Sanofi's rilzabrutinib has demonstrated positive results in the LUNA 3 phase 3 study, meeting its primary endpoint of durable platelet response in adult patients with persistent or chronic immune thrombocytopenia (ITP). The study's success underscores the potential of rilzabrutinib as a clinically meaningful treatment option for individuals living with this challenging autoimmune disorder.
The LUNA 3 trial (NCT04562766) was a randomized, multicenter study evaluating the efficacy and safety of rilzabrutinib versus placebo in adult and adolescent patients with persistent or chronic ITP. Participants received either oral rilzabrutinib 400 mg twice daily or placebo during a 12- to 24-week double-blind treatment period, followed by a 28-week open-label treatment and a 4-week safety follow-up. The primary endpoint was defined as the proportion of participants achieving platelet counts at or above 50,000/μL for at least 8 out of the last 12 weeks of the 24-week blinded treatment period, without the need for rescue therapy.
The study included patients with primary ITP who had been refractory to prior therapies, with a median of four prior ITP treatments and a median baseline platelet count of 15,000/μL (normal range: 150,000-450,000/μL). The results showed a statistically significant improvement in the proportion of patients achieving a durable platelet response with rilzabrutinib compared to placebo. Positive results were also observed on key secondary endpoints, further highlighting the potential clinical benefits of rilzabrutinib for ITP patients.
Clinical Significance of Rilzabrutinib in ITP
ITP is a serious autoimmune disorder characterized by autoantibody-mediated platelet destruction and impaired platelet production, leading to thrombocytopenia (low platelet counts below 100,000/μL) and an increased risk of bleeding. Patients often experience fatigue and cognitive dysfunction, significantly impacting their quality of life. Current treatments aim to increase platelet counts but may have limitations or side effects.
Rilzabrutinib, an oral, reversible BTK inhibitor, offers a novel approach by targeting the underlying mechanisms of ITP. By reducing the production of pathogenic autoantibodies and decreasing macrophage-mediated platelet destruction, rilzabrutinib could address a wide range of ITP complications. The drug was granted Fast Track Designation by the FDA in November 2020 and Orphan Drug Designation, highlighting the unmet need for effective ITP treatments.
Sanofi's Commitment to Immunology
"The results of this study reinforce rilzabrutinib’s potential to be a first-in-class oral, reversible BTK inhibitor that can provide clinically meaningful improvements for people living with severe immune-mediated diseases like ITP," said Houman Ashrafian, Executive Vice President, Head of Research and Development, Sanofi. "These pivotal results are a testament to our commitment and expertise in rare blood diseases and ability to build a portfolio of next-generation small-molecule inhibitors that are both more selective and optimized to deliver robust efficacy and safety outcomes as compared to existing therapies."
Sanofi anticipates regulatory submissions in the US and EU by the end of the year. Rilzabrutinib is also being investigated for other immune-mediated diseases, including asthma, chronic spontaneous urticaria, prurigo nodularis, IgG4-related disease, and warm autoimmune hemolytic anemia, showcasing its potential across a broad spectrum of immunological conditions.
