Oxbryta Trial for SCD Patients Reports Death Cases, 8 Out of 236 Participants Die, FDA Urges Not to Discontinue Treatment!

Doppler ultrasound measurement has a significant impact in medical research. The study focused on clinical data from 236 patients in Egypt, Ghana, Kenya, Nigeria, Oman, Saudi Arabia, the United States and the United Kingdom. Specifically, in the Phase III GBT440-032 trial, patients treated with Oxbryta experienced more frequent vascular occlusion crises (VOCs) than those treated without Oxbryta, and unfortunately eight deaths were recorded.

As one of the most common acute complications in patients with SCD (sickle cell disease), the severity of VOC cannot be ignored. SCD, as a hereditary blood disorder, has a core pathology in which glutamate, the sixth amino acid in the β-peptide chain, is replaced by valine, which leads to the production of abnormal hemoglobin, sickle hemoglobin (HbS). The presence of HbS causes red blood cells to deform (sickle) and even destroy, and this abnormal form of red blood cells not only has a short life span, but also is easy to block small blood vessels, resulting in pain, breathing difficulties, hemolysis and a series of complex symptoms and complications.

Oxbryta, as the first drug approved by the FDA to directly inhibit HbS polymerization, its mechanism is to effectively inhibit the polymerization process of HbS by improving the affinity of hemoglobin to oxygen, thus reducing the degree of deformation and destruction of red blood cells.

In addition, a second trial, GBT440-042 (also known as RESOLVE/NCT05561140), which investigated Oxbryta for leg ulcers in 88 12-year-old patients enrolled in Brazil, Kenya, and Nigeria, reported eight deaths in its open-label phase.

Of note, the Phase III GBT440-038 trial (NCT04188509), which was scheduled to evaluate the long-term safety of Oxbryta and its efficacy in improving SCD-related complications in participants who completed treatment in earlier clinical studies, has been suspended.

In response to the deaths in the trial, the European Medicines Agency (EMA) stated that there is no conclusive evidence that Oxbryta directly caused the deaths of patients. Given that most of the patients involved are from Africa, it cannot be ruled out that some of the cases are related to infectious diseases such as malaria.

In light of the above, the U.S. Food and Drug Administration (FDA) has issued an official bulletin urgently urging patients and healthcare providers not to discontinue treatment and advising providers to suspend prescribing Oxbryta. At the same time, patients who have taken the drug should immediately contact their health care provider to discuss and adjust treatment options.

As a rare disease with autosomal dominant inheritance, SCD has been included in the first Rare Disease Catalogue in China. Its medical history dates back to the first reported case in 1910 by American physician James B. Herrick, which detailed a 20-year-old patient from Jamaica with a distinctive "sickle" or "crescent" shape of red blood cells.

In 1949, a landmark study by E. Anthony Beutler and James V. Neel revealed the genetic nature of SCD and its pathological mechanism driven by mutations in a single gene. Subsequent studies further elucidated the genetic pattern of SCD and its potential protective effect against malaria infection.

SCD usually develops in early childhood, and the severity of the condition varies from person to person. At present, treatment strategies mainly include blood transfusion and drug therapy. Among them, hydroxyurea as the first drug approved by the FDA for the treatment of SCD, its development history and efficacy have been widely recognized. In addition, with the advancement of medical technology, a variety of new drugs, including Oxbryta, as well as gene therapies such as Casgevy and Lyfgenia, are gradually being applied to the clinic, providing patients with more treatment options. However, considering the limited scope and high cost of gene therapy, its application in the field of SCD therapy still needs to be further evaluated and explored.