Sanofi Submits Market Authorization Application for BTK Inhibitor Rilzabrutinib

According to information published on the CDE (Center for Drug Evaluation) website on December 30, Sanofi’s market authorization application for its BTK inhibitor Rilzabrutinib has been officially accepted. Sanofi has conducted several clinical trials in China for Rilzabrutinib to treat autoimmune diseases, including a Phase III study (CTR20220447) for immune thrombocytopenia (ITP) and a Phase IIb study (CTR20212864) for warm autoimmune hemolytic anemia.

In April 2024, Sanofi announced that its Phase III LUNA 3 study achieved positive results in treating adult patients with persistent or chronic immune thrombocytopenia (ITP), meeting its primary endpoint. Based on these results, Sanofi planned to submit the market authorization application for Rilzabrutinib. If approved, Rilzabrutinib will become the first BTK inhibitor approved for the ITP indication.

The LUNA 3 study was a randomized, multicenter, double-blind, placebo-controlled clinical trial. It evaluated the efficacy and safety of Rilzabrutinib (400 mg twice daily) versus placebo in treating adult and adolescent patients with persistent or chronic ITP who had previously received treatment. The double-blind treatment phase lasted 12 to 24 weeks, followed by a 28-week open-label treatment period with Rilzabrutinib, and concluded with a 4-week safety follow-up or a long-term extension study.

The primary endpoint of the study was the proportion of patients achieving a platelet count of ≥50,000/μL for at least 8 weeks during the final 12 weeks of the 24-week double-blind treatment phase without requiring rescue therapy. The baseline platelet count of patients in the study was 15,000/μL, while the normal range is 150,000–450,000/μL.

The study results showed that the proportion of patients achieving sustained platelet response was significantly higher in the Rilzabrutinib group compared to the placebo group, with both clinical and statistical significance. Furthermore, the study met its key secondary endpoints. Regarding safety, Rilzabrutinib’s safety profile was consistent with previous studies.

Rilzabrutinib, developed by Principia Biopharma, is an oral, reversible, covalent BTK inhibitor. In August 2020, Sanofi acquired Principia Biopharma for $3.68 billion, gaining access to multiple products, including Rilzabrutinib.

BTK is expressed in B cells, mast cells, and other cells involved in innate immune responses and plays a role in the development of various autoimmune diseases. Rilzabrutinib helps treat ITP complications by reducing the production of pathogenic autoantibodies and macrophage-mediated platelet destruction.

Immune thrombocytopenia (ITP) is a serious acquired autoimmune hematologic disorder characterized by autoantibody-mediated platelet destruction and impaired platelet production, resulting in reduced platelet counts (<100,000/μL) and an increased risk of life-threatening bleeding, such as intracranial hemorrhage. ITP also significantly impacts patients’ quality of life, including fatigue and cognitive dysfunction.

In addition to the ITP indication, Sanofi is exploring Rilzabrutinib’s therapeutic potential for other autoimmune diseases, such as IgG4-related disease, warm autoimmune hemolytic anemia, chronic spontaneous urticaria, and prurigo nodularis.