Sanofi Seeks Approval for BTK Inhibitor Rilzabrutinib

According to a recent announcement by the Center for Drug Evaluation (CDE) on December 30, Sanofi's application for market authorization of its BTK inhibitor, Rilzabrutinib, has been officially accepted. This development marks a significant step for Sanofi, which has been actively conducting clinical trials in China to explore the drug's effectiveness in treating various autoimmune conditions. Among these efforts is a Phase III study (CTR20220447) targeting immune thrombocytopenia (ITP) and a Phase IIb study (CTR20212864) focusing on warm autoimmune hemolytic anemia.

In April 2024, Sanofi revealed that its Phase III LUNA 3 study had yielded positive outcomes for adult patients suffering from persistent or chronic immune thrombocytopenia (ITP), successfully meeting the primary endpoint. This milestone prompted Sanofi to proceed with the market authorization application for Rilzabrutinib. Should the application be approved, Rilzabrutinib would be the first BTK inhibitor available for the treatment of ITP.

The LUNA 3 study involved a randomized, multicenter, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of Rilzabrutinib, dosed at 400 mg twice daily, compared to a placebo. This trial targeted adult and adolescent patients with persistent or chronic ITP who had previously undergone treatment. The study featured a double-blind treatment phase lasting between 12 to 24 weeks, succeeded by a 28-week open-label treatment period with Rilzabrutinib. It concluded with either a 4-week safety follow-up or transitioned into a long-term extension study.

The primary endpoint focused on the proportion of patients achieving a platelet count of at least 50,000/μL for a minimum of 8 weeks during the final 12 weeks of the 24-week double-blind treatment phase without resorting to rescue therapy. At the study's baseline, patients exhibited an average platelet count of 15,000/μL, whereas the normal range is typically 150,000–450,000/μL.

Results from the study indicated that the Rilzabrutinib group achieved a significantly higher sustained platelet response compared to the placebo group, demonstrating both clinical and statistical relevance. Moreover, the study accomplished its key secondary endpoints. The safety profile of Rilzabrutinib was consistent with outcomes from previous research.

Rilzabrutinib, developed by Principia Biopharma, is an oral, reversible, covalent BTK inhibitor. In August 2020, Sanofi acquired Principia Biopharma for $3.68 billion, thereby gaining access to Rilzabrutinib and several other promising products.

BTK is a crucial protein expressed in B cells, mast cells, and other cells involved in innate immune responses, playing a significant role in the development of various autoimmune diseases. Rilzabrutinib functions by mitigating ITP complications through the reduction of pathogenic autoantibodies and macrophage-mediated platelet destruction.

Immune thrombocytopenia (ITP) is a severe acquired autoimmune hematologic disorder characterized by autoantibody-mediated platelet destruction and compromised platelet production. This results in decreased platelet counts (<100,000/μL), heightening the risk of life-threatening bleeding, such as intracranial hemorrhage. Additionally, ITP negatively affects patients' quality of life, leading to fatigue and cognitive issues.

Beyond the ITP indication, Sanofi is investigating Rilzabrutinib's potential to treat other autoimmune diseases, including IgG4-related disease, warm autoimmune hemolytic anemia, chronic spontaneous urticaria, and prurigo nodularis. This exploration underlines Sanofi’s commitment to advancing treatments for autoimmune disorders, leveraging Rilzabrutinib’s promising therapeutic capabilities.