Lanadelumab

Lanadelumab Uses, Dosage, Side Effects, Food Interaction and all others data.

Lanadelumab, also known as DX-2930, is a human IgG1 monoclonal antibody designed for subcutaneous self-injection. It is a fully human immunoglobulin, k-light-chain made in recombinant Chinese Hamster Ovary cells. The FDA and EU granted the designation of priority review, breakthrough therapy and orphan drug for rare diseases based on the results of the reported clinical trials. Lanadelumab was developed by Shire and FDA approved on August 28, 2018.

In phase 1 studies, the level of kininogen, the substrate of kallikrein, was studied as a marker of kallikrein activity. In patients with C1 deficiency, the level of cleaved kininogen is 4-fold higher when compared with C1-normal individuals. When lanadelumab was administered, the levels of cleaved kininogen were significantly reduced with a dose of 300 and 400 mg of lanadelumab with a maximum reduction at day 22 corresponding with time for maximum concentration. This maximum reduction corresponded with the normal levels of cleaved kininogen. Similarly, the decreases of cleaved kininogen corresponded as well with reductions in the levels of the activated factor XII.

Clinically, the attacks of angioedema completely vanished in the patients receiving a dose of 300 mg of lanadelumab. In other doses such as 400 mg and combo 300/400 mg the attack reduction reached 90%.

Lanadelumab
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Lanadelumab
Availability	Prescription only
Generic	Lanadelumab
Lanadelumab Other Names	Lanadelumab, lanadelumab-flyo
Related Drugs	Takhzyro, Orladeyo, Firazyr, Haegarda, Ruconest, Berinert, Cinryze, Kalbitor
Weight	300mg/2ml
Type	Subcutaneous solution
Formula	C₆₄₆₈H₁₀₀₁₆N₁₇₂₈O₂₀₁₂S₄₇
Weight	146000.0 Da
Protein binding	General information on plasma protein binding is not available but it is considered that, as the site of action is with plasma proteins, the percentage of protein binding should be significant.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Lanadelumab is a plasma kallikrein inhibitor used to treat attacks of hereditary angioedema.

Lanadelumab is indicated for the prophylaxis treatment to prevent attacks in patients 12 years and older with hereditary angioedema.

The hereditary angioedema (HEA) is an autosomal dominant disorder resulted from the presence of C1 deficiency. Some reports have indicated a high prevalence of cases that result from spontaneous mutations which can be inherited. This condition is manifested by attacks of subcutaneous or submucosal edema in the face, larynx, GI tract, limbs or genitalia. From all the types of attacks, the most serious is the laryngeal as it can compromise the airway. The rest of the attacks are accompanied by pain and considerable dysfunction.

Lanadelumab is also used to associated treatment for these conditions: Recurrent angiodema, Acute attack of hereditary angioedema

How Lanadelumab works

Lanadelumab is a plasma kallikrein inhibitor. This enzyme works by cleaving high molecular weight kininogen to generate the pro-inflammatory peptide bradykinin which is a potent vasodilator. The activity of plasma kallikrein is regulated by the activity of C1-inhibitor and thus, the patients that are deficient in C1 are known to be correlated to excessive production of bradykinin which will further lead to fatal angioedema. Hence, lanadelumab occludes the proteolytic active site of plasma kallikrein, preventing the cleavage of kininogen to bradykinin. It is a selective inhibitor as it has been reported that lanadelumab does not bind to prekallikrein or to inhibit any other serine proteases. The activity of lanadelumab works as an additional checkpoint for the patients suffering from C1 deficiency.

Toxicity

In clinical trials, the apparition of antidrug antibodies was nos significant and from those who expressed it, none were neutralizing. No significant toxicities related to the administration of lanadelumab have been reported.

Studies regarding the carcinogenic potential or overdosage effect have not been performed. Fertility studies show no effect on reproductive organs.

Volume of Distribution

The reported volume of distribution of lanadelumab is in the range of 12 to 16 L which variates according to the dose administered.

Elimination Route

The drug levels of lanadelumab are dose-dependent and thus, the maximum plasma concentration increased correspondingly with an increased dosage. The Cmax and AUC ranged from 3800 to 45000 ng/ml and from 64000 to 762000 ng.day/ml respectively for concentrations from 30 to 400 mg. As well, sustained quantifiable drug concentration was observed through day 120. The bioavailability of lanadelumab is of approximately 66% with a time to reach peak drug concentration of approximately 7 days.