The Oncologic Drugs Advisory Committee of the US Food and Drug Administration yesterday gave the thumbs up to US drugmaker Celgene’s New Drug Application for Revlimid (lenalidomide), its drug for myelodysplatic syndromes, despite earlier concerns unveiled in a briefing paper.
According to the briefing documents, which were posted on the FDA’s website, a major concern was whether the single-arm trial design of the three studies submitted for the primary indication was appropriate in a heterogeneous disease like MDS. In addition, the Agency questioned whether the eight-week, transfusion-free endpoint would demonstrate clinical benefit.
A further consideration was whether the dose regimen (10mg continuous) would be excessively toxic and whether a reduced regimen should be studied. “A substantial percentage of patients in all three MDS studies had reductions of the initial dose or interruption of dosing because of adverse events,” the brief points out.
Furthermore, according to the Agency, dose reductions and delays as a result of adverse events were common in the trials. In MDS-003, a pivotal Phase II study in transfusion-dependent MDS patients with the 5q deletion, around 80% of patients had to have doses reduced or held, which indicates that the initial dose may by too high for at least half of the patients, the reviewers noted. The advisory committee was also expected to assess risk management plans for Revlimid, and “whether the teratogenic potential of lenalidomide, a thalidomide analogue, had been adequately characterised.”
Revlimid is the first of Celgene's immunomodulatory drug products to reach this stage of development, and if approved by the FDA will join a crop of new treatments for MDS, including Cell Therapeutics' Trisenox (arsenic trioxide) and Pharmion's Vidaza (azacitidine). Also under regulatory review for MDS is MGI Pharma and SuperGen's Dacogen (decitabine), which was filed in the US last year.
MDS, which has a number of characteristics similar to acute leukaemia, affects around 300,000 people worldwide. The most common symptom is severe anaemia, which can require the patient receive multiple blood transfusions. Revlimid has orphan drug status for this indication in both the US and European Union.
According to industry observers, the agent, which holds Orphan Drug status in the USA and Europe, is one of the most eagerly-anticipated new cancer drugs on the verge of approval, and analysts have forecast peak annual sales of $500 million-$1.0 billion.