Pfizer withdraws SCD drug Oxbryta after EMA announces 16 deaths in trials

Sixteen patients treated with Pfizer's sickle cell anemia drug Oxbryta® (voxelotor) in two clinical trials have died, European regulators announced hours before Pfizer announced it was voluntarily withdrawing Oxbryta from the US and all other approved markets.

Pfizer cited deaths and vaso-occlusive crises that occurred in patients given Oxbryta in clinical trials as the reason for the voluntary withdrawal of the drug. The pharmaceutical giant also said it was halting all clinical trials of the drug as well as its expanded access programs worldwide.

Data from all clinical trials have shown that the benefits of Oxbryta no longer outweigh the risks for patients, Pfizer added.

“The data suggest an imbalance in vaso-occlusive crises and fatal events that requires further investigation,” Pfizer said in a statement, which did not provide details of the incidents.

However, the European Medicines Agency (EMA) published results from two Phase III studies on Oxbryta, which resulted in a total of 18 deaths – all but two of which were due to the drug.

In the Phase III trial GBT440-032 (also known as HOPE Kids 2; NCT04218084), data showed that eight deaths occurred in patients who received Oxbryta compared with two patients who received placebo.

GBT440-032 was designed to evaluate the effects of voxelotor on transcranial Doppler ultrasound measurements of cerebral arterial blood flow in children aged 2 to 15 years who have SCD and are at high risk for stroke. The study included 236 patients from Egypt, Ghana, Kenya, Nigeria, Oman, Saudi Arabia, the United States and the United Kingdom.

In a second Phase III trial, GBT440-042 (also known as RESOLVE; NCT05561140), eight deaths occurred in the open-label part of the study: “The total number of deaths was higher than expected,” the EMA reported.

GBT440-042 evaluated the effects of voxelotor on leg ulcers in 88 patients aged 12 years and older from Brazil, Kenya and Nigeria.

The halt in clinical trials also affects a third Phase III trial, GBT440-038 (NCT04188509), an open-label extension study designed to evaluate the safety and SCD-related complications of long-term voxelotor treatment in participants who completed treatment in a previous clinical trial.

Information “is still awaited”

However, the EMA cautioned: “There is currently no clear evidence that Oxbryta caused any of the deaths and information on many of the cases is still awaited.”

“Some of the cases may be linked to infections, including malaria,” the agency added.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) was due to discuss Oxbryta on Thursday in an “extraordinary meeting” convened for that purpose.

Pfizer said it had informed regulators of its findings and was withdrawing Oxbryta from the market and ending distribution and clinical trials while it continued to review data from the trials.

Pfizer inherited Oxbryta when it acquired the drug's original developer, Global Blood Therapeutics (GBT), for $5.4 billion; the deal closed in October 2022. At the time, Pfizer said the deal was designed to complement and expand its more than 30 years of experience in rare hematology and reaffirm its commitment to treating SCD, for which GBT had marketed Oxbryta since its FDA approval in 2019.

GBT's President and CEO Ted W. Love, MD, discussed the development of Oxbryta on GENs “Close to the Edge” interview series in 2021. The interview touched on the sad history of scorn and discrimination faced by SCD patients, most of whom are of African descent, as well as the list price for Oxbryta, which Love defended during the interview and to an audience of investors in 2020.

Love is now chairman of the Biotechnology Innovation Organization (BIO).

Oxbryta generated global sales of $338 million last year, more than four times the $73 million Pfizer reported for 2022 alone after acquiring GBT. The drug brought in another $176 million in the first half of this year, up 19% from $148 million in the January-June 2023 period.

Last December, the FDA approved two additional treatments for SCD: Casgevy™ (“exa-cel” or exagamglogene autotemcel), the first agency-approved CRISPR-based genome editing therapy developed by Vertex Pharmaceuticals and CRISPR Therapeutics, and Bluebird Bio’s lentiviral therapy Lyfgenia™ (“lovo-cel” or lovotibeglogene autotemcel).