Rigel Reports Late Stage Trial Failure of Fostamatinib in Rare Bleeding Disorder

Rare Daily Staff

Rigel Pharmaceuticals said top-line efficacy and safety data from the FORWARD phase 3 clinical trial of fostamatinib in patients with warm autoimmune hemolytic anemia did not demonstrate statistical significance in the primary efficacy endpoint of durable hemoglobin response in the overall study population.

Autoimmune hemolytic anemia (AIHA) is a rare, serious blood disorder in which the immune system produces antibodies that lead to the destruction of the body’s own red blood cells. Warm antibody AIHA (wAIHA), which is the most common form of AIHA, is characterized by the presence of antibodies that react with the red blood cell surface at body temperature. wAIHA affects approximately 36,000 adult patients in the U.S. and can be a severe, debilitating disease. To date, there are no disease-targeted therapies approved for wAIHA, despite the unmet medical need that exists for these patients.

In a post-hoc regional analysis of U.S., Canadian, Australian, and Western European trial sites, patients treated with fostamatinib had a favorable durable hemoglobin response compared to placebo, whereas in the Eastern European trial sites patients did not. Rigel plans to continue analyzing the data to understand the geographical differences in patient disease characteristics and outcomes and discuss these findings with the U.S. Food and Drug Administration.

The safety and tolerability profile in the FORWARD trial was consistent with the existing fostamatinib safety database.

“While we are disappointed in the overall results, which were impacted by a large placebo response rate from Eastern European clinical sites, we are encouraged by the top-line results from the U.S., Canada, Australia, and Western Europe. We continue to believe fostamatinib has the potential to benefit patients with wAIHA, a population with a serious unmet medical need,” said Raul Rodriguez, president and CEO of Rigel Pharmaceuticals. “We will continue to analyze the data and look forward to discussing our findings with the FDA.”

Of the 90 patients that completed the FORWARD phase 3 study, 71 (79 percent) enrolled in the open-label extension study. Data from this study will be reported later.

Fostamatinib is currently being evaluated in a phase 3 randomized, double-blind, placebo-controlled clinical study in 90 patients with wAIHA who have failed at least one prior treatment. The study will evaluate the efficacy of fostamatinib versus placebo in achieving a durable hemoglobin response, defined as a hemoglobin level ≥ 10 g/dL, with an increase from baseline level of ≥ 2 g/dL, with the response not being attributed to rescue therapy, and durability measure in hemoglobin on three consecutive available visits during the 24-week treatment period. Secondary endpoints include other measures of hemoglobin response, use of rescue medication, and safety.

The FDA has granted fostamatinib Orphan Drug and Fast Track designations for the treatment of patients with wAIHA. It commercially available in the U.S. under the brand name TAVALISSE as the first and only FDA-approved SYK inhibitor indicated for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to a previous treatment.

Photo: Raul Rodriguez, president and CEO of Rigel Pharmaceuticals