Oxbryta - referral

Current status

European Commission final decision

Overview

EMA confirms suspension of sickle cell disease medicine Oxbryta.

Higher rate of death and disease complications in recent trials means benefit-risk balance no longer favourable.

Background

On 16 October 2025, EMA’s human medicines committee (CHMP) recommended that the marketing authorisation of the sickle cell disease medicine Oxbryta remain suspended. This recommendation followed interim measures taken by the Committee in September 2024, when it temporarily suspended the medicine to review emerging safety data.

Following its assessment, the CHMP concluded that the benefits of the medicine no longer outweigh its risks. The review was started after data showed a higher number of deaths with Oxbryta than with placebo (a dummy treatment) in one clinical trial¹ and a higher-than-anticipated number of deaths in another trial².

In the first study, which assessed the effect of Oxbryta in people with sickle cell disease who were at higher risk of stroke, 8 children treated with Oxbryta died, compared with 2 children who received a placebo treatment. In the second study, which evaluated the effect of the medicine on leg ulcers, a known complication of sickle cell disease, 1 person died in the Oxbryta group during the first 12 weeks of treatment, while no deaths occurred in the placebo group. In the following 12-week phase of the study, where all patients received Oxbryta, 8 additional deaths were reported. 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.

On 26 September 2024, the CHMP recommended suspending the marketing authorisation as a precautionary measure when further data from two registry-based studies emerged, indicating that patients experienced a higher frequency of sudden pain episodes with Oxbryta than before starting treatment. At the time, EMA provided advice to healthcare professionals and patients, highlighting that Oxbryta should no longer be prescribed and that existing patients should be switched to an alternative treatment³.

Although the final analysis of the registry studies did not confirm an increase in sudden pain episodes with Oxbryta, the recent clinical trials did show more sudden pain episodes and deaths. These results were inconsistent with those of the earlier main clinical trial that supported Oxbryta’s authorisation, which had not shown a difference between treatment groups. 

In its review, the CHMP noted that the underlying mechanisms for the increased number of deaths and complications, including sudden pain episodes, following treatment with Oxbryta in the studies remain unclear. The CHMP found no clear explanation for the increased risks and could not identify measures to effectively minimise these risks or any subgroup of patients for whom the medicine’s benefits would outweigh its risks. As a result, the CHMP concluded that the benefit-risk balance of Oxbryta is no longer favourable, and the suspension of the medicine’s marketing authorisation should remain in place. Oxbryta will therefore remain unavailable for healthcare professionals to prescribe to patients in the EU.

In reaching its opinion, the CHMP also took into account advice from experts in the field as well as from patient representatives and consulted EMA’s safety committee (PRAC) on potential risk minimisation measures. 

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¹ Global Blood Therapeutics. GBT440-032 Phase 3 Study in Participants with Sickle Cell Disease (HOPE Kids 2). IRAS ID: 242661. EudraCT Number: 2017-000903-26. REC Reference: 18/LO/0359. London - City & East Research Ethics Committee. Health Research Authority. Available at: https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/gbtt440-032-phase-3-study-in-participants-with-sickle-cell-disease

² A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy of Voxelotor for the Treatment of Leg Ulcers in Patients with Sickle Cell Disease (RESOLVE). EudraCT Number: 2025-000161-87. ClinicalTrials.gov Identifier: NCT05561140. Available at: https://www.clinicaltrialsregister.eu/ctr-search/trial/2025-000161-87/3rd

³ https://www.ema.europa.eu/en/documents/referral/oxbryta-article-20-procedure-suspension-sickle-cell-disease-medicine-oxbryta_en.pdf

More about the medicine

Oxbryta was authorised in February 2022 to treat haemolytic anaemia (excess breakdown of red blood cells) in patients aged 12 years and older who have sickle cell disease. It was given on its own or together with another medicine for sickle cell disease called hydroxycarbamide. Oxbryta contains the active substance voxelotor.

Sickle cell disease is a genetic disease where individuals produce an abnormal form of haemoglobin (the protein in red blood cells that carries oxygen). The red blood cells become rigid and sticky and change from being disc-shaped to being crescent-shaped (like a sickle).

More about the procedure

The review of Oxbryta was initiated on 29 July 2024 at the request of the European Commission, under Article 20 of Regulation (EC) No 726/2004.

The review was carried out by the Committee for Medicinal Products for Human Use (CHMP), responsible for questions concerning medicines for human use, which adopted the Agency’s opinion.

The CHMP opinion was forwarded to the European Commission, which issued a final legally binding decision applicable in all EU Member States on 9 December 2025.

Oxbryta Article-20 procedure - EMA confirms suspension of sickle cell disease medicine Oxbryta

Reference Number: EMA/298985/2025

Key facts

About this medicine

• Approved name:
  Oxbryta
• International non-proprietary name (INN) or common name:
  voxelotor
• Associated names:
  Oxbryta
• Class:
  Haemoglobin S (HbS) polymerization inhibitor

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-20/1538/C/004869/0014
• Type:
  Article 20 procedures

  This type of procedure is triggered for medicines that have been authorised via the centralised procedure in case of quality, safety or efficacy issues.

• Authorisation model:
  Centrally authorised product(s)
• Decision making model:
  CHMP-EC

Key dates and outcomes

• CHMP opinion date:
  16/10/2025
• EC decision date:
  09/12/2025

All documents

Procedure started

Oxbryta Article-20 procedure - CHMP list of questions

Oxbryta Article-20 procedure - Notification

Oxbryta Article-20 procedure - Timetable for the procedure

Reference Number: EMA/CHMP/348132/2024 rev.6

Oxbryta Article-20 procedure - Review started

Reference Number: EMA/351008/2024

Under evaluation

Oxbryta Article-20 procedure - Assessment report on temporary measures

Adopted Reference Number: EMA/460760/2024

Oxbryta Article-20 procedure - Suspension of sickle cell disease medicine Oxbryta

Reference Number: EMA/464087/2024

Opinion provided by Committee for Medicinal Products for human Use

Oxbryta Article-20 procedure - EMA confirms suspension of sickle cell disease medicine Oxbryta

Reference Number: EMA/298985/2025

European Commission final decision

Oxbryta Article-20 procedure - Annex I - Scientific conclusions

Oxbryta Article-20 procedure - Annex II - Conditions for lifting the suspension of the marketing authorisation

Oxbryta Article-20 procedure - Assessment report

Adopted Reference Number: EMA/354175/2025

Oxbryta Article-20 procedure - EMA confirms suspension of sickle cell disease medicine Oxbryta

Reference Number: EMA/298985/2025

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.