Novo Nordisk preps filings for sickle cell drug etavopivat

Novo Nordisk is planning to move ahead with regulatory filings for etavopivat, potentially a first-in-class therapy for sickle cell disease, based on positive results in a phase 3 trial.

In the HIBISCUS trial, oral PKR activator etavopivat showed a 27% reduction in the annualised rate of vaso-occlusive crisis (VOC) events – the excruciatingly painful attacks that occur in SCD patients when red blood cells become misshapen and block blood vessels – compared to placebo when added to standard treatment.

The time to first VOC was significantly prolonged with etavopivat, with a median time to first VOC of 38.4 weeks versus 20.9 weeks for placebo. The drug also achieved a significant increase in haemoglobin levels, with 48.7% of people on the drug achieving an increase of 1g/dL or more after 24 weeks, compared to 7.2% of the control group.

While the news flow at Novo Nordisk has been dominated of late by its GLP-1-based therapies for obesity and diabetes, HIBISCUS serves as a reminder of the company's rare disease pipeline, and analysts have already tipped potential $1 billion-plus peak sales for etavopivat based on the results if they lead to approval.

There is a race to market in the oral PKR category between Novo Nordisk and Agios, however, as the latter has said it intends to file its mitapivat candidate for accelerated approval based on feedback from the FDA – and despite mixed results in the phase 3 RISE UP trial.

Novo Nordisk seems to have the advantage with its VOC readout, as mitapivat wasn't able to show a significant improvement on that measure in its trial, and its filing plan is relying on haemoglobin data alone. In addition, etavopivat can be taken once daily, while mitapivat – which is already approved as Pyrukynd for pyruvate kinase (PK) deficiency – has twice-daily dosing.

Novo Nordisk said it plans to submit for the first regulatory approval of etavopivat in the second half of 2026.

"We are very excited that etavopivat has the potential to be a first and best-in-class therapy and transform the lives of people with sickle cell disease, who currently have limited therapeutic options," said the company's chief scientific officer, Martin Holst Lange.

Novo Nordisk acquired rights to etavopivat when it bought Forma Therapeutics for $1.1 billion in 2022, when the drug was in phase 2/3 testing and had already secured fast track and orphan status from the FDA. The drug is also in phase 2 development for beta-thalassaemia, another rare blood disorder.