Novo Nordisk's Hemlibra rival faces another approval setback as FDA raises dosing, manufacturing questions

Three years after the FDA forced Novo Nordisk to pause a trial of its potential Hemlibra rival over reports of blood clots, the U.S. regulator has placed further barriers in front of the drug—even as it secures approval in other territories.

In a first-quarter earnings call this morning, Martin Holst Lange, M.D., Ph.D., Novo Nordisk’s executive vice president of development, revealed that on April 24 the Big Pharma received a complete response letter from the FDA regarding the therapy, an anti-tissue factor pathway inhibitor antibody called concizumab.

“In the letter, the FDA requested additional information related to the monitoring and dosing of patients to ensure that concizumab is administered as intended,” Lange explained. “Further information on the manufacturing process was also requested.”

“We will work now closely with the FDA to provide the requested data,” he added.

The latest holdup will bring back memories of 2020, when Novo Nordisk was forced to halt trials of concizumab over reports of blood clots in three patients. The studies resumed five months later, and, in a 2022 interview, executives insisted to Fierce Biotech that those issues were now in the rearview mirror.

“We worked with the FDA and the European agencies to evaluate the data from these three cases,” Novo Nordisk's chief medical officer for rare disease, Stephanie Seremetis, M.D., said at the time. “We described a mitigation strategy that has clearly been effective and since we restarted the trials we had no additional thrombotic events.”

The Big Pharma confirmed to Fierce this morning that no new safety issues have been identified related to the drug, while the therapy's “safety/efficacy profile is consistent with what we have observed in clinical trials to date.” Novo will “work closely with the FDA as plans for resubmission continue,” the spokesperson added.

The available data were presumably enough to convince Canadian regulators, who gave the green light to concizumab, marketed as Alhemo, last month for patients with hemophilia B who have FIX inhibitors and require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

Administered as a daily dose via what the company describes as a “patient-friendly pen,” concizumab’s big selling point over Roche’s hemophilia mainstay Hemlibra is that it can be taken by patients with hemophilia B, for which there are currently limited treatment options. The therapy already proved its worth last year, when the explorer7 study showed an 86% reduction in treated spontaneous and traumatic bleeds.

With a significant approval already in the bag, clinical data that exceeded the company’s expectations and confidence that its blood clot mitigation strategy is up to scratch, Novo Nordisk will be hoping that it can quickly overcome the FDA’s final regulatory approval and achieve its long sought-after U.S. approval.