Mibavademab

What is mibavademab?

Mibavademab (also known as REGN4461) is an investigational protein-based medicine. It is being developed by Regeneron Pharmaceuticals, Inc. and does not yet have a marketing authorisation, meaning it is not approved as a medicine for routine use.^[1] The substance is classified in the hormonal diseases area of the registry, and its pharmaceutical form in the trials is a solution for injection.^[1]

Mibavademab acts as a leptin receptor agonist, which means it attaches to and activates the same receptor in the body that the natural hormone leptin normally activates.^[3]

How does mibavademab work?

Leptin is a hormone that helps regulate body weight and metabolism. In some rare conditions, the body does not produce enough working leptin or cannot respond to it properly. Mibavademab is designed to mimic the action of leptin by binding to the leptin receptor. This activation is intended to help restore the signalling that leptin would normally provide.^[3] A first-in-human Phase 1 study has already examined how mibavademab behaves in the body, including its pharmacokinetics (how the drug is absorbed, distributed and cleared) and pharmacodynamics (the effects it has on the body).^[3]

Which conditions is mibavademab studied for?

• Monogenic obesity — a rare form of obesity caused by changes in a single gene, in this case the leptin (LEP) gene. The trial includes children, adolescents and adults.^[1]
• Generalized lipodystrophy — a rare condition in which the body has very little fat tissue, leading to metabolic problems such as high blood sugar and high triglycerides. The trial includes adults and children.^[2]

How is mibavademab given?

Mibavademab is prepared as a solution for injection. In the registered trials it may be administered by intravenous, subcutaneous or intramuscular routes, meaning into a vein, under the skin, or into a muscle.^[1]

What do the clinical trials show?

Two Phase 3 trials of mibavademab are registered in the EU Clinical Trials Information System. Both are currently authorised, meaning they have received approval to proceed. Because these are ongoing Phase 3 studies, results are not yet available; the trials are designed to measure specific outcomes.

What are the trials measuring?

In the monogenic obesity trial, the primary outcome is the percent change in Body Mass Index (BMI) from the start of treatment to week 24.^[1] In the generalized lipodystrophy trial, Part A will assess the effect of mibavademab on HbA1c (a measure of long-term blood sugar control) and triglyceride (TG) levels, while Part B will evaluate safety, tolerability and how much of the drug remains in the blood over time (pharmacokinetics, or PK).^[2]

Who can take part in these trials?

The monogenic obesity trial includes children, adolescents and adults with obesity due to leptin gene mutations, with a planned enrollment of 5 participants.^[1] The generalized lipodystrophy trial includes adult and paediatric patients, with a planned enrollment of 28 participants.^[2]

What side effects are known?

The Phase 1 study provides information on how mibavademab behaves in the body, but the available source does not list specific side effects in a grouped way. Detailed safety information from the ongoing Phase 3 trials is not yet available.