She knew what it was 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 or legs or back, but this was everywhere, as if her whole body were shutting down. She couldn’t move. Her dad had to carry her into the car and lay her in the backseat. She spent the drive to the hospital reciting verses of the Quran, praying that she would make it through.
It had started last January, just shy of her 27th birthday, when she’d called to get a refill of a sickle cell drug called Oxbryta. There was some mix-up with her insurers; they wouldn’t pay for more pills, so she went without for a few days. One day Habib was going to the gym, feeling more lethargic than usual. The next she was in the ICU. She stayed for over a week, consciousness wavering.
On Wednesday, Pfizer announced it was pulling the drug off the market — and doctors have been scrambling ever since to protect their patients from what Habib endured. Everyone was caught between two possibilities: Taking the drug might put patients at risk, but abruptly stopping the drug could put patients at risk, too.
Hematologists began combing through files, searching out patients who were on this drug, instructing them to wean themselves off rather than quitting cold turkey. That wasn’t what the company had recommended. The company hadn’t immediately made any recommendations. Though others disagreed, to many doctors, tapering seemed like the best way to avoid acute fallout. Other consequences — lower blood oxygen, higher mistrust of the medical system — would take longer to figure out.
“I feel like a test dummy right now,” said Aldoris M. Bate, a 34-year-old financial analyst in Baltimore, who’d heard about the recall on Instagram, from a patient advocacy group, and was glad her sickle cell doctor called her with tapering advice before she had to call the clinic herself. “I’m second-guessing myself if I’m going to do any more new-off-the-FDA-shelf medicines.”
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 fine-tune the understanding of risks and benefits — and new risks had appeared. In some patients, the drug seemed to be linked to more of the pain crises that are associated with the condition, not fewer. Some study volunteers in sub-Saharan Africa or Brazil who’d been taking the medication had died. There wasn’t evidence that Oxbryta was necessarily the cause — in some cases, malaria or another infection was involved — but according to Pfizer, there was an “imbalance” in deaths and crises. While more investigation took place, benefits no longer 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 report from 2022 about someone who went out of town without her pills and ended up with multi-organ dysfunction. There was a smattering of other, similar instances. Then again, physicians have also seen plenty of patients forget to take their pills, or run out, who didn’t have that issue. It was hard to say who might or might not spiral if they stopped abruptly now.
On Friday morning, well-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 firmly believe that voxelotor benefits some people a lot,” said hematologist Julie Kanter, president of the alliance, using the scientific name for Oxbryta. “I also firmly believe it causes harm — and that we don’t know who it benefits yet and who it causes harm to.”
Weaning wasn’t proven. Nor was it uniform. It depended on how many pills a patient happened to have left, given that pharmacies couldn’t sell them any more. “Our pharmacists have looked at this — again with no data — and just said, ‘Yeah, from a basic pharmacist point of view, this is the way to do it,” said pediatric hematologist Lewis Hsu, the co-presenter. “It’s completely without any data support. This is just a way to try to try not to cause harm and bring people down gently.”
Before it became the opposite, for Habib, Oxbryta was an extra dose of confidence and control. When she started taking it in 2019 or 2020, she’d been doing well. She was in her 20s and hadn’t been hospitalized for a sickle cell crisis since she was a child. She’d already been on hydroxyurea, one of the few other drugs that could help. But she knew she’d have to stop that if she ever wanted to get pregnant. Improving her bloodwork might just make her more resilient.
Sickle cell is a disease of hemoglobin, the molecule that shuttles oxygen throughout the body aboard red blood cells. A mutation she’d inherited made her hemoglobin sticky, prone to catching onto others of its kind and not the oxygen it was supposed to be carrying. It formed tangles, distorting the red blood cells into sharp crescents rather than looking like filled-in inner tubes. These “sickles” scratched on the inside of her blood vessels and caused inflammation. They caused blockages that played a role in pain crises, tissues starved of oxygen and sending out a signal for help.
Oxbryta could change the stickiness of hemoglobin, so the molecule would be better at hitching itself to oxygen. That in turn could extend the lifespan of red blood cells. Though it was better at picking up its cargo, there were still questions about how and where it let that cargo down, and how that might translate into an effect that wasn’t just biochemical but could be felt.
The FDA approval was based on hemoglobin levels, rather than symptoms. But Habib felt some difference, a little extra burst of energy. Her labs also shot up, from around 9 grams of hemoglobin per deciliter to around 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 cabin pressure change on a plane, her body suddenly operating in a less breathable zone. She’d been studying for the MCAT right around that time, and whenever her mind swam back up towards consciousness, the thought that kept coming was, “I need to reschedule my test!” Then, she’d go under again.
After the ordeal was over, restarting Oxbryta felt like too much of a gamble — not because of the trouble that came when it was in her body, but because of trouble that came with its withdrawal. “I don’t want to be put in that situation,” said Habib, “where I don’t have access to it anymore and that could happen again. It’s not a guarantee you can bounce back from 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 into the ER, people don’t believe your pain.”
Already, the efficacy of crizanlizumab, another treatment approved in the last 10 years, has been called into question with conflicting trial results. Blood transfusions can be a useful tool — but can sometimes trigger a strong immune reaction. Hydroxyurea can give a subset of patients too many side effects for them to keep taking it. Gene therapy can be a “cure” but isn’t offered or accessible to everyone.
The vast majority of Americans with the disease are Black, its research long neglected, its care long suffused with racism and stigma. “There’s a lot of people in the sickle cell warrior community where they felt like, historically, they’ve been guinea pigs,” said Habib.
This week, the feeling can cut two ways, in the sense that some patients may have been prescribed a medication that may have been dangerous, and in the sense that some are losing something helpful with no warning. It wasn’t just the news about a drug that some people had been taking daily for years; it was how it was rolled out, with little warning or guidance. One patient advocate said she was too devastated to comment. Another was so shocked she didn’t believe it at first.
“You know I’m just worried about everyone’s safety. I want to make sure no one is having extreme side effects,” said Quannecia McCruse, president and CEO of the Sickle Cell Association of Houston, who had considered quitting her Oxbryta cold turkey this week because she’s done so before and had no issues. Yet she also found the whole thing weirdly precipitous, 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 is like another.”
Jason Mast contributed reporting. This story has been updated to include new comments from Quannecia McCruse, and corrected to fix an error: The efficacy of crizanlizumab, not L-glutamine, has been called into question by conflicting trial results.
