Sickle cell anemia community is in uproar after a Pfizer drug is withdrawn from the market

She knew what it meant to be in pain that 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 entire body was shutting down. She couldn't move. Her father had to carry her into the car and put her in the back seat. On the drive to the hospital, she recited verses from the Koran and prayed that she would make it.

It had started last January, just before her 27th birthday, when she called to get a refill of a sickle cell drug called Oxbryta. There was some confusion with their insurers; They didn't want to pay for more pills, so she went without them for a few days. One day, Habib went to the gym and felt more lethargic than usual. The next time, she was in the intensive care unit. She stayed for over a week, her consciousness fluctuating.

On Wednesday, Pfizer announced it was withdrawing the drug from the market – and since then doctors have been scrambling to protect their patients from what Habib suffered. Everyone was caught between two options: taking the drug could endanger patients, but suddenly stopping the drug could also endanger patients.

Hematologists began combing through the files, looking for patients taking the drug and instructing them to wean themselves off it rather than quitting cold turkey. This was not what the company recommended. The company initially made no recommendations. Although others disagreed, for many doctors tapering seemed to be the best way to avoid acute consequences. Other consequences — lower blood oxygen levels, greater distrust 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 learned about the recall on Instagram from a patient advocacy group and was pleased that her sickle cell anemia doctor called her with advice about tapering it , before she had to call the clinic herself. “I'm wondering whether I'm going to take more new FDA-approved medications.”

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 risks and benefits — and new risks emerged. In some patients, the drug appeared to trigger more, rather than fewer, of the pain crises associated with the disease. Some study participants in sub-Saharan Africa or Brazil who took the drug had died. There was no evidence that Oxbryta was necessarily the cause – in some cases malaria or another infection was involved – but Pfizer said there was an “imbalance” in deaths and crises. While further research took place, there were no longer any benefits the risks outweigh the risks.

Stories like Habib's were serious but anecdotal – a pattern that doctors had observed in some, but not all, who had stopped Oxbryta. There was a case report from 2022 about a woman who left 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 who forgot to take their pills or ran out of pills who did not experience this problem. It was hard to say who might or might not get caught up in the spiral if they stopped abruptly now.

On Friday morning, respected specialists from across the country attended a National Alliance of Sickle Cell Centers webinar to find out what to do.

“I strongly believe that voxelotor has great benefits for some people,” said hematologist Julie Kanter, president 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 it benefits and who it harms.”

Weaning was not demonstrated. It wasn't consistent either. It depended on how many tablets a patient had left, as pharmacies could no longer sell them. “Our pharmacists looked at this – again, without data – and just said, 'Yes, from a rank-and-file pharmacist perspective, this is the way to go,” said pediatric hematologist Lewis Hsu, the co-host. “It is completely devoid of any data support. This is just an attempt to do no harm and gently bring people down.”

Before things went wrong, Oxbryta was an extra dose of confidence and control for Habib. When she started taking it in 2019 or 2020, she was doing well. She was in her 20s and had not been hospitalized for sickle cell anemia since she was a child. She had already been taking hydroxyurea, one of the few other medications that might help. But she knew she had to stop if she ever wanted to get pregnant. Improving her blood counts could perhaps make her more resilient.

Sickle cell anemia 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 and prone to binding to others of its kind rather than to the oxygen it was meant to carry. It formed tangles and deformed the red blood cells into sharp crescents instead of looking like filled tubes. These “sickles” scratched the inside of their blood vessels and caused inflammation. They caused blockages that contributed to pain crises, lack of oxygen to the tissues and the sending of a cry for help.

Oxbryta could change the stickiness of hemoglobin, allowing the molecule to bind better to oxygen. This, in turn, could extend the lifespan of red blood cells. Although it was better able to absorb its charge, there were still questions about how and where it could release that charge and how this might translate into an effect that was not only biochemical in nature but also felt.

FDA approval was based on hemoglobin levels and not symptoms. But Habib felt a difference, a little extra boost of 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 breathable zone. At the time, she was studying for the MCAT, and every time she came to, the thought would keep coming to her: “I have to reschedule my test!” Then she would drown again.

After the ordeal was over, restarting Oxbryta felt like too much of a risk – not because of the discomfort that occurred when it was in her body, but because of the difficulties that came with withdrawal. “I don't want to end up in a situation,” Habib said, “where I no longer have access to it and it could happen again. “It's not a guarantee that you can recover from it once, let alone twice.”

Now access is drying up for everyone. “What else do we have to lose?” said Bate, the 34-year-old from Baltimore. “You go to the emergency room, people don’t believe your pain.”

The effectiveness of crizanlizumab, another treatment approved in the last decade, is already being questioned due to conflicting study results. Blood transfusions can be a useful tool – but can sometimes trigger a strong immune reaction. In a subset of patients, hydroxyurea may cause too many side effects 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, its research has long been neglected, and its care has long been marked by racism and stigma. “There are a lot of people in the sickle cell warrior community who have felt like guinea pigs in the past,” Habib said.

This week the feeling can be felt in two ways: on the one hand, in the sense that some patients may have been prescribed a medication that was potentially dangerous, on the other hand, in the sense that some lose something helpful without warning. It wasn't just news about a drug that some people had been taking every day for years; That's how it was introduced, without warning or guidance. A patient advocate said she was too devastated to comment. Another was so shocked that she couldn'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 considered giving up her Oxbryta cold because she had done so before and had no problems. However, she also found the whole thing strangely rushed and wondered whether the drug might end up in the medicine cabinet after all – perhaps for a more specific group. “No two people with sickle cell anemia are the same.”

Jason Mast contributed reporting. This story has been updated to include new comments from Quannecia McCruse, and corrected to correct an error: The effectiveness of crizanlizumab, not L-glutamine, was questioned by conflicting study results.