Sanofi revealed that its investigational BTK inhibitor rilzabrutinib notched a significant win in the LUNA 3 phase 3 study, hitting the primary endpoint of durable platelet response in adults with persistent or chronic immune thrombocytopenia (ITP). The study showed a significantly higher proportion of rilzabrutinib-treated patients achieved the platelet response goal compared to placebo in this difficult-to-treat ITP population.
“The LUNA 3 results reinforce rilzabrutinib’s potential to provide clinically meaningful benefits for people living with severe immune diseases like ITP,” said Houman Ashrafian, Sanofi’s head of R&D. The company expects to file regulatory submissions for rilzabrutinib in the U.S. and EU by year-end.
Rilzabrutinib received Fast Track Designation from FDA for ITP in November 2020 and also previously won Orphan Drug Designation.
The small molecule became part of Sanofi’s pipeline in 2020 via its $3.6 billion Principia’s acquisition.
An earlier Phase 1/2 study (NCT03395210) focused on rilzabrutinib in ITP has explored the role of cognitive impairment involved in the disease.
A selective BTK inhibitor
Rilzabrutinib is a small-molecule compound designed to selectively inhibit Bruton’s tyrosine kinase (BTK), a crucial enzyme in the B-cell receptor signaling pathway. This pathway is involved in the development and functioning of B cells.
By inhibiting BTK, rilzabrutinib can effectively disrupt the signaling cascades that contribute to the abnormal growth and survival of B cells. This mechanism of action makes rilzabrutinib a promising therapeutic candidate for treating various diseases characterized by dysregulated B-cell activity, such as certain autoimmune disorders and types of lymphoma.
Earlier, rilzabrutinib missed primary endpoint in dermatologic autoimmune diseases
Sanofi’s investigational BTK inhibitor rilzabrutinib has seen contrasting clinical results in recent years. In the PEGASUS phase 3 trial in pemphigus vulgaris and pemphigus foliaceus evaluating rilzabrutinib plus low-dose corticosteroids, there was no significant difference versus placebo in achieving complete remission during the primary analysis period.
Key secondary endpoints such as cumulative corticosteroid dose and duration of remission also did not favor the rilzabrutinib combination over placebo. While a subgroup showed higher remission rates with rilzabrutinib plus very low-dose steroids, the overall results were a setback for the program.
Sanofi is exploring the potential of rilzabrutinib across a range of immune-mediated diseases. The drug candidate will be the focus of phase 3 trials for chronic spontaneous urticaria and prurigo nodularis. Additional phase 2b data readouts are anticipated in the second half of 2024 for IgG4-related disease and warm autoimmune hemolytic anemia. An ongoing phase 2 study is evaluating rilzabrutinib in asthma as well.
Beyond rilzabrutinib, the company has more than a dozen potential new medicines spanning areas such as asthma, urticaria and IgG4-related diseases.
Filed Under: Hematology, Immunology, Orphan Drugs, Rare disease
