Investigation explores how an $80,000 a year drug was approved for primary progressive form of MS despite concerns over its safety and effectiveness
The US Food and Drug Administration (FDA) is reviewing a petition to revoke the approval of Roche's top-selling drug ocrelizumab (Ocrevus) for treating primary progressive multiple sclerosis (PPMS) – a form of MS thought to affect around 15% of patients.
The petition alleges that the drug was approved despite internal concerns about a lack of effectiveness in women and a potential increased risk of breast cancer.
An investigation published by The BMJ today explores details of the drug's approval and questions whether ocrelizumab could be doing more harm than good in women with this condition.
Kaylin Bower, an MS patient advocate, triggered the FDA's review after being left "absolutely shocked" from reading lengthy review memos written by the FDA scientists who evaluated the manufacturer's application, several of whom recommended against approving ocrelizumab for PPMS.
After reviewing ocrelizumab's trials, one found the results "not persuasive," while others highlighted the drug's "near zero efficacy" for some patients, and an "unusual imbalance" in breast cancer cases. Reviewers also expressed concerns about potential data integrity problems at clinical sites and issues with manufacturing quality.
Despite these warnings, Billy Dunn, the FDA's top neuroscience official at the time, approved the drug for both sexes, opting not to seek the advice of its external advisory committee and directing that breast cancer be noted on product labelling and evaluated in an observational study after ocrelizumab's approval.
But experts warn that the drug's value in treating PPMS has been oversold and point out that the safety study on breast cancer risk is not due to report until late 2030.
Others say that without compelling data to support long term treatment, approval should be narrowed to short term use in patients seen to benefit, and that the drug's benefit in PPMS seems limited to those with active disease.
Roche defends its drug's safety and long term benefit, citing unpublished data which they claim refutes previous sex based disparities.
The company told The BMJ that it had been closely monitoring cases of malignancy, including breast cancer, and that its analysis "did not reveal any new safety signal or safety concern." But it declined to share interim breast cancer data, citing a publication embargo.
After the 2017 approval of ocrelizumab, Dunn oversaw two controversial Alzheimer's drug approvals: aducanumab in 2021, despite reviewer opposition, resignations, and a Congressional investigation finding that FDA's process was "rife with irregularities," and lecanemab in 2023, amid concerns over an unacceptable balance of benefits and harms.
Dunn left the FDA in 2023 to join Prothena, a biotech company developing Alzheimer's treatments.
The approval of ocrelizumab for PPMS, and subsequently aducanumab and lecanemab, all under FDA programmes meant for drugs with the potential to tackle an "unmet medical need," raise questions about whether the system is working as intended.
