Novo Nordisk’s Sickle Cell Treatment Shows 27% Reduction in Vaso-Occlusive Crises, FDA Approval Expected Later in 2026

Novo Nordisk announced that its sickle cell treatment, etavopivat, reduced annualized vaso-occlusive crises by 27% in a Phase 3 trial involving 385 patients aged 12 and older. According to company officials, the once-daily oral drug works by activating pyruvate kinase-R to prevent red blood cell sickling and is expected to seek FDA approval in the second half of 2026.

This nearly four-month delay was observed on top of the standard of care, highlighting the drug’s potential to reduce the frequency and severity of painful VOC events in people with sickle cell disease (SCD).

The Phase 3 HIBISCUS trial showed that etavopivat significantly delayed the time to first vaso-occlusive crisis (VOC), with patients experiencing their first crisis at 38.4 weeks compared to 20.9 weeks for those receiving placebo, according to Novo Nordisk officials.

The trial enrolled 385 participants aged 12 years and older who were treated over a 52-week period with a once-daily 400-mg oral dose of etavopivat, a pyruvate kinase-R (PKR) activator. The drug’s mechanism works by preventing the sickling of red blood cells, which is the underlying cause of vaso-occlusive crises, according to company statements and published trial data. Both co-primary endpoints of the study were met, with etavopivat demonstrating a 27% reduction in annualized VOC rate and a superior hemoglobin response compared to placebo.

Specifically, 48.7% of patients treated with etavopivat achieved a hemoglobin increase greater than 1 gram per deciliter at 24 weeks, compared to 7.2% in the placebo group, representing a 41.2% adjusted rate difference, Novo Nordisk reported. This hemoglobin improvement is a key measure of treatment efficacy and supports the drug’s potential to improve oxygen delivery and reduce the complications associated with sickle cell disease.

Clinical safety data from the HIBISCUS trial indicated that etavopivat was well tolerated, with a safety profile consistent with previous studies of the drug. No major safety concerns emerged that would impede the regulatory approval process, according to company officials. The inclusion of adolescents aged 12 years and older alongside adults provided a broad assessment of the drug’s safety and efficacy across a wide age range.

Novo Nordisk acquired etavopivat in September 2022 as part of its $1.1 billion purchase of Forma Therapeutics, the original developer of the drug candidate. The acquisition added etavopivat to Novo Nordisk’s pipeline as a first-in-class oral treatment for sickle cell disease, designed to improve patient convenience and compliance with a once-daily tablet formulation. Company leadership has described etavopivat as a potential “first and best-in-class therapy” for SCD.

The company plans to submit regulatory filings for etavopivat in the third or fourth quarter of 2026, with FDA approval expected in the second half of that year, Novo Nordisk said. Detailed results from the HIBISCUS trial are scheduled to be presented at a scientific conference in 2026.

Analysts from Truist Securities noted that the trial results create “separation amongst PK class candidates,” although no direct head-to-head comparisons have been conducted between etavopivat and competing drugs such as mitapivat. Mitapivat, another PKR activator, showed a 40.6% hemoglobin response rate in its Phase 3 data released in November 2025. Cross-trial comparisons remain inconclusive, according to market analysts, but the data put pressure on other drugmakers developing therapies for sickle cell disease.

Sickle cell disease is a genetic blood disorder characterized by the sickling of red blood cells, which can block blood vessels and cause severe pain in bones, chest, back, or joints. Vaso-occlusive crises are a major cause of morbidity and reduced quality of life for millions of patients worldwide. Current therapeutic options are limited, creating a significant unmet medical need for effective and well-tolerated treatments.

Novo Nordisk’s development of etavopivat aims to address this gap by providing a novel oral therapy that targets the underlying pathophysiology of SCD. The company’s acquisition of Forma Therapeutics and subsequent Phase 3 success represent a strategic effort to expand treatment options for this patient population.