SCDAA Medical and Research Advisory Committee (MARAC) Statement: Pfizer’s Voxelotor (Oxbryta®) Withdrawal
9/27/24
What is the news?
Pfizer announced the withdrawal of voxelotor (Oxbryta®) from national and global markets on September 25, 2024. Clinical research was also stopped. “Pfizer’s decision is based on the totality of clinical data that now indicate the overall benefit of OXBRYTA no longer outweighs the risk in the approved sickle cell patient population. The data suggest an imbalance in vaso-occlusive crises and fatal events, which require further assessment.” [1].
What is the reason?
The Pfizer statement mentions that worrisome new information came from three reports that link voxelotor with more pain and deaths:
- A clinical research study of children with sickle cell disease and with higher risk of stroke (GBT440-032) had eight deaths in the voxelotor group compared to two deaths in the group without voxelotor. The study recruited 236 children (2y-15y) from Egypt, Ghana, Kenya, Nigeria, Oman, Saudi Arabia, USA and the United Kingdom.
- Another clinical research study of adolescents and adults with sickle cell disease and leg ulcers (GBT440-042) had eight deaths on voxelotor. Eighty-eight patients at least 12 years of age were enrolled in Brazil, Kenya and Nigeria.
- Monitoring reports from people taking voxelotor as a prescribed medication, not on a clinical research study. No numbers were listed.
Following standard rules when new risks are found, Pfizer voluntarily withdrew voxelotor from use worldwide, while further investigation is conducted. Pfizer also reports that they are halting manufacturing production and clinical research.
What if I have been doing well on voxelotor (Oxbryta®)?
The FDA has received questions about whether to allow some individuals living with sickle cell disease to continue voxelotor on a “compassionate use” basis. However, for now we cannot assume that “compassionate use” will be allowed.
Do I just throw away the voxelotor?
For people with sickle cell disease who have been on voxelotor and doing well, MARAC does not have evidence on what will happen when you stop taking the medication. There is a report that going from full-dose voxelotor to completely stopping taking the drug led to intense hemolysis (breakdown of red blood cells) and severe sickle cell problems within three days that injured the kidneys and other organs and required hospital care. Thus, many doctors are suggesting that people taper off voxelotor over a period of about two weeks. However, tapering is optional and not based on strong clinical evidence. We strongly urge individuals to discuss their options and next steps with their sickle cell health care professional.
What if I have unusual problems as I discontinue voxelotor?
Contact your sickle cell health care provider. Voxelotor acts by slowing down the breakage of red blood cells (hemolysis) and blocking the red cells from changing to the sickle shape. A possible problem is that if the hemolysis suddenly increases it may damage the kidneys. Your eyes will probably become more yellow (jaundiced), and your urine will be darker yellow-orange. Tell your doctor if you have brown urine (the color of cola). You will probably need to come in for lab tests and treatment. Immediately seek medical attention if you stop making urine even when you are drinking a lot of water. Comprehensive sickle cell centers and sickle cell health care providers are collecting reports from patients about any new problems experienced when they come off voxelotor.
What about my other sickle cell medicines?
This news is only about voxelotor. Continue taking other medications as prescribed.
What are the alternatives to voxelotor?
In the USA, sickle cell disease severity can be reduced by three other medications approved by FDA:
- hydroxyurea (Droxia®, Siklos®),
- glutamine (Endari®), and
- crizanlizumab (Adakveo®)
Blood transfusions are used for selected problems in sickle cell disease, especially to prevent stroke.
- “top-off transfusions” or simple transfusions
- “exchange transfusions” or erythrocytapheresis
Hematopoietic stem cell transplant (also known as bone marrow transplant) is a cure that requires an:
- HLA-identical (fully-matched) sibling donor, or
- haploidentical (half-matched) related donor, or
- unrelated HLA-matched donor
Two gene therapy approaches can potentially cure sickle cell disease without having to find a donor.
- CasgevyTM (CRISPR/Vertex) or
- LyfgeniaTM (bluebird bio)
MARAC recommends making an appointment to discuss your sickle cell treatment plan with your sickle cell health care provider.
Is this the first time a medication has been withdrawn?
No. Other situations of medication withdrawal from the market have occurred.
- 2004: Merck withdrew rofecoxib (Vioxx) as an arthritis drug.
- 1997: FDA ordered Wyeth to remove the weight-loss medications fenfluramine (Pondimin) and a related drug, dexfenfluramine (Redux) from the market.
- 1961: Chemie withdrew thalidomide as an antinausea drug. 2006 thalidomide was approved for the treatment of plasma cell myeloma.
When will there be more updates?
We do not know. MARAC is following the news as it unfolds. The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) regulations control some of the timing for release of information. SCDAA MARAC is continuing to monitor the situation and will update the community as soon as new information is released.
Pfizer statement, 9/25/24: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-voluntarily-withdraws-all-lots-sickle-cell-disease
Pfizer letter to Health Care Providers, 9/26/24: https://webfiles.pfizer.com/dear-hcp-letter-oxbryta-us-final-092524?cmp=US-21234&campaign=US-21234&identitytype=account&tpn=1532773&LNK=GL_BD3-C2&mkt_tok=MTk1LVVMQy0yMDAAAAGV1F26wnPvgN6fKRyyOgU-kt_3Pa-xaL9I_wa6yP1ROToTo85YnZaSQ98g2cAj9j-cf9xvsubH4Rvs50AWKcAMrA4qw1nLMAsCEbu8-c6PeXuPhg
European Medicines Agency, July 2024: https://www.ema.europa.eu/en/medicines/human/referrals/oxbryta
FDA statement, 9/26/24: https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerting-patients-and-health-care-professionals-about-voluntary-withdrawal-oxbryta-market-due
