Pfizer Inc. (NYSE: PFE)today announced positive topline results from the Phase 3 BASIS study (NCT03938792) evaluating HYMPAVZI™ (marstacimab) for adults and adolescents living with hemophilia A or B with inhibitors. The study met the primary endpoint and key secondary bleeding endpoints demonstrating the superiority of once-weekly subcutaneous HYMPAVZI in improving key bleeding outcomes compared to on-demand treatment in a patient population where less burdensome treatment approaches are needed.1,2,3,4
Inhibitors, or antibodies, which neutralize factor replacement therapies and render them ineffective, may develop in people living with hemophilia.5 Inhibitors can be diagnosed with a blood test.6 Of the more than 800,000 people in the world living with hemophilia A or hemophilia B, approximately 20% of people with hemophilia A and 3% of people with hemophilia B are unable to continue taking factor replacement therapies because they develop inhibitors to FVIII (Factor VIII) and FIX (Factor IX) and these therapies no longer prevent or stop bleeding episodes.6,7
"Patients with inhibitors tend to face frequent complications, and navigating the treatment landscape can introduce complexities and increase disease burden,"1,2,3,4,8 said Davide Matino, M.D., M.Sc., BASIS Principal Investigator, Associate Professor of Medicine, McMaster University. "The strong bleed reduction with HYMPAVZI compared to on-demand treatment in the Phase 3 BASIS study, coupled with its weekly administration method, offers exciting potential for these patients who are in critical need of treatment options."
The BASIS trial demonstrated that prophylactic treatment with HYMPAVZI resulted in a statistically significant and clinically relevant reduction in annualized bleeding rate (ABR) of treated bleeds in people living with severe hemophilia A or hemophilia B with inhibitors. Forty-eight people living with hemophilia were treated with HYMPAVZI during a 12-month period versus an on-demand intravenous regimen with bypassing agents, administered as part of usual care in the six-month lead-in period. HYMPAVZI was superior to on-demand treatment with a 93% reduction in ABR over 12 months (ABR 1.39 vs ABR on-demand 19.78; p < 0.0001). Superiority of HYMPAVZI was also demonstrated across all bleeding-related secondary endpoints-spontaneous bleeds, joint bleeds, target joint bleeds, and total bleeds.
HYMPAVZI was generally well-tolerated, consistent with the non-inhibitor cohort of the BASIS study and Phase 1/2 results. No deaths or thromboembolic events were reported.
"These encouraging results demonstrate HYMPAVZI's potential to help people living with hemophilia A or B with inhibitors, meeting an important need for patients with antibodies that neutralize most factor-based prophylactic options used to manage bleeding episodes," said Michael Vincent, M.D., Ph.D., Chief Inflammation & Immunology Officer, Pfizer. "HYMPAVZI represents Pfizer's latest contribution in more than 40 years of working to advance hemophilia care, as a generally well-tolerated treatment option that could offer bleed protection with a straightforward, once-weekly subcutaneous administration in a pre-filled pen for patients with inhibitors, if approved in this patient population."
Analyses of the full Phase 3 dataset from the inhibitor cohort of the BASIS study are ongoing, and additional data will be presented at upcoming medical meetings. Pfizer plans to discuss these data with regulatory authorities, with the goal of initiating regulatory filings for HYMPAVZI for the treatment of patients living with hemophilia with inhibitors.
Discovered by Pfizer scientists, HYMPAVZI has a mechanism of action that is differentiated from FVIII and FIX replacement treatments. Instead of replacing missing or insufficient clotting factors, HYMPAVZI is intentionally designed to target tissue factor pathway inhibitor (TFPI), one of the body's natural mechanisms that inhibits the initiation of blood clotting. By targeting the Kunitz 2 domain of TFPI, HYMPAVZI may help re-establish balance between bleeding and blood clot formation with the goal of offering a combination of bleed protection, good tolerability, and straightforward administration.
About the BASIS study
The pivotal BASIS study is a global Phase 3, open-label, multicenter study to evaluate the efficacy and safety of HYMPAVZI in adolescent and adult participants ages 12 to <75 years with severe hemophilia A (defined as FVIII <1%) or moderately severe to severe hemophilia B (defined as FIX activity ≤2%) with or without inhibitors.
This cohort included 48 people living with hemophilia with inhibitors who were treated with HYMPAVZI during a 12-month active treatment period (ATP) versus an on-demand intravenous regimen with bypassing agents, administered as part of usual care in a six-month observational period. During the ATP, participants received prophylaxis (a 300 mg subcutaneous loading dose of HYMPAVZI, followed by 150 mg subcutaneously once weekly) with potential for dose escalation to 300 mg once weekly. An additional three patients in the inhibitor cohort were on routine prophylactic treatment prior to the study and not included in the primary efficacy analysis.
