Lanadelumab
Lanadelumab (INN; trade name Takhzyro) is a human monoclonal antibody (class IgG1 kappa) that targets plasma kallikrein (pKal) in order to promote prevention of angioedema in patients with hereditary angioedema. Lanadelumab, was approved in the United States as the first monoclonal antibody indicated for prophylactic treatment to prevent hereditary angioedema (HAE) attacks. Takhzyro is the first treatment for hereditary angioedema (HEA) prevention made by using cells within a lab, not human plasma. The US Food and Drug Administration approved the use of lanadelumab on 23 August 2018 for patients that are 12 years and older and have either type I or type II hereditary angioedema (HEA). Administration of the medication is done through 1 subcutaneous injection at a dose of 300 milligrams every 2 weeks (every 4-week dosing can be considered in specific patients).In phase 1 clinical trials Lanadelumab was well tolerated and was reported to reduce cleavage of kininogen in the plasma of patients with hereditary angioedema and decrease the number of patients experiencing attacks of angioedema. Lanadelumabs approval in the United States was spearheaded by the data presented in the phase 1b, multicenter, double blind, placebo controlled, multi-ascending-dose trial. Through this trial, Lanadelumab was given Priority Review, Breakthrough Therapy, Orphan Drug designation by the FDA. The phase 3 HELP study evaluated efficacy and safety of lanadelumab. This drug was produced by Dyax Corp and currently under development by Shire.Common side effects include pain associated with injection site reactions, injection site bruising, upper respiratory infection, headache, rash, myalgia, dizziness, and diarrhea.

Medical use
In the United States, lanadelumab is indicated for patients 12 years and older for the prophylaxis of hereditary angioedema (HAE) attacks. There is no data on the efficacy or safety of lanadelumab in patients under the age of 12 years old. Lanadelumab was not studied in pregnant or breastfeeding women.

Adverse events
In a phase 3 randomized controlled trial, which examined the efficacy and safety of lanadelumab in preventing hereditary angioedema attacks, the most common adverse events noted in patients being treated were:
Injection site pain in 42.9% of patients
Viral upper respiratory tract infection in 23.8% of patients
Headache in 20.2% of patients
Injection site erythema in 95% of patients
Injection site bruising in 7.1% of patients
Dizziness in 6.0% of patients

Mechanism of action
Lanadelumab works by binding to an enzyme within the plasma, kallikrein, to inhibit its activity. Kallikrein is a protease that functions to cleave kininogen, subsequently creating kininogen and bradykinin, a potent vasodilator.Patients have hereditary angioedema (HAE) because of a deficiency or dysfunctional C1 inhibitor, which is an enzyme that regulates the activity of the kallikrein-kinin cascade. Poor regulation of the C1 inhibitor results in increased levels of kallikrein and subsequent proteolysis of kininogen. The proteolysis of the kininogen forces an upscaled production of bradykinin and kininogen within the patient. Increased bradykinin levels cause vasodilation, increased vascular permeability, and the succeeding angioedema and pain associated with hereditary angioedema attacks.

Efficacy trial
The phase 3 trial that analyzed the efficacy of lanadelumab is called Effect of Lanadelumab compared with Placebo on Prevention of Hereditary Angioedema Attacks, also known as the HELP study. The objective of the randomized controlled trial was to examine the effectiveness of lanadelumab in preventing hereditary angioedema attacks.
There were 125 patients studied over a 26-week period in the randomized, double-blind, parallel-group, placebo-controlled trial. Patients were randomized to receive either lanadelumab treatment or placebo in a 1:2 ratio. Subjects randomized to receive lanadelumab were further randomized 1:1:1 ratio to receive doses of either 150 mg every 4 weeks, 300 mg every 4 weeks, or 300 mg every 2 weeks. Patients on the medication had a statistically significant reduction in hereditary angioedema attack rates per month.  Patients that took lanadelumab every 2 weeks had 83% less moderate to severe attacks. The study results proved that all three dosing regimens for lanadelumab were more effective than placebo.

References
External links
"Lanadelumab". Drug Information Portal. U.S. National Library of Medicine.