Marstacimab seen to lower bleed rates in hemophilia in Phase 3 trial
Weekly treatment found effective for patients without inhibitors
Weekly treatment with the experimental therapy marstacimab (PF-06741086) was found to significantly reduce bleed rates for adult and adolescent hemophilia A and B patients without inhibitors relative to standard therapies.
In so doing, it met the main goal of the pivotal Phase 3 BASIS clinical trial, designed to evaluate the treatment’s effectiveness in preventing bleeds in these two main types of hemophilia.
Pfizer, the therapy’s developer, plans to discuss these Phase 3 data with regulatory authorities in the coming months and begin the process of seeking marstacimab’s regulatory approval.
“These encouraging results from the BASIS trial demonstrate marstacimab’s potential as a promising subcutaneous [under-the-skin] treatment option that could offer improvement over the current standard of care for many living with hemophilia,” Davide Matino, MD, assistant professor of medicine at McMaster University, in Canada, said in a company press release.
“If approved, marstacimab may both prevent bleeds and reduce the treatment burden that many people living with hemophilia A or B without inhibitors face today,” Matino said.
Marstacimab has potential to reduce treatment burden for patients
While full analyses for that part of the trial are still ongoing, BASIS (NCT03938792) is meanwhile completing enrollment of a group of patients who do have inhibitors. These are a type of neutralizing antibody against blood clotting proteins that can make standard replacement therapies less effective.
The Phase 3 BASIS KIDS trial (NCT05611801) is concurrently investigating the safety and efficacy of marstacimab in pediatric patients. That trial is now recruiting an estimated 100 children younger than age 18 with severe hemophilia A or moderately severe to severe hemophilia B with or without inhibitors. Enrollment is ongoing at sites in India, Korea, and South Africa, with additional sites expected to open in Canada, Japan, Taiwan, and Turkey.
Hemophilia A and B are caused by genetic mutations that lead to a lack of proteins needed for blood clotting. In hemophilia A, patients need factor VIII (FVIII), while factor IX, known as FIX, is lacking in people with hemophilia B.
The mainstay treatment for hemophilia is replacement therapy, which aims to provide patients with a working version of the protein they are missing. These treatments typically involve frequent into-the-vein (intravenous) infusions that, while effective, can place a burden on patients.
Moreover, some individuals with hemophilia develop neutralizing antibodies, or inhibitors, against the provided clotting proteins, lowering the treatment’s efficacy.
“Despite significant treatment advances in recent years, many people living with hemophilia unfortunately continue to experience bleeding episodes and are required to manage their disease with frequent intravenous infusions,” said Chris Boshoff, MD, PhD, chief development officer of oncology and rare disease at Pfizer’s global product development division.
Marstacimab is an antibody-based therapy that targets TFPI, or tissue factor pathway inhibitor, one of the body’s natural mechanisms to suppress blood clotting. By blocking TFPI, Pfizer believes marstacimab will help prevent bleeds for people with severe hemophilia A or moderate to severe hemophilia B, regardless of their inhibitor status.
The experimental therapy is delivered as a weekly, under-the-skin (subcutaneous) injection — with doses needed less frequently compared with other medications.
Pfizer believes marstacimab offers significant potential to meet the needs of hemophilia patients, including “preventing excessive or potentially life-threatening bleeds, while at the same time reducing the burden of treatment with once-weekly, subcutaneous administration,” according to Boshoff.
Treatment with marstacimab would be first given once-weekly
The first part of the BASIS trial enrolled 116 patients without inhibitors, ages 12-74, to evaluate the treatment’s safety and efficacy.
During a six month lead-in period, all participants received standard-of-care preventive or on-demand FVIII or FIX replacement therapy. Participants were then given a 300 mg loading dose of marstacimab, followed by weekly 150 mg doses of the therapy for a year. Maintenance weekly doses could be increased to 300 mg under certain conditions.
Results now show that marstacimab led to a significant and clinically relevant 92% reduction in annualized bleed rates relative to on-demand replacement therapy during the lead-in period.
Likewise, the experimental treatment was associated with a significant 35% reduction in bleed rates compared with preventive replacement therapy.
Safety findings were similar to those of previous studies, with marstacimab being generally well-tolerated. No deaths or abnormal blood clotting incidents were reported.
These results support the potential for marstacimab to become the first once-weekly non-factor treatment for people with hemophilia B and a treatment option that helps address the diverse needs of patients with hemophilia A or B without inhibitors.
The findings to date from BASIS overall were consistent with those from a previous Phase 1b/2 clinical study (NCT02974855). In that trial, treatment was well-tolerated and lowered bleed rates among men with severe hemophilia with or without inhibitors.
“These results support the potential for marstacimab to become the first once-weekly non-factor treatment for people with hemophilia B and a treatment option that helps address the diverse needs of patients with hemophilia A or B without inhibitors,” Boshoff said.
The enrollment of an additional group of patients with inhibitors is intended to evaluate whether marstacimab is similarly effective for that population. Results from that part of the study are expected at the end of 2024.
All patients who complete BASIS can opt-in to an open label extension study (NCT05145127), in which all will receive the therapy for up to seven years.