A sickle cell drug that was hyped in headlines is now suspected of harming patients

"Landmark victory." "Life-changing." "Transformative." "Paradigm shift." Potentially "revolutionary."

Those upbeat descriptions appeared in headlines about the sickle cell drug Oxbryta (voxelotor) before it was abruptly pulled from the market in late September due to safety concerns.

Pfizer's decision to withdraw the drug - citing an "imbalance" of complications and deaths in patients who were taking it - triggered heartbreak and confusion among patients with sickle cell, their families and physicians.

The setback serves as a reminder of why journalists should avoid hyping new drugs, especially those cleared through the FDA accelerated approval pathway, which permits marketing before complete data are available. The FDA gave Oxbryta accelerated approval in November 2019.

"No drug should be called transformative, landmark, or life-changing until it's been used in many people for sufficient time to identify harms," Georgetown University Medical Center Professor Adriane J Fugh-Berman, M.D., cautioned in an email. Fugh-Berman directs PharmedOut, a research and education project to promote evidence-based prescribing and expose the impact of pharmaceutical marketing.

Amplifying the hype

Suzanne Robotti, founder of the not-for-profit Medshadow Foundation, which researches and reports on drug side effects, agreed that journalists should avoid boosterish language, including terms like "breakthrough," "game-changer," "miracle" and "Holy Grail."

"I personally would use those phrases only in a historical context," Robotti said in an interview. Age-old drugs such as penicillin and Novocain "were indeed game-changers" although researchers had no way of knowing it at the time, she added.

Sticking to neutral language is not new advice, yet many news stories amplified rosy predictions about Oxbryta by drug company executives, patient advocates and physicians at the time it was approved by authorities in the U.S. and the United Kingdom.

By and large, coverage also should have been critical, according to Robotti, who serves as a consumer representative on the FDA Drug Safety and Risk Management Advisory Committee.

Few news stories pointed out that Oxbryta was given a green light on the basis of a single clinical randomized trial of just 274 patients, or that those patients took the drug or a placebo for 24 weeks - not nearly enough time for long-term adverse effects to emerge.

Coverage largely overlooked the use of a surrogate endpoint, elevated hemoglobin levels. Researchers didn't collect data on clinical outcomes that matter to patients such as improved quality of life or greater ability to complete daily tasks.

Dashed hopes

People with debilitating chronic diseases are particularly vulnerable to positive spin about new treatments. Sickle cell, which affects marginalized communities, is a poignant example.

For decades sickle cell anemia, the most severe form of sickle cell disease, "was overlooked in favor of diseases like cystic fibrosis and hemophilia, diseases which saw more funding and a greater number of breakthroughs," Yoram Unguru, M.D., M.S., M.A., a pediatric hematologist and oncologist at the Herman and Walter Samuelson Children's Hospital at Sinai in Baltimore and an associate professor at the Johns Hopkins Berman Institute of Bioethics, said in an email.

When research finally yielded potential treatments, he said, some patients and clinicians "were more than willing to embrace overly optimistic prognostications."

Oxbryta isn't the only FDA-approved treatment for sickle cell that hasn't panned out. Adakveo (crizanlizumab), which was greenlit around the same time, was determined in 2023 to have no clinical benefit.

Along with physicians, journalists have a duty to communicate responsibly about treatments "even if it risks a less 'sexy' headline," Unguru said, adding that "failure to do so results in harm by promoting fear and compounds mistrust of the medical/scientific community."

Advice for covering new treatments for sickle cell

• Report details on the study used for approval:
  • Number of patients in the trial
  • How long patients took the drug
  • Whether a surrogate endpoint was used and if so, whether it was validated
  • Side effects and their frequency.
• Point out that clinical trials used for FDA approval rarely capture all side effects. A study published in 2017 found that a third of drugs had serious safety issues emerge within five years of FDA approval.
• Explain FDA terminology such as "breakthrough" and "accelerated approval," which may mislead consumers about the rigor of evidence. A PharmedOut report recommended that "accelerated approval" be changed to "conditional approval," since drugmakers are obligated to conduct post-approval confirmatory trials to prove that their products are safe and effective.
• Mention alternative treatments.
• Clearly state the potential benefits. New cell-based gene therapies may reduce complications associated with sickle cell anemia but cannot correct existing damage such as bony necrosis or brain damage from stroke, Unguru noted, and some patients will continue to experience pain crises, a hallmark symptom, even after a successful gene therapy.