Undeterred by last year’s rejection and the recent approval of a close rival from Pfizer, Novo Nordisk has pushed its once-daily hemophilia injection across the regulatory finish line days before we hit 2025.
Late last week, Novo revealed that the FDA approved its tissue factor pathway inhibitor (TFPI) antagonist concizumab as a once-a-day treatment to prevent or curb the frequency of bleeding episodes in patients ages 12 and older who have hemophilia A or B with inhibitors.
The prophylactic, which comes in prefilled, premixed pens for subcutaneous injection, will be marketed under the commercial title Alhemo, Novo said in a release.
As it stands, many treatments for hemophilia A or B with inhibitors are dosed via intravenous infusions, with Novo asserting that Alhemo is the first subcutaneous injection of its kind in this particular patient population.
Hemophilia with inhibitors is a complication of the genetic bleeding disorder that can prevent factor replacement treatments—a well-established class of therapeutics for the condition—from working properly.
About 30% of patients living with severe hemophilia A and 5% to 10% of those with severe hemophilia B develop inhibitors, which often complicates their treatment, according to Novo Nordisk. The company estimates that about 800,000 people live with hemophilia worldwide, with some 32,000 patients located in the U.S.
Patients with hemophilia B with inhibitors have been in an especially tricky bind, with few prophylactic treatment options to prevent bleeding for their specific condition on offer, the company added.
Alhemo, for its part, is designed to block a protein called TFPI that stops blood from clotting. By blocking this protein, Alhemo is though to boost production of thrombin, another protein that helps clot blood and prevent bleeding, when a patient’s other clotting factors or missing or deficient in the presence of inhibitors, Novo explained.
The FDA based its approval on results from Novo’s late-stage explorer7 study, which found that Alhemo helped reduce patients’ annual bleeding rate (ABR) by 86% versus participants who received no prophylaxis.
Digging deeper into the data, the estimated average ABR for patients on Novo’s drug was 1.7 versus 11.8 for patients with no prophylaxis, while the respective median ABR was zero for treated spontaneous and traumatic bleeds versus 9.8 ABR, Novo said.
Meanwhile, on a supportive secondary efficacy endpoint, 64% of patients on Alhemo experienced zero treated spontaneous and traumatic bleeds during the first 24 weeks of treatment compared to 11% of patients who didn’t receive prophylaxis over that same period.
"The approval of Alhemo signifies a remarkable achievement in prophylactic hemophilia treatment for individuals with inhibitors aged 12 years and older who, in some cases, currently have few options," Anna Windle, Ph.D., Novo’s senior vice president of clinical development, said in a statement. “As the first treatment of its kind for this population, Alhemorepresents a significant step in helping to address the unmet needs of patients with hemophilia with inhibitors.”
While Novo has at long last won regulatory recognition for concizumab in the U.S., the path to approval has been anything but easy.
Back in 2020, the FDA forced Novo to halt trials of the drug over reports of blood clots in three patients. Novo ultimately resumed its studies five months later and told Fierce Biotech in 2022 that the issues were in the rearview mirror.
Then, last May, Novo execs revealed on an earnings call that the therapy had received a complete response letter from the FDA, with the agency requesting additional information on both dosing and the company’s manufacturing process for concizumab.
All told, the drug has had a much smoother run outside the U.S. up to this point, snagging green lights in countries like Australia, Japan and Switzerland as well as the EU.
And, while Novo did manage to clear the FDA’s desk with Alhemo before 2024 is out, the Danish drugmaker wasn’t fast enough to beat Pfizer to the hemophilia finish line.
Back in October, Pfizer won the FDA’s favor on its own TFPI drug Hympavzi, which is specifically approved in hemophilia A or B patients who have not developed antibodies to previous inhibitor treatments.
Given that the drugs target two different hemophilia patient populations—those with inhibitors and those without—direct competition between Novo and Pfizer’s offerings is unlikely.
Elsewhere on the hemophilia front, Novo is looking to challenge Roche’s bleeding disorder stalwart Hemlibra, which generated nearly $4.8 billion in sales last year.
To take on Roche’s blockbuster, Novo is advancing Mim8, a bispecific antibody designed to bridge Factor IXa and X to replace missing Factor VIII in an approach that mirror’s Hemlibra’s own.
In May, Novo said its candidate had met the co-primary endpoints of its phase 3 trial, linking both once-weekly and once-monthly Mim8 to statistically significant reductions in treated bleeding episodes.