Sixteen patients dosed with Pfizer’s sickle cell disease drug Oxbryta® (voxelotor) in a pair of clinical trials have died, European regulators disclosed hours before Pfizer said it was voluntarily withdrawing Oxbryta in the United States and all other markets where it has been approved.
Pfizer cited deaths and vaso-occlusive crises occurring in patients given Oxbryta in clinical studies in announcing the voluntary withdrawal. The pharma giant also said it was halting all clinical trials of the drug as well as its expanded access programs worldwide.
Data from the totality of clinical studies had shown that Oxbryta’s benefits no longer outweighed its risk to patients, Pfizer added.
“The data suggest an imbalance in vaso-occlusive crises and fatal events which require further assessment,” Pfizer said in a statement that offered no specifics on the incidents.
However, the European Medicines Agency (EMA) disclosed findings from two Phase III trials of Oxbryta in which a total of 18 deaths occurred—all but two of them reported in patients who were dosed with the drug.
In the Phase III GBT440-032 trial (also known as HOPE Kids 2; NCT04218084), data showed eight deaths occurring in patients dosed with Oxbryta compared with two patients dosed with placebo.
GBT440-032 had been designed to evaluate the effects of voxelotor on the transcranial doppler ultrasound measurements of cerebral arterial blood flow in children from 2 to 15 years of age who have SCD and are at high risk of stroke. The study recruited 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 portion of the study: “The total number of deaths was higher than anticipated,” the EMA reported.
GBT440-042 had been assessing the effects of voxelotor on leg ulcers in 88 patients from 12 years of age recruited from Brazil, Kenya, and Nigeria.
Also affected by the halt in clinical trials is a third Phase III trial, GBT440-038 (NCT04188509), an open-label extension study designed to assess the safety of, and SCD-related complications of, long-term treatment with voxelotor in participants who had completed treatment in an earlier clinical study.
Information “still being awaited”
The EMA cautioned, however: “There is currently no clear evidence that Oxbryta caused any of the deaths, and information about many of the cases is still being awaited.”
“Some of the cases may have been linked to infections, including malaria,” the agency added.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) was set to discuss Oxbryta on Thursday at an “extraordinary meeting” convened for the purpose.
Pfizer said it has notified regulatory authorities about its findings and was withdrawing Oxbryta from the market and ending distribution and clinical studies while further investigating data from the studies.
Pfizer inherited Oxbryta when it acquired the drug’s original developer, Global Blood Therapeutics (GBT), for $5.4 billion, a deal completed in October 2022. At the time, Pfizer said the deal was intended to complement and further enhance its 30-plus year heritage in rare hematology and reinforce its commitment to treating SCD, for which GBT had been marketing Oxbryta since its approval by the FDA in 2019.
GBT’s president and CEO Ted W. Love, MD, discussed the development of Oxbryta on GEN’s “Close to the Edge” interview series in 2021. The interview touched on the sad history of disdain 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 before an audience of investors in 2020.
Love is now chairman of the Biotechnology Innovation Organization (BIO).
Oxbryta generated $338 million in worldwide sales last year, more than quadruple the $73 million reported by Pfizer alone for 2022 after it acquired GBT. The drug racked up another $176 million during the first half of this year, up 19% from $148 million in January–June 2023.
Last December, the FDA approved two additional treatments for SCD—Casgevy™ (“exa-cel” or exagamglogene autotemcel), the first agency-approved CRISPR-based gene editing therapy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics; and Bluebird Bio’s lentiviral therapy, Lyfgenia™ (“lovo-cel” or lovotibeglogene autotemcel).
