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New sickle cell drug voxelotor boosts levels of haemoglobin

Presented by
Dr Jo Howard, King’s College London, United Kingdom
EHA 2019
Phase 3, HOPE
Results from the randomised, placebo-controlled, phase 3 Hemoglobin Oxygen Affinity Modulation to Inhibit HbS Polymerization (HOPE) trial of voxelotor in adults and adolescents with sickle cell disease showed promising effects on anaemia and haemolysis in roughly 60% of patients included [1]. As well as being presented at the EHA meeting, the data were simultaneously published in the New England Journal of Medicine [2].

Dr Jo Howard (King’s College London, United Kingdom) presented new data from the late-stage HOPE trial, which showed that voxelotor, a new treatment for sickle cell disease (SCD), significantly improves anaemia and haemolysis, and provides strong evidence that voxelotor has the potential to be a disease-modifying treatment that could prevent chronic organ damage. SCD is a genetic blood disorder that affects millions worldwide and can cause recurrent pain episodes and chronic anaemia, leading to damaged organs, stroke, and premature death. Voxelotor reversely binds to haemoglobin, stabilising the oxygenated state. This increases haemoglobin oxygen affinity which prevents polymerisation of (otherwise deoxygenated) sickle haemoglobin, ultimately reversing the sickling of previously sickled red blood cells under hypoxic conditions [2].

Patients (n=274) treated with voxelotor in the HOPE study demonstrated robust improvements in anaemia as measured by an increase in haemoglobin after 24 weeks of treatment compared with placebo, and reduced the incidence of worsening anaemia during the study. In addition, voxelotor treatment reduced the amount of haemolysis. However, the researchers reported no significant difference between voxelotor and placebo in the rate of vaso-occlusive crises. The annualised incidence rate was 2.77 and 2.76 with voxelotor dosed at 1,500 mg and 900 mg, respectively, vs 3.19 with placebo. The HOPE trial met its primary endpoint, the percentage of patients with a haemoglobin response, at least at the 1,500 mg voxelotor dose.

Haemoglobin response was defined as an increase of more than 1g/dL at week 24 in the intention-to-treat analysis; 59.5% of patients in the 1,500 mg group met this benchmark vs 9.2% in the placebo arm, which was statistically significant with a P-value less than 0.001. Meanwhile, 38% of patients in the 900 mg group had a haemoglobin response. The study’s authors said longer-term follow-up was needed, and added that an analysis at 72 weeks was planned, as well as an open-label extension trial of voxelotor’s long-term effects.

    1. Howard J, et al. Abstract S147, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.
    2. Vichinsky E, et al. N Engl J Med. 2019 Jun 14.


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