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FDA documents reveal doubts about GSK blood cancer drug

Food and Drug Administration staff have raised questions about eye-related side effects of GlaxoSmithKline’s experimental drug to treat multiple myeloma, suggesting the agency may not approve it as expected this quarter. The concerns were revealed Friday in briefing documents ahead of a meeting of the FDA’s advisory committee on cancer drugs.GSK’s drug, called belantamab mafodotin, caused severe fatty deposits in the eyes of 44% of patients in clinical trials, many of whom experienced poorer eyesight, according to the documents. Researchers modified doses to reduce the side effects, but the FDA’s reviewers state that this treatment strategy may not be enough.Cancer drugs have often been quickly reviewed in recent years, with only three new therapies evaluated by an advisory committee of the 10 the FDA approved last year. The nine-member expert panel will meet next Tuesday to decide whether belantamab mafodotin’s side effects are tolerable enough to recommend the agency grant approval.

If approved, belantamab mafodotin would be the first drug cleared for market that targets a protein called BCMA, which is expressed on the surface of nearly all malignant cells in multiple myeloma. The drug binds to BCMA, allowing the release of a toxic chemical that kills the cancer cells, an approach similar to that used for established cancer drugs like Roche’s Kadcyla and Seattle Genetics’ Adcetris.

The study GSK is using to support belantamab mafodotin, DREAMM-2, showed treatment led to complete or partial remissions in 31% of the patients who took it at the dose proposed for approval. Patients enrolled in the trial had to have progressed on three or more previous lines of therapy.

Patients who took the target dose survived a median of nearly one year, GSK claims, compared to the six to nine months that patients would normally survive. The FDA, however, disputes that survival assessment because the trial did not include a placebo arm.

Researchers found fatty deposits called keratopathy in the eye exams of 71% of patients treated at the proposed dose, 44% of which were measured as severe, according to the briefing documents. To manage this, GSK has proposed withholding treatment from patients who either have a substantial decline in eyesight or moderate to severe keratopathy, until their symptoms subside.

GSK argues this side effect has been reported with other multiple myeloma drugs, is reversible with dose interruptions, and notes that no patient reported permanent complete vision loss. Some patients were forced to give up certain activities like driving and reading, however.

FDA reviewers, though are concerned that many of the patients with keratopathy did not show symptoms. If undiagnosed, their eyesight could decline or they could experience vision loss before dose interruptions are taken. Frequency, severity, incomplete data on permanent effects and lack of clear treatment interruption guidelines raise questions over approval, the reviewers state.

The first discussion planned for Tuesday’s advisory panel — made up of outside experts in oncology — is whether GSK has gathered enough data on keratopathy for the FDA to make a good judgment on whether it’s safe enough for approval. The committee is scheduled to vote on whether to recommend approval only after that discussion and a fuller discussion of the keratopathy risk.