ASH: Pfizer builds case for long-acting haemophilia drug

Pfizer’s once-weekly antibody injection for haemophilia A and B, marstacimab, could be on track for regulatory approvals based on solid results in a phase 3 trial reported over the weekend – if it can avoid the fate of Novartis’ similarly-acting drug.

The anti-tissue factor pathway inhibitor (TFPI) drug was effective at reducing annualised bleeding rates (ABR) in patients with haemophilia A and B in the BASIS trial, improving on standard clotting factor replacement therapy with a simple 150 mg injection given once a week.

The trial - which recruited people with severe haemophilia A and moderately severe to severe haemophilia B without inhibitors to Factor VIII (FVIII) or Factor IX (FIX) – showed a 35% reduction and 92% reduction in ABR, respectively, when compared to routine prophylaxis and on-demand treatment with standard therapies, which have to be administered multiple times a week.

At the American Society of Haematology (ASH) congress in San Diego, Pfizer reported new data from the study that showed that the benefits seen with the drug at 12 months were maintained over an additional 16 months of follow-up.

Pfizer has said the results give marstacimab a shot at becoming the first once-weekly subcutaneous treatment for people living with haemophilia B, as well as the first treatment administered as a flat dose – i.e. not determined by weight – for people living with either haemophilia A or B.

The company will be hoping to fare better with the FDA than Novartis’ TFPI antibody concizumab, which was turned down by the regulator earlier this year, reportedly on dosing, monitoring, and manufacturing grounds. It has been approved in Canada as Alhemo, but its once-daily dosing could impede widespread use.

If it reaches the market, marstacimab will compete in haemophilia A with Roche’s roaring success Hemlibra (emicizumab), which has less frequent dosing and is approved for patients with and without inhibitors, as well as Sanofi’s long-acting FVIII replacement therapy Altuviiio (efanesoctocog alfa), which also offers once-weekly dosing.

The presence of established players in the market means that the greatest potential for Pfizer’s drug probably lies in haemophilia B, where there is currently no once-weekly subcutaneous option.

The BASIS trial is still ongoing and also includes an inhibitor-positive cohort that will read out next year. In the meantime, Pfizer is also developing gene therapies for haemophilia A and B - respectively, giroctocogene fitelparvovec and fidanacogene elaparvovec – for which new data will also be presented later at ASH.