Takeda's anti-CD38 antibody advances to phase 3 after increasing platelet count in bleeding disorder

Takeda recently presented promising phase 2 data for their anti-CD38 antibody, mezagitamab, at the International Society on Thrombosis and Haemostasis Congress. The data suggests that mezagitamab could potentially revolutionize the treatment of primary immune thrombocytopenia (ITP), despite the company’s recent decision to deprioritize its development for other conditions such as myasthenia gravis and systemic lupus erythematosus.

Takeda’s phase 2b trial, involving 41 patients, evaluated three different doses of mezagitamab for ITP, an immune-mediated disorder characterized by the accelerated destruction of platelets, leading to reduced platelet counts and increased bleeding. The trial primarily focused on the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) causing discontinuation of treatment.

The results demonstrated that mezagitamab had a favorable safety profile, with no new safety concerns identified. The discontinuation rate due to TEAEs was 14.3% across all dose groups, compared to 0% in the placebo group. Additionally, the incidence of grade 3 or higher TEAEs was 17.9% in the mezagitamab groups and 23.1% in the placebo group. SAEs were reported in 14.3% of mezagitamab patients versus 7.7% of placebo patients.

All three doses of mezagitamab significantly improved platelet response compared to placebo, with rapid and sustained increases in platelet counts above the therapeutic threshold of 50,000/μL. These elevated platelet levels persisted for eight weeks following an eight-week course of weekly dosing, highlighting the medication's lasting effects post-treatment.

Particularly noteworthy were the outcomes for patients receiving the highest dose of 600 mg. In this group, there was an 81.8% complete platelet response, a 90.9% clinically meaningful platelet response, and a 100% hemostatic platelet response, indicating strong efficacy.

Currently, drugs like Novartis’ Promacta, Amgen’s Nplate, and Sobi’s Doptelet are approved treatments for ITP. Meanwhile, Argenx’s FcRn drug Vyvgart failed to meet its primary and secondary endpoints in a phase 3 study in November 2023 aimed at treating the condition.

Takeda highlighted a significant unmet need in the treatment of ITP, noting that around 20% of patients fail to achieve a platelet count above 50,000/μL despite existing first- and second-line therapies. This benchmark of maintaining a platelet count of 50,000/μL or higher over a sustained period has become crucial for new drug approvals in this therapeutic area.

David Kuter, M.D., who presented the findings, emphasized the persistent disease burden and the necessity for a tolerable, disease-modifying treatment for patients living with ITP. He noted that despite the availability of current therapies, there remains a substantial need for new treatments that can provide better outcomes for patients.