Novo Nordisk is set to begin a Phase 3 clinical trial in December for etavopivat, a once-daily oral drug for sickle cell disease, following encouraging results from its Phase 2 HIBISCUS trial. The global study is designed to further evaluate the efficacy and safety of etavopivat in reducing the frequency of vaso-occlusive crises (VOCs), a hallmark of sickle cell disease.
The decision to move forward with Phase 3 comes after the Phase 2 trial demonstrated a significant reduction in pain crises among patients treated with etavopivat. The HIBISCUS trial, involving 60 participants, compared two dose levels of etavopivat (200 mg and 400 mg) against placebo over a one-year period. Patients were allowed to continue their standard treatments at stable doses during the study.
Phase 2 HIBISCUS Trial Results
The results from the HIBISCUS trial, presented at the ASH annual meeting, revealed that both the 200 mg and 400 mg doses of etavopivat led to an approximate 46% reduction in the rate of pain episodes compared to placebo. Specifically, patients receiving the high and low doses of etavopivat experienced yearly rates of 1.06 and 1.07 pain episodes, respectively, while the placebo group had a rate of 1.97 episodes per year.
Mechanism of Action
Etavopivat functions as a pyruvate kinase activator. Pyruvate kinase is an enzyme present in red blood cells that plays a crucial role in energy production. By activating this enzyme, etavopivat aims to modify red blood cell characteristics, increasing their affinity for oxygen and reducing the likelihood of sickling. This mechanism has the potential to address the underlying pathophysiology of sickle cell disease.
Safety Profile
The safety profile of etavopivat in the Phase 2 trial was generally favorable. Adverse events were predominantly reported as mild to moderate and resolved without intervention. There were isolated cases of increased liver enzymes in the low-dose group and hemoglobin decrease in the high-dose group, both potentially related to the drug. Insomnia was reported by three participants in the 400 mg dose group.
Acquisition and Future Plans
Novo Nordisk acquired etavopivat as part of its $1.1 billion acquisition of Forma Therapeutics in 2022, signaling the company's commitment to expanding its portfolio beyond diabetes and obesity treatments. The initiation of the Phase 3 trial underscores Novo Nordisk's confidence in etavopivat's potential to address the unmet needs of individuals living with sickle cell disease.
