Setback lays bare Novo’s need in haemophilia

Novo Nordisk is in danger of being left behind in haemophilia, and new safety fears around its lead R&D project make this more likely. But could a setback prompt deal making?

Trial Results

Novo Nordisk’s strong position in the blood coagulation factors used to treat haemophilia is already being challenged by Roche’s hugely successful Hemlibra, while gene therapies are on the horizon. Now comes an internal setback: trials of the company’s biggest pipeline hope in this area, concizumab, have been paused because of safety concerns.

Three patients suffered non-fatal thrombotic events in phase III studies that started late last year, Novo said today. Unless a way forward can be found the Danish pharma giant will find itself without a growth story for this area of its business. Could this in turn prompt a rethink about the company's strategy of sticking to early-stage collaborations?

Last year, for example, Novo signed a deal with Bluebird Bio to investigate the use of in vivo genome editing, with the aim of making a haemophilia A therapy that could elicit a genetic change directly in patients. Work is extremely early: at the time Novo said any emerging project was unlikely to enter preclinical testing for at least three years (Novo goes early to leapfrog haemophilia gene therapies, October 10, 2019).

Gene therapies from the likes of Biomarin and Uniqure could reach the market later this year. So, if the concizumab delay proves fatal, Novo will start looking even further behind. As Vantage has previously suggested, making a move on one of the smaller gene therapy players could be smart (Why Novo Nordisk should buy Uniqure, October 11, 2019).

Concizumab is a tissue factor pathway inhibitor; this mechanism acts as the primary brake on the initiation of blood coagulation and is thought to modulate a variety of bleeding and clotting disorders. As such, concizumab is being trialled in haemophilia A and B, and could prove useful in patients with and without inhibitors – autoantibodies that render first-line coagulation factors unusable.

In 2019 Novo presented phase II data in which no thromboembolic events were seen. The two phase III programmes only started late last year, so it is alarming that the latest signal has been seen so quickly. The larger trials test a different dosing regime from the mid-stage programme and, perhaps importantly, patients are being given a larger loading dose than previously.

Concizumab was essentially Novo’s response to Roche’s Hemlibra, a bispecific MAb that is on the way to making $2bn in sales in 2020 – only its third full year on the market. Hemlira can only be used in haemophilia A, and given its entrenched position there was always a risk that concizumab would be consigned to the much smaller haemophilia B population.

Forecasts for concizumab suggest that analysts have yet to be convinced: EvaluatePharma's sellside consensus has only $126m pencilled in for 2024.

Still, Novo has long contended that a more convenient administration should also give concizumab an edge. Speaking to Vantage after presenting phase II data last year, the company’s head of biopharma, Ludovic Helfgott, said the project had “unsurpassed convenience”, describing a best-in-class device, smallest needles, very low volume and portability.

This only matters if concizumab can also compete on safety and efficacy, of course; a delay to the clinical programme looks like a best-case scenario here. But if Novo is serious about growing in haemophilia it might need to start considering a plan B.

Key concizumab trials 
Trial name/ID Setting  Status
Phase III
Explorer8 (NCT04082429) Haemophilia without inhibitors Paused: was due to complete late 2020
Explorer7 (NCT04083781) Haemophilia with inhibitors Paused: was due to complete late 2020
Phase II
Explorer5 (NCT03196297) Haemophilia A without inhibitors Paused: has reported results 
Explorer4 (NCT03196284) Haemophilia A and B with inhibitors Completed and reported 
Source: EvaluatePharma and company statements.

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