She knew what it was like to have pain she couldn’t put into words, but this was worse. As a child, Nana-Bilkisu Habib had felt it in her arms, legs or back, but it was everywhere, as if her whole body was closing down. She couldn’t move. Her father had to carry her into the car and put her in the backseat. She spent the drive to the hospital reciting verses from the Quran, praying that she would get through it.
It had started last January, just before her 27th birthday, when she had called for a refill of a sickle cell drug called Oxbryta. There was some confusion with her insurers; they didn’t want to pay for more pills, so she went without for a few days. One day, Habib went to the gym and felt more lethargic than usual. The next moment she was in intensive care. She remained for more than a week, consciousness wavering.
On Wednesday, Pfizer announced it would pull the drug from the market — and since then, doctors have been trying to protect their patients from what Habib endured. Everyone was caught between two options: taking the drug could endanger patients, but abruptly stopping the drug could also endanger patients.
Hematologists began scouring files, looking for patients who were taking this drug, and instructing them to wean themselves off instead of quitting cold turkey. That was not what the company recommended. The company had no immediate recommendations. Although others disagreed, tapering seemed to many doctors to be the best way to prevent acute consequences. Other consequences – less oxygen in the blood, more distrust of the medical system – would take longer to figure out.
“I feel like a test dummy right now,” says Aldoris M. Bate, a 34-year-old financial analyst in Baltimore who heard about the recall on Instagram from a patient advocacy group and was glad her sickle cell disease doctor called her with tapering advice before she tried the recall herself. clinic had to call. “I’m second-guessing myself about taking any more new, off-the-shelf drugs from the FDA.”
Doctors and patients felt there was a lack of data on all fronts.
The concerns behind the withdrawal were serious. The Food and Drug Administration approved Oxbryta in 2019, but data collection and clinical trials continued to refine the understanding of its risks and benefits — and new risks had emerged. In some patients, the drug appeared to be associated with more pain crises associated with the condition, not less. Some research volunteers in sub-Saharan Africa or Brazil who had taken the medication had died. There was no evidence that Oxbryta was necessarily the cause – in some cases there was malaria or another infection – but Pfizer said there was an “imbalance” in the number of deaths and crises. While more research took place, there are no more benefits outweighed the risks.
Stories like Habib’s, meanwhile, were serious but anecdotal — a pattern doctors had observed in some, but not all, who stopped Oxbryta. There was a case from 2022 about someone who went out of town without her pills and ended up with multi-organ dysfunction. There were a few other similar cases. On the other hand, doctors have also seen many patients forget to take their pills, or run out, who didn’t have that problem. It was hard to say who would or would not end up in a spiral if they stopped abruptly now.
On Friday morning, respected specialists from around the country clicked into a webinar from the National Alliance of Sickle Cell Centers to try to figure out what to do.
“I am convinced that voxelotor offers many benefits to some people,” says hematologist Julie Kanter, chair of the alliance, using the scientific name for Oxbryta. “I also firmly believe that it causes harm – and that we don’t yet know who benefits and who it harms.”
Weaning has not been proven. It wasn’t uniform either. It depended on how many pills a patient had left, as pharmacies could no longer sell them. “Our pharmacists looked at this – again without data – and just said, ‘Yes, from the pharmacist’s perspective, this is the way to do it,’” said pediatric hematologist Lewis Hsu, the co-presenter. “It is completely without any data support. This is just a way of trying not to cause any damage and gently putting people down.”
Before it became the opposite, Oxbryta meant an extra dose of confidence and control for Habib. When she started using it in 2019 or 2020, she was doing well. She was in her twenties and had not been hospitalized since childhood due to a sickle cell crisis. She was already taking hydroxyurea, one of the few other medications that could help. But she knew she had to stop if she ever wanted to get pregnant. Improving her blood work might make her more resilient.
Sickle cell disease is a disease of hemoglobin, the molecule that carries oxygen throughout the body on board red blood cells. A mutation she inherited made her hemoglobin sticky, making it susceptible to other mutations of its kind, rather than the oxygen it was supposed to carry. It formed clumps, distorting the red blood cells into sharp crescents instead of making them look like padded inner tubes. These ‘sickles’ scratched the inside of her blood vessels and caused inflammation. They caused blockages that played a role in pain crises, deprived tissues of oxygen and sent a signal for help.
Oxbryta could change the stickiness of hemoglobin, allowing the molecule to better link itself to oxygen. That, in turn, could extend the lifespan of red blood cells. While it was able to pick up its payload better, there were still questions about how and where it dropped that charge, and how that might translate into an effect that was not only biochemical but also tangible.
The FDA approval was based on hemoglobin levels and not symptoms. But Habib felt a difference, a little extra energy. Her lab values also shot up, from about 9 grams of hemoglobin per deciliter to about 13, from low to normal.
When she ran out of pills, the hypothesis goes, her hemoglobin abruptly lost its oxygen-carrying capacity, almost like a change in cabin pressure on an airplane, and her body suddenly operated in a less breathing zone. She was studying for the MCAT around that time, and whenever her thoughts swam back into consciousness, the thought that kept coming was, “I need to reschedule my test!” Then she would go down again.
After the ordeal was over, restarting Oxbryta felt like too much of a gamble – not because of the problems that arose while it was in her body, but because of the problems associated with withdrawing it. “I don’t want to be in that situation,” Habib said, “where I no longer have access to it and that could happen again. It’s not a guarantee that you can get rid of it once, let alone twice.”
Now access is drying up for everyone. “What else can we lose?” said Bate, the 34-year-old in Baltimore. “You go to the ER, people don’t believe your pain.”
The efficacy of crizanlizumab, another treatment approved in the past decade, has already been questioned due to conflicting research results. Blood transfusions can be a useful tool, but can sometimes cause a strong immune response. Hydroxyurea may cause too many side effects for a subset of patients to continue taking it. Gene therapy can be a “cure”, but it is not offered or accessible to everyone.
The vast majority of Americans with the disease are black; research has long been neglected and healthcare has long been steeped in racism and stigma. “There are a lot of people in the sickle cell warrior community who historically felt like guinea pigs,” Habib says.
This week the feeling could go both ways, in that some patients may have been prescribed a drug that was potentially dangerous, and in the sense that some may lose something useful without warning. It wasn’t just news about a drug that some people had been taking daily for years; that’s how it was rolled out, with little warning or guidance. One patient advocate said she was too devastated to comment. Another was so shocked that she didn’t believe it at first.
“You know I’m just worried about everyone’s safety. I want to make sure no one has extreme side effects,” said Quannecia McCruse, president and CEO of the Sickle Cell Association of Houston, who this week had considered quitting her Oxbryta treatment cold turkey because she had done so before. did it and had no problems. Still, she also found the whole thing strange, and wondered if the drug might still end up in the medicine cabinet—perhaps for a more specific group. “Not one person with sickle cell disease is the same.”
Jason Mast contributed reporting. This story has been updated with new comments from Quannecia McCruse, and corrected to correct an error: the efficacy of crizanlizumab, and not L-glutamine, has been called into question by conflicting research results.