Novo Nordisk's phase 3 data for hemophilia hopeful fail to shake off Pfizer's shadow

Novo Nordisk insists its rival to Roche's Hemlibra will make a “good offering” for hemophilia patients even though mixed phase 3 data suggest that Pfizer’s own candidate could have an edge in the race to market.

The Danish drugmaker is developing concizumab, an anti-tissue factor pathway inhibitor (TFPI) antibody, to treat people with both hemophilia A and hemophilia B. Having already posted impressive phase 3 data last year from the explorer7 trial of patients with inhibitors—an immune system response to the clotting factors—the Big Pharma used the International Society on Thrombosis and Haemostasis conference in Montreal to release data from the explorer8 trial in 148 patients without these inhibitors.

The top-level numbers look good. The therapy induced an 86% reduction in spontaneous and traumatic bleeds in hemophilia A patients and a 79% reduction among trial participants with hemophilia B.

However, the figures looked slightly less impressive when compared to Pfizer’s own anti-TFPI drug marstacimab, which posted a 92% reduction in bleeds in a phase 3 trial of patients without inhibitors less than a month ago.

In a media briefing, Henrik Jarlov, Novo Nordisk’s vice president for medical affairs, rare disease, insisted that there’s no head-to-head data available yet to truly compare the Big Pharmas’ rival options.

“We’ve only seen the high-level data from marstacimab, so I think we would like to wait until we’ve seen the full data set before the scientific community makes up their mind on a treatment option,” Jarlov said.

Another area where today’s concizumab data came up short was in demonstrating noninferiority to previous hemophilia prophylaxis treatment that patients receive. This was most notable among hemophilia A patients, who had a mean annualized bleeding rate (ABR) of 5.1 for those who received concizumab compared to just 3.7 for those on another prophylaxis treatment. A similar problem was reflected in hemophilia B patients, with an ABR of 5.4 for the concizumab cohort compared to 3.1 for those on previous prophylaxis.

Study investigator Anthony Chan blamed this discrepancy on three patients across the hemophilia A and B cohorts who showed “substantially” increased levels of bleeding. He pointed to the estimated median ABR as a better measure as it’s “less prone to outliers.” Indeed, on this measure, bleed rates were level among hemophilia A patients and even slightly lower for hemophilia B patients who received concizumab.

Still, it’s another aspect where Pfizer now appears to have the upper hand, with marstacimab showing superiority to prophylaxis in its own phase 3 trial.

Meanwhile, Novo Nordisk said the safety and tolerability profile of concizumab was within the expected range. Overall, there were 104 adverse events, including 14 that were deemed serious. One of these was a fatality, which was related to intra-abdominal bleeding, Chan said on the call.

There have been no more thromboembolic events since the trial was paused in 2020 while two such cases were investigated, the company noted.

Despite what looks set to be a tight race against Pfizer, both Chan and Jarlov were confident that conziumab had a role to play in the hemophilia landscape. With Novo Nordisk hoping that patients will be able to administer concizumab at home with a pen injector-style device, both speakers pointed to the therapy’s subcutaneous delivery as a benefit.

“One of the facts that is worth keeping in mind with concizumab is that the device and the burden for patients in terms of administering the treatment is also something that we’ve seen quite good data in the explorer8 study,” Jarlov said. “We did not share the full data in terms of the reduction of [disease] burden for patients with hemophilia, but there’s also a clear impact there.”

“I believe with what we’ve seen [of] concizumab with the subcutaneous option and the data that we have, I’m quite confident that that will be a good offering for many patients with hemophilia A [and] B, with or without inhibitors,” he added.

Whether regulators agree remains another matter. While Canadian authorities have already given the green light, the FDA requested additional information on dosing from Novo Nordisk last month before it will make a call.