- Etavopivat (400 mg once daily) is an oral pyruvate kinase‑R (PKR) activator that lowers 2,3‑DPG and raises ATP to increase Hb‑oxygen affinity and improve RBC survival.
- HIBISCUS phase‑3 (n=385, >=12 yrs, 52 weeks) showed etavopivat reduced annualised VOCs by 27% and delayed median time to first VOC to 38.4 vs 20.9 weeks (~4 months).
- 48.7% on etavopivat achieved >1 g/dL Hb increase at week 24 vs 7.2% placebo (adjusted difference 41.2%); Novo Nordisk plans first regulatory submission in H2 2026 and acquired etavopivat via the 2022 Forma Therapeutics deal.
Trial and outcomes
HIBISCUS was a randomized, double‑blind 52‑week phase‑3 trial (n=385, ≥12 years) of etavopivat 400 mg once daily versus placebo on top of standard of care; etavopivat reduced the annualised rate of vaso‑occlusive crises by 27% and extended median time to first VOC to 38.4 weeks versus 20.9 weeks for placebo. At week 24, 48.7% of treated participants achieved a >1 g/dL haemoglobin increase versus 7.2% with placebo (adjusted rate difference 41.2%); an exploratory analysis showed reduced transfusion risk.
Safety
Topline safety was consistent with prior etavopivat trials and the drug appeared to be well tolerated in the study population.
Mechanism of action
Etavopivat is an oral, once‑daily allosteric activator of red blood cell pyruvate kinase (PKR); PKR activation lowers 2,3‑DPG and increases ATP, improving Hb–oxygen affinity, reducing sickle haemoglobin polymerisation and supporting RBC membrane integrity and survival.
Development plan
Novo Nordisk plans the first regulatory submission for etavopivat in the second half of 2026; etavopivat was acquired in 2022 as part of the Forma Therapeutics deal. The HIBISCUS programme also includes HIBISCUS2 (a 52‑week phase‑3b trial) and FLORAL, an open‑label extension to collect long‑term safety data, with detailed phase‑3 results slated for presentation at a scientific conference in 2026.
