Melphalan flufenamide, sold under the brand name Pepaxto, is an anticancer medication used to treat multiple myeloma.The most common adverse reactions include fatigue, nausea, diarrhea, pyrexia and respiratory tract infection.Melphalan flufenamide is a peptidase enhanced cytotoxic (PEnC) that exerts a targeted delivery of melphalan in cells with high expression of aminopeptidases, such as aminopeptidase N, which has been described as over-expressed in human malignancies. Aminopeptidase N plays a functional role in malignant angiogenesis.Melphalan flufenamide was approved for medical use in the United States in February 2021. Medical uses
Melphalan flufenamide is indicated in combination with dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma, with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD-38 directed monoclonal antibody. Metabolism
Melphalan flufenamide is metabolized by aminopeptidase hydrolysis and by spontaneous hydrolysis on N-mustard. Its biological half-life is 10 minutes in vitro. Origin and development
Melphalan flufenamide is a peptidase enhanced cytotoxic (PEnC) with a targeted delivery within tumor cells of melphalan, a widely used classical chemotherapeutic belonging to a group of alkylating agents developed more than 50 years ago. Substantial clinical experience has been accumulated about melphalan since then. Numerous derivatives of melphalan, designed to increase the activity or selectivity, have been developed and investigated in vitro or in animal models. Melphalan flufenamide was synthesized, partly due to previous experience of an alkylating peptide cocktail named Peptichemio and its anti-tumor activity is being investigated.
The ballot measure eventually failed to pass, losing 51.32% to 48.68%. Litigation and bankruptcy
In December 2016, seven former executives and managers employed by Insys were taken into custody, including CEO John Kapoor and charged with conspiracy to bribe medical staff in several states to prescribe a specific pain medication to their patients. The accusations were the topic of an NBC special feature report on Megyn Kellys Sunday Night on June 4, 2017.In August 2017, Insys Therapeutics was sued by Arizona Attorney General Mark Brnovich for misleading patients and doctors about the dangers of the drug Subsys, and for lying to insurers about the condition of the patients in a bid to get payment for the drug. He said the firm deceived insurers and pharmaceutical benefit companies into agreeing to pay for the expensive drug by misleading them to believe that the payment request was coming from a doctors office and not the company making the drug. Brnovich also said those Insys employees misrepresented the medical conditions of the patients, lying that they had breakthrough pain, lying that the patients had tried other medications, and lying that the patients needed the sublingual spray rather than less expensive pills marketed by other firms because they had difficulty swallowing. Insys Therapeutics issued a response to the Arizona filing on their website, stating, in part, that "[t]he allegations contained in the Arizona Attorney Generals complaint relate to former employees and physicians that are no longer associated with our Company or our speaker bureau.