Takeaways:
- The phase 3 BASIS trial presented at ASH demonstrated a significant reduction in annualized bleeding rate (ABR) with marstacimab in severe hemophilia A and B patients.
- Marstacimab showed a 35.2% mean reduction in ABR compared to routine prophylaxis (RP) and a 91.6% reduction compared to on-demand (OD) treatment over 12 months.
- Consistent ABR reductions were observed across hemophilia A and B groups for OD and across hemophilia A and B and age groups for RP.
- Patients could continue marstacimab in a long-term extension (LTE) study, maintaining ABR reductions for up to an additional 16 months.
- Marstacimab was well-tolerated with common adverse events including hemorrhage, hepatic disorder, COVID-19, hypersensitivity, hypertension, and injection site reaction. One serious adverse event (peripheral swelling) was reported, and one patient discontinued due to a non-treatment-related event.
A statistically significant and clinically meaningful effect on the annualized bleeding rate (ABR) in patients with severe hemophilia A and moderately severe to severe hemophilia B without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) was observed for those treated with marstacimab (Pfizer), according to results presented at the American Society of Hematology (ASH) Annual Meeting and Exposition.
Results presented at the meeting, held in December 2023 from San Diego, California, were from the phase 3 BASIS trial (NCT03938792), evaluating ABR with marstacimab treatment in 116 adolescent and adult participants aged 12 to <75 years living with hemophilia.
According to Pfizer, the open-label, multicenter study evaluated ABR through 12 months of treatment with investigational, novel marstacimab, a subcutaneous therapy. Approximately 15% of participants are aged 12 to 18 years.
Marstacimab treated patients were compared to a routine prophylaxis (RP) and on-demand (OD) intravenous regimen with FVIII or FIX that was administered as part of usual care in a 6-month observation period.
Non-weight-based dosing was used for marstacimab-treated patients once weekly. Dosing consisted of a subcutaneous 300 mg loading dose followed by 150 mg dose each week.
Marstacimab treatment demonstrated a 35.2% mean reduction in ABR across 12 months (mean of 7.85 [5.09-10.61] to 5.08 [3.40-6.77]) compared to RP (95% CI, 5.6-55.6 [P = 0.0376]). Compared to OD, marstacimab reduced ABR by 91.6% (95% CI, 88.1-94.1 [P < 0.0001]) over 12 months (mean of 38.00 [31.03-46.54] to 3.18 [2.09-4.85]).
Mean ABR reductions with marstacimab treatment were consistent across hemophilia A and B groups for OD, and “were generally consistent” across hemophilia A and B and age groups for RP, with all point estimates for a difference less than 2.5 according to Pfizer.
Patients had an option to continue marstacimab treatment after the 12 month active treatment period as part of a long-term extension (LTE) study. Consistent reduction in ABR compared to OD, along with further numerical reduction compared to RP, were observed for up to an additional 16 months of follow up in the LTE (n = 87).
Across all bleeding-related secondary endpoints in the OD group—joint bleeds, spontaneous bleeds, target joint bleeds, and total bleeds—superiority (P < 0.0001) of marstacimab was observed.
Marstacimab demonstrated non-inferiority to the secondary endpoints in the RP group.
“Recognizing the uncertainty that living with hemophilia can present for patients, the results from the BASIS trial are particularly encouraging as reductions in ABR were seen in the 12-month treatment period and then retained in long-term follow-up,” said Davide Matino, MD, MSc, assistant professor of Medicine, McMaster University, in the press release.
“Based on these results, marstacimab has shown the potential to address the diverse needs of appropriate patients with hemophilia A or B without inhibitors with weekly subcutaneous administration in a flat dose that is not weight-based, and with low monitoring requirements,” added Matino.
Health-related quality of life parameters demonstrated, “non-significant improvements vs OD therapy and non-inferiority [vs] RP therapy,” Pfizer stated.
The most commonly reported adverse events among patients treated with marstacimab in the phase 3 trial and the LTE (≥5% of patients) were hemorrhage, hepatic disorder, COVID-19, hypersensitivity, hypertension, and injection site reaction.
There was 1 serious adverse event related to treatment (peripheral swelling). One patient discontinued the trial because of a non-treatment-related serious adverse event.
Overall, marstacimab was well-tolerated according to Pfizer, and no deaths or thromboembolic events were reported.
Reference:
Marstacimab phase 3 data presented at ASH 2023 demonstrate significant bleed reduction in hemophilia A and B. Pfizer. Press release. December 9, 2023. Accessed January 8, 2024. https://www.pfizer.com/news/press-release/press-release-detail/marstacimab-phase-3-data-presented-ash-2023-demonstrate
