Regulatory Decision Summary for Revolade

In consideration of the proposed expansion of the indication for the treatment of chronic ITP in adults, relevant clinical efficacy data from two phase III studiesTRA100773B, and TRA102537/RAISE, previously reviewed with the initial Revolade submission, as well as final data from Study TRA105325 (EXTEND) were reviewed.

In TRA100773B and RAISE, Revolade or placebo was administered once daily for up to six weeks and six months, respectively, to adults with chronic ITP. Across these studies nearly two-thirds of subjects in each treatment group were not splenectomized. Longer-term efficacy results from RAISE confirmed short-term efficacy results from TRA100773B. Collectively, TRA100773B and RAISE demonstrated the superiority of Revolade to placebo in achieving a platelet response (≥50 x 10⁹/L) in adults with chronic ITP who had received one or more prior ITP therapies, regardless of baseline splenectomy status. In RAISE, the odds of achieving a response in Revolade-treated subjects were eight times greater than in placebo-treated subjects. There was an increase in the overall incidence of adverse events (AEs) and treatment-related AEs, but no increase in overall incidence of deaths, serious AEs (SAEs) or withdrawals due to AEs. There was no meaningful difference observed in the safety profile between splenectomized and non-splenectomized subjects.

Study EXTEND was a single arm, open-label study designed primarily to assess the safety of Revolade over long-term dosing in adults with previously treated chronic ITP of at least six months duration. Eligible subjects were previously enrolled in a Revolade study but could have received either placebo or Revolade. Efficacy parameters were secondary endpoints. This extension study contributed supportive data to the initial submission. At this final analysis, 302 subjects, 62% of whom were not splenectomized at baseline, had received a median daily dose of 51 mg with a median duration of exposure of 865 days. One hundred and eighty subjects had completed >2 years of treatment. Revolade was well-tolerated with long-term dosing. No new safety signals were identified. Most toxicities were predictable and manageable with standard treatments. Few AEs led to permanent discontinuation from study medication. Overall, safety data reflected the known safety profile, regardless of splenectomy status. Regardless of duration of exposure, more splenectomized subjects experienced AEs and SAEs compared with non-splenectomized subjects. Efficacy data were supportive of efficacy results in the previously reviewed Phase III short- and medium-term studies, regardless of splenectomy status.

Revolade continues to show a positive benefit-risk relationship for the treatment of adult patients with chronic ITP, and has been shown to be a safe and effective treatment option to increase platelet counts in non-splenectomized patients, if clinically indicated. The safety and efficacy results from the extension study provide reassurance for the continuance of therapy beyond one year, if clinically indicated. The established recommendation to monitor platelet count throughout therapy serves to further mitigate risk of loss of efficacy with long-term dosing.