FDA Grants Rilzabrutinib Fast Track Designation for Immune Thrombocytopenia

The FDA has granted a fast track designation to the BTK inhibitor rilzabrutinib (PRN1008) for the treatment of patients with immune thrombocytopenia (ITP).

“By awarding fast track designation to rilzabrutinib, an investigational candidate for the treatment of ITP, the FDA has recognized rilzabrutinib’s potential to meaningfully improve outcomes for patients with this debilitating disease,” Dolca Thomas, chief medical officer of Principia, a Sanofi company, stated in a press release.

“This is an excellent acknowledgment as we initiate our phase 3 study,” Thomas added. “Fast track designation is designed to facilitate the development and expedite the review of investigational treatments that demonstrate the potential to address unmet needs in serious or life-threatening conditions.”

Rilzabrutinib was designed to possess potential broad utility in immune-mediated diseases and to have an optimized safety and efficacy profile through the use of Principia Biopharma’s Tailored Covalency technology. Because of this technology, the agent should be able to prolong and reverse action at the target site, while being quickly eliminated from the body. Rilzabrutinib was developed to limit its systemic exposure, while could promote fast clinical reversibility of unwanted effects on the immune system.

Results from a phase 1/2 trial indicated that the responses elicited by the agent were durable. Specifically, 50% of patients who were administered the agent at a dose of 400 mg twice daily and had received treatment for at least 12 weeks (n = 26) had achieved the primary end point of having 2 or more consecutive platelet counts, separated by at least 5 days of 50,000/μL or more, and an increase in platelet count of 20,000/μL or more from baseline, without rescue intervention.² Moreover, in the overall patient population (n = 47), 43% met the primary end point, regardless of the dose and duration of treatment.

Of the patients who received 400 mg twice daily, 53% achieved a clinically significant platelet count of 30,000/μL or more on day 8. Of those who achieved the primary end point, 79% had a platelet count of 30,000/μL or more by day 8; these patients were found to have sustained responses with a platelet count of 50,000/μL or more for 71% of the time. Moreover, responders were reported to have achieved platelet counts of 20,000/μL or more above baseline 88% of the time.

“Rilzabrutinib treatment of 400 mg twice daily led to both a rapid response detectable at the first platelet measurement (day 8), and a durable response, David Kuter, MD, DPhil, the principal investigator of the trial and the director of Clinical Hematology at Massachusetts General Hospital, had commented at the time. “These results are significant not only for the speed of onset and sustainability of response, but also for the heavily pretreated nature of the population in which the results were seen.”

Rilzabrutinib is under examination in a double-blind, randomized phase 3 trial (NCT04562766) in adults and adolescent patients with persistent or chronic ITP with an average platelet count of less than 30,000/μL on 2 counts at least 5 days apart in the 14 days before treatment initiation. In the trial, patients will be administered the agent at a dose of 400 mg twice daily.³

The oral, reversible covalent, BTK inhibitor is also under investigation in a phase 3 trial (NCT03762265) for patients with pemphigus, and in a phase 2 trial (NCT04520451) as a potential treatment for patients with autoimmune condition IgG4 disease.

References

1. Rilzabrutinib granted FDA fast track designation for treatment of immune thrombocytopenia. News release. Sanofi. November 18, 2020. Accessed November 18, 2020. https://bit.ly/3lKOEyx.
2. Principia presents updated positive data of rilzabrutinib for immune thrombocytopenia in ongoing phase 1/2 trial. News release. Principia Biopharma, Inc. June 12, 2020. Accessed November 18, 2020. https://bit.ly/36QKMpH.
3. Study to evaluate rilzabrutinib in adults and adolescents with persistent or chronic immune thrombocytopenia (ITP) (LUNA). ClinicalTrials.gov. Updated November 12, 2020. Accessed November 18, 2020. https://clinicaltrials.gov/ct2/show/NCT04562766