| 2019-06-03 08:38:10|
FTSV 08:38 06/03 06/03/19
Forty Seven announces updated data on 5F9 with azacitidine trial at ASCO
Forty Seven announced updated initial data from its Phase 1b clinical trial evaluating 5F9 as a monotherapy and in combination with azacitidine for the treatment of myelodysplastic syndrome, or MDS and acute myeloid leukemia, or AML. The data, which have matured since the abstract submission and now include additional patients and longer-term follow-up, will be presented in a poster discussion session at ASCO. Forty Seven's Phase 1b trial, which is being funded in part by the California Institute for Regenerative Medicine, or CIRM, is designed to evaluate 5F9 as a monotherapy in patients with relapsed or refractory MDS or AML, and 5F9 in combination with azacitidine in higher-risk MDS patients and untreated, induction chemotherapy-ineligible AML patients. All patients received a 1 mg/kg priming dose of 5F9, coupled with intrapatient dose escalation, to mitigate on-target anemia. Patients in the combination cohort were then treated with full doses of azacitidine and a 5F9 maintenance dose of 30 mg/kg once weekly. As of the data cutoff of May 10, 46 patients had been treated in the Phase 1b portion of the trial, including 10 r/r MDS or AML patients who received monotherapy 5F9, and 36 untreated higher-risk MDS patients or untreated AML patients ineligible for induction chemotherapy, who received 5F9 in combination with azacitidine. As of the data cutoff, 5F9 was well-tolerated both as a monotherapy and in combination with azacitidine, with no evidence of increased toxicities compared to azacitidine alone. Adverse events, or AEs, were consistent with what has been previously seen with 5F9, and no significant cytopenias or autoimmune-related AEs were observed in patients treated with monotherapy 5F9. Overall, the most commonly reported treatment-related AEs were expected CD47-mechanism-based effects on red blood cells, which led to a temporary and reversible anemia, and many patients in the combination cohort experienced a hemoglobin improvement over the course of their treatment with a decrease in transfusions. Importantly, no treatment-related infections were observed, and only one patient out of 36 treated with the combination experienced neutropenic fever. No deaths were observed in the first 60 days on combination treatment. Only one patient out of 46 discontinued treatment due to a treatment-related AE. As of the data cutoff, 35 patients were evaluable for response assessment, including 25 patients with untreated higher-risk MDS or AML who were treated with 5F9 and azacitidine and 10 patients with r/r MDS or AML who were treated with monotherapy 5F9. In higher-risk MDS, the overall response rate, or ORR, for the combination was 100%, with six patients achieving a complete response, or CR, four patients achieving a marrow CR and one patient achieving hematologic improvement. In untreated AML, the ORR for the combination was 64%, with five patients achieving a CR, two patients achieving a complete response with incomplete blood count recovery and two patients achieving a morphologic leukemia-free state. Additionally, five patients achieved stable disease. In r/r MDS or AML treated with monotherapy 5F9, the ORR was 10%, consisting of one patient who achieved a MLFS. Additionally, seven patients achieved SD. The median time to response among MDS and AML patients treated with the combination was 1.9 months. Six patients receiving the combination who had an objective response have experienced deepening responses over time resulting in complete remissions. Five patients have also successfully received allogeneic stem cell transplants. Historical response rates for single-agent azacitidine, show CR rates of approximately 15%-20% in higher-risk MDS and untreated AML patients, with initial responses generally occurring after 4-6 months in most patients who respond. Based on the safety profile and clinical activity observed in this Phase 1b clinical trial to-date, expansion cohorts have been initiated in patients with both higher-risk MDS and untreated AML with 5F9 in combination with azacitidine. Additionally, based on feedback from a Type B meeting with the FDA in May, Forty Seven believes that data from a single arm pivotal study evaluating durability, CRs and partial responses may be sufficient to support the registration of 5F9 in combination with azacitidine in patients with untreated, higher-risk MDS. The company is currently finalizing the operational components of the proposed registrational study, including details on trial design and chemistry, manufacturing and controls and will provide a detailed update in the second half of 2019.