Lanadelumab

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Lanadelumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetKallikrein
Names
Trade namesTakhzyro
Other nameslanadelumab-flyo
Clinical data
Drug classComplement inhibitor[1]
Main usesPrevent angioedema in hereditary angioedema[1]
Side effectsPain at the site of injection, upper respiratory infection, headache, rash, muscle pain, dizziness, diarrhea[1]
Pregnancy
category
  • AU: B1[2]
  • US: N (Not classified yet)[2]
Routes of
use
Subcutaneous
External links
AHFS/Drugs.comMonograph
US NLMLanadelumab
Legal
License data
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU: Rx-only
Chemical and physical data
FormulaC6468H10016N1728O2012S47
Molar mass145684.18 g·mol−1

Lanadelumab, sold under the trade name Takhzyro, is a medication used to prevent angioedema in people with hereditary angioedema.[1] It is given by injection under the skin.[1] It is used in people over the age of 12.[3]

Common side effects include pain at the site of injection, upper respiratory infection, headache, rash, muscle pain, dizziness, and diarrhea.[1] Other side effects may include allergic reactions.[1] Safety in pregnancy is unclear.[1] It is a monoclonal antibody that attaches to and blocks kallikrein (pKal).[1][3]

Lanadelumab was approved for medical use in the United States and Europe in 2018.[1][3] In the United States it costs about 685,000 USD per person per year when given every two weeks.[4] In the United Kingdom this amount costs the NHS about £350,000.[5]

Medical use

It is used for people 12 years and older for the prevention of hereditary angioedema (HAE) attacks.[6][7] There is no data on the efficacy or safety under the age of 12 years old.[8] Lanadelumab was not studied in pregnant or breastfeeding women.[8]

Evidence has found attacks decreased from 2 a month to 0.3 to 0.5 per month.[3]

Dosage

Administration of the medication is done through a subcutaneous injection at a dose of 300 milligrams every 2 weeks (every 4-week dosing can be considered).[6]

Side effects

The most common side effects are:[9][10]

Mechanism of action

Lanadelumab works by binding to an enzyme within the plasma, kallikrein, to inhibit its activity.[11] Kallikrein is a protease that functions to cleave kininogen, subsequently creating kininogen and bradykinin, a potent vasodilator.[11]

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.[12][11] Poor regulation of the C1 inhibitor results in increased levels of kallikrein and subsequent proteolysis of kininogen.[12][11] The proteolysis of the kininogen forces an upscaled production of bradykinin and kininogen within the patient.[12] Increased bradykinin levels cause vasodilation, increased vascular permeability, and the succeeding angioedema and pain associated with hereditary angioedema attacks.[12][11]

Research

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.[12][13][14][15] 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.[12][7] Through this trial, Lanadelumab was given Priority Review, Breakthrough Therapy, Orphan Drug designation by the FDA.[7][16] The phase 3 HELP study evaluated efficacy and safety of lanadelumab. This drug was produced by Dyax Corp and currently under development by Shire.[17]

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.[17][9] Patients were randomized to receive either lanadelumab treatment or placebo in a 1:2 ratio.[17][9] 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.[17][9] Patients on the medication had a statistically significant reduction in hereditary angioedema attack rates per month.[17][9] Patients that took lanadelumab every 2 weeks had 83% less moderate to severe attacks.[8] The study results proved that all three dosing regimens for lanadelumab were more effective than placebo.[17][9]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 "Lanadelumab-flyo Monograph for Professionals". Drugs.com. Retrieved 20 November 2021.
  2. 2.0 2.1 "Lanadelumab (Takhzyro) Use During Pregnancy". Drugs.com. 19 September 2018. Retrieved 4 September 2020.
  3. 3.0 3.1 3.2 3.3 "Takhzyro". Retrieved 20 November 2021.
  4. "Takhzyro Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 20 November 2021.
  5. BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 306. ISBN 978-0857114105.
  6. 6.0 6.1 "HIGHLIGHTS OF PRESCRIBING INFORMATION" (PDF).
  7. 7.0 7.1 7.2 "FDA approves new treatment for rare hereditary disease".
  8. 8.0 8.1 8.2 "www.takhzyro.com".
  9. 9.0 9.1 9.2 9.3 9.4 9.5 "Efficacy and Safety Study of DX-2930 to Prevent Acute Angioedema Attacks in Patients With Type I and Type II HAE".
  10. "Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks A Randomized Clinical Trial". JAMA Network.
  11. 11.0 11.1 11.2 11.3 11.4 "Clinical Pharmacology Database".
  12. 12.0 12.1 12.2 12.3 12.4 12.5 Banerji A, Busse P, Shennak M, Lumry W, Davis-Lorton M, Wedner HJ, et al. (February 2017). "Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis" (PDF). The New England Journal of Medicine. 376 (8): 717–728. doi:10.1056/NEJMoa1605767. hdl:2434/550555. PMID 28225674. S2CID 54486011.
  13. Chyung Y, Vince B, Iarrobino R, Sexton D, Kenniston J, Faucette R, et al. (October 2014). "A phase 1 study investigating DX-2930 in healthy subjects". Annals of Allergy, Asthma & Immunology. 113 (4): 460–6.e2. doi:10.1016/j.anai.2014.05.028. PMID 24980392.
  14. Clinical trial number NCT01923207 for "A Single Increasing Dose Study to Assess Safety and Tolerability of DX-2930 in Healthy Subjects" at ClinicalTrials.gov
  15. Clinical trial number NCT02093923 for "Double-Blind, Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of DX-2930 in Hereditary Angioedema (HAE) Subjects" at ClinicalTrials.gov
  16. "Dyax Corp. Receives FDA Breakthrough Therapy Designation for DX-2930 for Prevention of Attacks of Hereditary Angioedema". www.businesswire.com. Retrieved 2017-03-24.
  17. 17.0 17.1 17.2 17.3 17.4 17.5 "Lanadelumab - Takeda". Adis Insight. Springer Nature Switzerland AG. Retrieved 2017-03-24.

External links

External sites:
Identifiers: