EU agency confirms continued suspension of SCD therapy Oxbryta
Pfizer drug voluntarily withdrawn last year after being linked to deaths
The European Medicines Agency (EMA) has confirmed the continuing suspension of marketing authorization for Pfizer’s sickle cell disease (SCD) treatment Oxbryta (voxelotor) — withdrawn from the market last year due to safety concerns — following a committee’s recommendation that “concluded that the benefit-risk balance … is no longer favourable.”
The EMA’s Committee for Medicinal Products for Human Use (CHMP) had urged the suspension be extended after reviewing its initial recommendation from September 2024. CHMP had at that time recommended the marketing authorization be put on pause after data suggested an increased number of vaso-occlusive crises (VOCs) and deaths among SCD patients taking Oxbryta in post-marketing clinical trials.
Pfizer subsequently voluntarily withdrew Oxbryta from all markets worldwide, and all global clinical trials and expanded access programs involving the oral therapy were discontinued.
“Following its [new] assessment, the CHMP concluded that the benefits of the medicine no longer outweigh its risks,” the EMA said in an agency press release noting the committee’s new recommendation that “the suspension of the medicine’s marketing authorisation should remain in place.”
The CHMP had noted a “higher rate of death and disease complications in recent trials” involving Oxbryta.
Originally developed by Global Blood Therapeutics, now a Pfizer subsidiary, Oxbryta was designed to increase hemoglobin’s ability to bind oxygen. Hemoglobin is the protein inside red blood cells that is responsible for oxygen transport. As such, the treatment worked to prevent the sickling and destruction of red blood cells — SCD’s underlying cause.
Oxbryta was conditionally approved in the U.S. in 2019 for SCD patients aged 12 and older, then extended in 2021 to children as young as 4. Full approval of the therapy in the U.S. was dependent on additional clinical trial data confirming its safety and efficacy.
Oxbryta originally OK’d for use in EU in 2022
In the European Union, Oxbryta was cleared for use in 2022, given either alone or with the standard SCD treatment hydroxyurea for patients 12 and older.
Oxbryta’s approvals were based mainly on positive data from two clinical trials: the Phase 3 HOPE study (NCT03036813) and the Phase 2a HOPE-KIDS 1 trial (NCT02850406). HOPE tested the therapy in individuals with SCD ages 12 to 65, while HOPE-KIDS 1 enrolled younger patients, ages 6 months to 17 years.
In July of 2024, however, the EMA launched an investigation after data from two post-marketing Phase 3 trials — HOPE Kids 2 (NCT04218084) and RESOLVE (NCT05561140) — showed more deaths and other potential complications among treated patients compared with those on a placebo.
[In addition to patient deaths,] the studies … showed a higher number of sudden episodes of severe pain, including vaso-occlusive crises (VOC) among patients treated with Oxbryta compared to those receiving [a] placebo.
In the HOPE Kids 2 trial, which assessed Oxbryta in children with SCD who were at higher risk of stroke, eight children treated with Oxbryta died, compared with two children who received a placebo.
RESOLVE was evaluating the therapy’s impact on leg ulcers in SCD patients, ages 12 and older. In the study’s placebo-controlled phase, one Oxbryta-treated person died, while no deaths occurred in the placebo group. In the following open-label phase, where all patients received Oxbryta, eight additional deaths were reported.
According to the EMA, “the studies also showed a higher number of sudden episodes of severe pain, including vaso-occlusive crises (VOC) among patients treated with Oxbryta compared to those receiving placebo.”
These data were inconsistent with those of the earlier clinical trials that supported Oxbryta’s approval.
Committee found no patient group for whom benefits outweighed risks
In its latest review, CHMP noted that the underlying mechanisms for the higher number of deaths and complications with Oxbryta remain unclear. The committee was also unable to identify measures to minimize these risks, or determine any group of patients for whom the therapy’s benefits would outweigh its risks.
As a result, the CHMP confirmed that Oxbryta will remain unavailable to patients in the European Union. The CHMP’s opinion was supported by SCD experts, patient representatives, and the EMA’s safety committee on potential risk minimization measures, according to the release.
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