Pfizer has unveiled phase 3 results that could help the company’s hemophilia drug Hympavzi level the playing field in its competition with Sanofi’s Qfitlia and Novo Nordisk’s Alhemo.
After an FDA approval about a year ago for the treatment of hemophilia in patients without inhibitors, Pfizer now has detailed data showing prophylactic Hympavzi can outperform traditional therapies at controlling bleeding in patients with inhibitors.
Among 48 patients with hemophilia A or B who transitioned from on-demand therapy with bypassing agents, Hympavzi significantly reduced average annual bleeding rates (ABRs) for treated bleeds from 19.8 to 1.4, according to results from the inhibitor cohort of the phase 3 Basis trial presented at the American Society of Hematology (ASH) 2025 annual meeting.
During the 12-month active treatment phase, the tissue factor pathway inhibitor (TFPI) was associated with an ABR of 1.1 for treated joint bleeds, versus 15.2 recorded for traditional therapies during a six-month observational phase before the patients transitioned to Hympavzi. The ABRs for treated spontaneous bleeds were 0.9 versus 15.3, respectively.
Hympavzi showed generally consistent results across 40 hemophilia A patients and eight individuals with hemophilia B, according to an ASH presentation. The drug’s treatment effect appeared a little weaker in the hemophilia B subgroup, though, as one patient who had an ABR of 16.6 during the observational phase only achieved a rate of 14.9 after Hympavzi treatment.
“It’s more anecdotal evidence than anything else. It’s difficult to draw specific conclusions for a single patient,” Davide Matino, M.D., from McMaster University, principal investigator of the Basis trial, said in an interview with Fierce Pharma.
The hemophilia market has become increasingly crowded by the likes of Roche’s hemophilia A blockbuster Hemlibra and up-and-coming gene therapies. But, for Hympavzi, the more comparable competitors are Novo Nordisk’s rival TFPI Alhemo and Sanofi’s Qfitlia, both of which boast broad FDA nods covering patients 12 years and older with hemophilia A or B regardless of their inhibitor status. In hemophilia, inhibitors are antibodies that counter infused clotting factor replacement therapies.
Besides a broader label—which Pfizer is trying to match—Sanofi’s Qfitlia also holds a dosing frequency advantage. The antithrombin-directed RNA interference therapy, discovered by Alnylam, is given once every two months, whereas Hympavzi is administered weekly. Novo’s Alhemo is dosed daily.
Adopting the imperfect method of cross-trial comparisons, Hympavzi’s data appear to be slightly better than Qfitlia’s in the inhibitor patient population.
In hemophilia patients with inhibitors, Qfitlia showed an ability to lower ABRs from on-demand bypassing agents’ 19.1 to 5.1, according to the Sanofi drug’s label. The ABRs were 14.4 and 4, respectively, for the two agents in treated joint bleeds, and 17.1 and 3.1, respectively, for treated spontaneous bleeds.
However, Qfitlia carries a boxed warning detailing the risk of thrombotic events and gallbladder disease associated with the treatment. The drug was originally tested at an 80-mg monthly dose in the three clinical trials supporting its FDA approval. But that high dose was not approved because of those two safety signals and liver toxicity.
The Sanofi drug is now cleared in single-dose presentations of 50 mg and 20 mg, with 50 mg once every two months being its starting dose. Qfitlia’s label also calls for monitoring of antithrombin activity within a specified range through FDA-approved assays and potential dose modifications to reduce the risk of thrombosis.
By comparison, Hympavzi’s current non-inhibitor label doesn’t have a boxed warning or a patient monitoring requirement. In the “Warnings and Precautions” section, the med’s label includes risks related to thromboembolic events, hypersensitivity and embryo-fetal toxicity.
In the inhibitor patients enrolled in the Basis trial, no deaths or thrombotic events were reported, according to the ASH presentation. One patient experienced a serious treatment-related adverse event of skin rash at grade 3, which led to study discontinuation. Across the entire Basis trial, one thromboembolic event was reported in the non-inhibitors group.
Novo’s Alhemo also doesn’t have a boxed warning. But, unlike Hympavzi’s typically flat dose for all patients, Alhemo requires individualized adjustments of maintenance doses four weeks after initiation of treatment based on a blood test of drug concentration. Additional measurements of Alhemo plasma concentrations should also be taken at routine clinical follow-ups, according to the drug’s label.
Hympavzi is currently the only one of the three agents that requires no measurements to identify the right dose, Matino noted. The drug can be given at a higher dose if a patient experiences two or more bleedings in six months.
The inhibitors cohort in the Basis trial also included three patients who transitioned from traditional prophylactic therapy rather than on-demand treatment. The ASH presentation does not include results from those individuals.
Previously, in the non-inhibitor population of the Basis study, patients did better on Hympavzi with a recorded ABR of 5.1, compared with 7.9 before switching from routine factor-based prophylactic therapy. Unlike non-inhibitor patients, factor-based prophylactic treatments typically do not work well in patients with inhibitors, Matino said.
Hympavzi represents Pfizer’s focus in hemophilia after the New York pharma scrapped a near-market hemophilia A gene therapy project sourced from Sangamo Therapeutics and then discontinued its Roche-partnered hemophilia B gene therapy Beqvez, citing limited interest.