Treatment with the oral Syk inhibitor fostamatinib led to "markedly improved" hemoglobin (Hb) levels in patients with warm autoimmune hemolytic anemia (wAIHA), according to updates from a phase II and III trial presented at the 2020 ASH Annual Meeting. Lead author Nichola Cooper, MD, from Imperial College London in the U.K., shared these results in a poster presentation.
"There are currently no approved treatments for wAIHA," Dr. Cooper noted. But, "we know that fostamatinib works in immune thrombocytopenia, so we're hopeful that this would be a very targeted treatment for these patients with a rare condition that is very frustrating to treat."
Dr. Cooper provided an update from the phase II, open-label, multicenter study that enrolled 25 patients with wAIHA. Participants received fostamatinib 150 mg twice daily for 24 weeks. Efficacy endpoints included an Hb response (defined as Hb level â‰¥10 g/dL with a â‰¥2 g/dL increase from baseline in the absence of rescue therapy), the duration of Hb response, and the need for wAIHA rescue treatment.
Almost half of patients (n=12; 48%) responded to treatment – including 11 who responded by week 24 and another patient who responded at week 30.
Increases in median Hb were generally detected in week two and sustained over time, Dr. Cooper reported. Six participants received rescue therapy, which included red blood cell transfusion, prednisone, or immunoglobulins. Investigators found that patients with secondary wAIHA appeared to have better response rates than those with primary wAIHA (4 of 5 patients vs. 7 of 19 patients, respectively), as did patients who received fostamatinib as a second-line therapy as opposed to a third-line or later therapy (67% vs. 33%). Women also appeared to respond better than men, but it is difficult to draw conclusions from this small patient population, Dr. Cooper noted.
She also shared findings from the ongoing phase III, double-blind, randomized, placebo-controlled trial evaluating fostamatinib. As of the July 2020 data cutoff, 43 participants had been randomized 1:1 to receive either fostamatinib (100 or 150 mg twice-daily) or placebo.
Seventeen participants had completed 24 weeks of treatment and were rolled over into the open-label extension study. In the phase III trial, patients' median age was 61 years, and most (88%) had primary wAIHA. At baseline, the median Hb was 8.6 g/dL (range = 5.8-11.2 g/dL).
Adverse events (AEs) across both trials were manageable, consistent with those observed in the fostamatinib safety database of more than 4,000 patients across multiple diseases. However, 46% of patients included in the phase II safety analysis experienced a severe AE. The most common AEs included diarrhea, fatigue, and hypertension.
The phase III trial is ongoing, and Dr. Cooper noted that a total of 90 patients are planned for enrollment, which is expected to be completed later this year.
Study authors report relationships with Rigel Pharmaceuticals, which manufactures fostamatinib.
Cooper N, Numerof RP, Tong S, Kuter DJ. Fostamatinib for the treatment of warm antibody autoimmune hemolytic anemia (wAIHA): a phase 3, randomized, double-blind, placebo-controlled, global study. Abstract #752. Presented at the 2020 American Society of Hematology Annual Meeting, December 5, 2020.