|Drug class||Complement inhibitor|
|Main uses||Prevent angioedema in hereditary angioedema|
|Side effects||Pain at the site of injection, upper respiratory infection, headache, rash, muscle pain, dizziness, diarrhea|
|Chemical and physical data|
|Molar mass||145684.18 g·mol−1|
Lanadelumab, sold under the trade name Takhzyro, is a medication used to prevent angioedema in people with hereditary angioedema. It is given by injection under the skin. It is used in people over the age of 12.
Common side effects include pain at the site of injection, upper respiratory infection, headache, rash, muscle pain, dizziness, and diarrhea. Other side effects may include allergic reactions. Safety in pregnancy is unclear. It is a monoclonal antibody that attaches to and blocks kallikrein (pKal).
Lanadelumab was approved for medical use in the United States and Europe in 2018. In the United States it costs about 685,000 USD per person per year when given every two weeks. In the United Kingdom this amount costs the NHS about £350,000.
It is used for people 12 years and older for the prevention of hereditary angioedema (HAE) attacks. There is no data on the efficacy or safety under the age of 12 years old. Lanadelumab was not studied in pregnant or breastfeeding women.
Evidence has found attacks decreased from 2 a month to 0.3 to 0.5 per month.
- Injection site pain in 43%
- Viral upper respiratory tract infection in 24%
- Headache in 20%
- Injection site erythema in 95%
- Injection site bruising in 7%
- Dizziness in 6%
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.
Hereditary angioedema (HAE) occurs 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.
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. Lanadelumab’s 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.
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.
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