Pfizer posts another haemophilia hit

The group is taking marstacimab to the regulators, but Novo’s MAb looks like a bad omen.

The success of Pfizer’s haemophilia project marstacimab in its pivotal trial today is impressive, following on from a hit with one of its gene therapies at the end of last year. The data could position the antibody as the first weekly subcutaneous product for haemophilia B patients, whereas in haemophilia A it could compete with Roche’s Hemlibra and Sanofi’s Altuviiio.

But Novo Nordisk’s similarly acting concizumab, which was rejected by the FDA at the start of this month, remains a cautionary tale. If push comes to shove Pfizer has two other chances with a couple of late-stage gene therapies – though it will hope that marstacimab defies concizumab’s precedent.

Marstacimab's Basis trial enrolled patients with severe haemophilia A or moderate to severe haemophilia B, with or without inhibitors. Subjects were given a 300mg loading dose followed by 150mg once a week for a year. The annualised bleeding rate (ABR) seen in that time was compared with that in an earlier six-month period where patients were given intravenous factor VIII or IX either prophylactically or on demand, administered as part of usual care.

Today’s data come from patients without inhibitors; the inhibitor cohort of Basis is still enrolling, and should read out in late 2024.

Among the patients given on-demand factor replacement in the lead-in period, marstacimab reduced bleeds by 92%, demonstrating superiority (p< 0.0001) over the control arm. The results also showed superiority (p=0.0376) with marstacimab versus prophylactic factor use, with a 35% reduction in ABR.

Pfizer did not break the results down by haemophilia type. In haemophilia A, the data do not look like a threat to Altuviiio and Hemlibra, according to SVB analysts. Those products' US labels show 77% and 68% ABR reductions in the prophylaxis arms of their pivotal studies, respectively. In the pivotal study of Sanofi’s Altuviiio, the on-demand arm showed a 98% reduction in bleeds.

On safety, Pfizer said its antibody was generally well-tolerated, and crucially there were no thromboembolic events. This is relevant because Novo's concizumab – like marstacimab an anti-tissue factor pathway inhibitor – was previously paused because of blood clot concerns

Novo admitted on its first-quarter earnings call that concizumab had been knocked back in the US as a therapy for haemophilia A and B patients with inhibitors. The FDA requested further data on monitoring and dosing, as well as on manufacturing. 

Pfizer will need marstacimab to maintain its apparently benign safety profile, but in the meantime it hopes to file the antibody in the coming months.

Gene therapies

The company also has two other late-stage haemophilia projects. 

These are both gene therapies. Fidanacogene elaparvovec posted a hit late last year, and looks competitive with Uniqure/CSL’s rival haemophilia B gene therapy Hemgenix. And pivotal data on the Sangamo-originated giroctocogene fitelparvovec in haemophilia A could emerge next year.

According to forecasts compiled by Evaluate Pharma the sellside sees fidanacogene elaparvovec as the biggest seller of these three in five years’ time. 

Pfizer's phase 3 haemophilia programmes
Project Mechanism Status 2028e forecast sales ($m)
Marstacimab (PF-06741086) Tissue factor pathway inhibitor antibody Basis, in haemophilia A and B pts w/o inhibitors, hit May 2023; data on pts w inhibitors expected 2024 181
Fidanacogene elaparvovec
Gene therapy delivering factor IX Benegene-2, in men w moderate to severe haemophilia B, hit Dec 2022 385
Giroctocogene fitelparvovec
Gene therapy delivering factor VIII Affine, in pts w moderate to severe haemophilia A, halted in Nov 2021 and restarted Sep 2022; could report 2024 272
Source: Evaluate Pharma, & company releases. 

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