Pfizer announced the global withdrawal of its sickle cell disease (SCD) therapy Oxbryta (voxelotor) after identifying safety concerns in its clinical trials program. The company cited an "imbalance in vaso-occlusive crises and fatal events" that requires further assessment, leading to the conclusion that the overall benefits no longer outweigh the risks in the approved patient population.
The withdrawal affects all 35 countries where Oxbryta had been launched, including the United States and Europe. Pfizer has initiated a recall of all distributed lots and suspended ongoing clinical trials while conducting a comprehensive safety review.
"The safety and well-being of patients is of the utmost importance to Pfizer, and we believe this action is in the best interest of patients," said Aida Habtezion, Pfizer's chief medical officer and head of worldwide medical and safety. "Our primary concern is for patients who suffer from SCD, which remains a very serious and difficult-to-treat disease with limited treatment options."
A Significant Therapeutic Loss
Oxbryta represented a breakthrough in SCD treatment as the first medication approved that directly prevented sickle hemoglobin (HbS) polymerization, the molecular basis of sickling and destruction of red blood cells in the disease. The drug received FDA approval in 2019 for patients aged 12 and older, with an expanded indication in the US to include children as young as four years old.
The European Commission granted approval for Oxbryta in 2021 for patients aged 12 and above, allowing its use either as monotherapy or in combination with hydroxyurea, a well-established SCD treatment.
The drug had shown promising commercial performance, with sales increasing 73% to reach $328 million in 2022. Pfizer had projected peak annual sales exceeding $2 billion, highlighting the significant market potential that has now been curtailed.
Impact on Patients and Pfizer's Investment
Sickle cell disease affects approximately 52,000 people in Europe alone and is particularly prevalent among those with ancestry from sub-Saharan Africa, though it also affects individuals of Hispanic, South Asian, Southern European, and Middle Eastern descent.
The disease causes red blood cells to become rigid, sticky, and crescent-shaped, impairing oxygen transport throughout the body. This leads to severe complications including painful vaso-occlusive crises, stroke, and irreversible organ damage.
The withdrawal represents a substantial setback for Pfizer, which acquired Global Blood Therapeutics (GBT) for $5.4 billion in 2022 largely based on Oxbryta's potential and the promise of inclacumab, another SCD therapy in development.
Regulatory Warning Signs
The decision doesn't come as a complete surprise to regulatory observers. The European Medicines Agency (EMA) had launched a safety review of Oxbryta in July following reports of fatalities in clinical trials. This review likely contributed to Pfizer's decision to withdraw the drug globally.
Limited Treatment Landscape
The withdrawal of Oxbryta further narrows the already limited treatment options for SCD patients. Novartis' Adakveo (crizanlizumab), an antibody therapy for preventing vaso-occlusive crises, has also faced challenges, having been withdrawn from the European market after failing to reduce crises in a confirmatory Phase 3 trial, though it remains available in the US.
More recently, gene therapies have entered the SCD treatment landscape, including Vertex Pharmaceuticals' Casgevy and bluebird bio's Lyfgenia, both autologous cell therapies targeting the underlying genetic defect. However, these treatments are extremely expensive and access remains limited for many patients.
Financial Implications
The withdrawal represents a significant financial blow to Pfizer. Beyond the immediate loss of Oxbryta's $328 million in annual sales, the company faces questions about the value of its $5.4 billion acquisition of GBT, which was largely predicated on Oxbryta's market potential.
Pfizer has advised patients currently taking Oxbryta to contact their physicians to discuss alternative treatment options while the company continues its investigation into the safety concerns. The Sickle Cell Society has described the withdrawal as a significant setback for patients who already face limited therapeutic choices.
As the investigation continues, the SCD community awaits further information on the specific safety concerns identified and whether Oxbryta might eventually return to market with modified indications or additional safety monitoring.
