Dive Brief:
- An experimental hemophilia drug developed by Pfizer significantly reduced bleeding frequency compared to on-demand or preventive clotting factor proteins, the drugmaker said Tuesday. Called marstacimab, the drug was not associated with the kind of dangerous blood clotting that has delayed or sidelined similarly acting drugs from Novo Nordisk and Bayer.
- If approved, marstacimab would compete with established medicines like Roche’s Hemlibra as well as newer treatments like CSL Behring’s gene therapy Hemgenix and Sanofi’s long-acting drug Altuviiio. These therapies offer options for patients beyond regular infusions of engineered clotting factor proteins.
- Marstacimab requires a weekly subcutaneous shot, while Hemlibra can be administered subcutaneously as infrequently as once every four weeks after an initial dosing phase. Gene therapies like Hemgenix, or another from BioMarin Pharmaceutical that’s now under review, are intended to be a one-and-done treatment, although their long-term durability has not been proven.
Dive Insight:
Hemophilia treatment has until now involved increasing the body’s supply of clotting factor proteins, which are low in patients because of a genetic mutation. Marstacimab takes a different approach by shutting down a protein that impedes blood clotting.
This approach has been tried by other drugmakers, but those efforts have been hampered by safety risks in clinical testing. In response, regulators have slowed down development.
The Food and Drug Administration rejected Novo Nordisk’s concizumab earlier this year, seeking more information about dosing and monitoring of patients, while Bayer terminated a Phase 2 dosing trial of a drug called befovacimab because of dangerous clotting.
Marstacimab is intended to treat both hemophilia A and B, which result from different mutations and cause reductions in different clotting proteins. Most other treatments can only be used for one type of hemophilia.
Among the 116 patients treated with marstacimab for 12 months or more in a Phase 3 trial, annualized bleeding rates were 92% lower in patients who previously used clotting factor proteins “on demand” to stop a bleed, Pfizer said. In patients who were treated preventively, marstacimab was statistically superior, too, reducing bleeding incidents by 35%.
There were no dangerous blood clotting incidents reported in the study, according to Pfizer. The company said it has begun discussions with the FDA and other regulators and hopes to file an approval application in the coming months.
While the trial had no clotting incidents, treatment with marstacimab has resulted in biomarker elevations that suggest it could still be a risk, Evercore ISI analyst Umer Raffat wrote in a Tuesday note to clients.
“Safety profile in ongoing studies and future exposure remains key,” he added.
SVB Securities analyst David Risinger wrote that, in hemophilia A, marstacimab’s data on bleeding frequency didn’t look as good as that for Hemlibra or Sanofi’s new drug Altuviiio. On its side is a “flat” dosing regimen, as opposed to the dosing regimen of Hemlibra and Altuviiio, which are based on patients’ weight.
“It’s unclear how much of a commercial advantage this will be,” Risinger wrote.