FDA Grants Fast Track Designation to Rilzabrutinib for Treatment of Immune Thrombocytopenia

The FDA has granted a Fast Track designation to rilzabrutinib, an oral investigational Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of immune thrombocytopenia. The drug was previously granted Orphan Drug designation for this indication.¹

"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. This is an excellent acknowledgment as we initiate our Phase 3 study,” said Dolca Thomas, chief medical officer of Principia, a Sanofi company, in a statement. “Fast Track Designation is designed to facilitate the development and expedite the review of investigational treatments that demonstrate the potential to address unmet medical needs in serious or life-threatening conditions.”

It was previously reported, during the European Hematology Association (EHA) Virtual Annual Congress, that rilzabrutinib induced durable responses in patients with immune thrombocytopenia in a phase 1/2 study. The study included 47 heavily-pretreated patients who had a median of 6 prior therapies. The study subjects were followed for 18 weeks on treatment with rilzabrutinib.²

The primary end point of the study was the proportion of patients able to achieve 2 or more consecutive platelet counts, separated by at least 5 days of ≥ 50,000/μL and an increase of platelet count of ≥20,000/μL from baseline, without the use of rescue medication.

Results from the study show that 50% (80% CI, 38-62) of the population achieved the primary end point after 12 weeks of treatment with the 400 mg dose of rilzabrutinib. Irrespective of dose and treatment duration, 43% (80% CI, 34-52), of the overall population of patients in the study achieved the primary end point.

Platelet count in the population of patients treated with rilzabrutinib 400 mg was ≥30,000/µLin 53% of patients on day 8, demonstrating clinical significance. Among those who achieved the primary end point, 79% had a platelet count ≥30,000/µL by day 8. Notably, a platelet count of ≥50,000/µLwas sustained in these patients 71% of the time. Finally, responders to rilzabrutinib had a platelet count of ≥20,000/µL above baseline 88% of the time.

As a single agent, rilzabrutinib was well-tolerated in patients, and toxicities were manageable with thrombopoietin receptor agonists and corticosteroids. There were no treatment-related bleeding or thrombotic events reported in this study. Treatment-emergent adverse events were reported in 21 patients (45%) but were all low grade.

Findings from rilzabrutinib as treatment of immune thrombocytopenia will be confirmed in the pivotal phase 3 clinical trial that Sanofi plans to initiate.^1,2

_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/3nz7EjX}

_{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/3nASBGF}