combination with standard of care chemotherapy (gemcitabine and cisplatin) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus chemotherapy alone for the first-line treatment of patients with advanced or unresectable biliary tract cancer (BTC). The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies. Results will be presented at an upcoming medical meeting and will be submitted to regulatory authorities.
"Biliary tract cancer is typically diagnosed at an advanced stage, and these patients face a poor prognosis, with five-year survival rates estimated to be approximately 5% to 15%," said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. "We are very encouraged by these overall survival results that show the potential benefit of KEYTRUDA in addition to chemotherapy for biliary cancer patients who are in urgent need of new treatment options."
Merck has an extensive clinical development program evaluating KEYTRUDA in gastrointestinal cancers and is continuing to study KEYTRUDA for multiple uses in gastric, hepatobiliary, esophageal, pancreatic and colorectal cancers.
KEYNOTE-966 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04003636 ) evaluating KEYTRUDA in combination with gemcitabine and cisplatin compared to placebo plus gemcitabine and cisplatin for the first-line treatment of advanced and/or unresectable BTC. The primary endpoint was OS, and the secondary endpoints included progression-free survival, objective response rate, duration of response and safety. The trial enrolled 1,069 patients who were randomized to receive KEYTRUDA (200 mg every three weeks for up to approximately two years) plus gemcitabine and cisplatin, or placebo plus gemcitabine and cisplatin.
About Biliary Tract Cancer (BTC)
Biliary tract cancer is a group of rare and highly aggressive cancers in the gallbladder and bile ducts. Biliary tract cancer is the second most common type of primary liver cancer after hepatocellular carcinoma, accounting for 15% of all liver cancers. It is estimated there are approximately 211,000 new cases of BTC diagnosed and 174,000 deaths from the disease each year globally. Biliary tract cancer is most frequently diagnosed in patients between 50 to 70 years old, and 70% of BTC patients are diagnosed at an advanced stage. Patients diagnosed with BTC face a very poor prognosis, as the five-year survival rate is estimated to be between 5% and 15%.
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
John Infanti
Bryan Mc Govern
Pharma Market Forecast: 3 Top Trends That Will Affect Pharma in 2023
Will the pharmaceutical market reestablish itself as a safe option for investors in the new year?
Pharma investments have been disappointing in the recent past, but some experts believe the sector will start down the road to recovery in 2023. Read on to learn about the trends that will drive the industry in the next 12 months.
1. Pharma fundamentals strong, but recovery may take time
Like other industries, pharma faced financial frustrations and diminishing returns in 2022.
The ongoing effects of the COVID-19 pandemic, as well as ongoing pressure from Russia's invasion of Ukraine, weighed on progress in the overall stock market and dampened the pharma sector's performance.
It's clear that investors haven't had much to celebrate lately. How likely is that to change in 2023?
Encouragingly, experts continue to point to the strength of the pharma industry. "We cannot lose sight, especially in the life science sector, of the fact that the industry fundamentals are very strong. It will just take a matter of time before things get back to normality," Subin Baral, EY's global life science deals leader, told Pharmaceutical Technology.
Raj Lala, president and CEO of Evolve Funds, told the Investing News Network that Big Pharma generated significant revenue lines in 2022 thanks to vaccine production as the world continued to contend with COVID-19.
"Some healthcare companies lagged as non-emergency surgeries and procedures were delayed," Lala said. "With the pandemic slowly moving behind us, the rescheduling of some of these elective procedures has helped the sector."
In 2023, pharma stocks will also be affected by US politics. Given the split in Congress after last year's midterm elections, it will be essential for investors to follow discussions on how pharma stocks may be impacted by the Inflation Reduction Act.
"The fallout of the (Inflation Reduction Act) remains hard to predict, and figuring out its longer term implications will be a big focus in 2023," a report published by Evaluate Vantage indicates.
So far in 2023, early returns show names in the pharma sector struggling, at least for now.
2. M&A in the pharma sector looking strong in 2023
According to PwC researchers, mergers and acquisitions in the pharma space and other life science subsectors are expected to reach a collective value of US$225 billion to US$275 billion in 2023.
"Ample corporate cash, the need to continue to invest to address medium-term pipeline gaps and the resetting of biotech valuations will provide the backdrop for an active year," said Roel van den Akker, the firm's pharma and life science deals leader.
This activity will come after uncertainty ruled the sector in 2022, causing pharma deals to fall off during the year.
This year, individual transactions are expected to range from US$5 billion to US$15 billion.
However, PwC is also projecting one or two US$20 billion to US$40 billion deals "in the latter half of 2023 as companies gain more comfort around the (US) Federal Trade Commission's posture in a period of divided government for the next few years."
3. Drugs set to move the needle in 2023
According to Evaluate Vantage, investors should expect vaccines and monoclonal antibodies to lead 2023 revenue generation in the pharma market. The following drugs are expected to be the biggest sellers of the year:
Keytruda from Merck (NYSE:MRK) at nearly US$25 billion.
Comirnaty from Pfizer (NYSE:PFE) and BioNTech (NASDAQ:BNTX) at nearly US$20 billion.
Humira from Abbvie (NYSE:ABBV) and Eisai (OTC Pink:ESALF,TSE:4523) at nearly US$15 billion.
COVID-19 vaccines such as Comirnaty will continue to be some of the biggest money makers for the market, but there will still be uncertainty as to how the virus may change.
"Much still depends on what the virus does in the coming months or years, in terms of rendering existing treatments ineffective," states Evaluate Vantage in its report.
Investor takeaway
The pharma world offers investors a vast set of opportunities, with options for those who want to take risks or make safer bets. In 2023, investors will have to be vigilant and keep an eye on how exterior forces affect market health and sentiment.
Don't forget to follow @INN_LifeScience for real-time updates!
Securities Disclosure: I, Bryan Mc Govern, hold no direct investment interest in any company mentioned in this article.
Merck Announces Second-Quarter 2023 Dividend
Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the Board of Directors has declared a quarterly dividend of $0.73 per share of the company's common stock for the second quarter of 2023. Payment will be made on April 10, 2023, to shareholders of record at the close of business on March 15, 2023.
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter Facebook Instagram YouTube and LinkedIn .
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Michael Levey
Steven Graziano
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