Repositioning Candidate Details
| Candidate ID: | R1533 |
| Source ID: | DB14597 |
| Source Type: | approved; investigational |
| Compound Type: | biotech |
| Compound Name: | Lanadelumab |
| Synonyms: | Lanadelumab; lanadelumab-flyo |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | 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. |
| CAS Number: | 1426055-14-2 |
| Molecular Weight: | |
| DrugBank Indication: | 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. |
| DrugBank Pharmacology: | 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%. In phase 3 clinical trials (HELP study, lanadelumab showed an attack rate reduction of over 70% for all three different dose regimes. |
| DrugBank MoA: | 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. |
| Targets: | Plasma kallikrein inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
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