Celgene is betting on a quick FDA approval of Revlimid in low-risk MDS patients as the fastest way to get the drug into the hands of doctors and, of course, to begin generating revenue from the drug. Patients diagnosed with a low-risk form of MDS represent a small commercial market opportunity. For Celgene, however, the real prize is the use of Revlimid as a treatment for multiple myeloma, a blood cancer. Many people believe that Celgene has been rushing ahead with a Revlimid filing for low-risk MDS to get the drug approved in 2005 so it can then be used off-label by doctors to treat multiple myeloma, which represents a much larger and more lucrative commercial market. Of course, Celgene won't acknowledge this because it is not allowed to promote a drug off-label. The company is conducting pivotal phase III studies of Revlimid in multiple myeloma, with data expected next year. If positive, Celgene says it would file with the FDA for this indication in late 2005, which means the drug would not be approved until 2006. It's not uncommon for patients to die while participating in clinical trials, including patients who die for reasons unrelated to the drug being studied. The specific causes of the deaths in the Revlimid study are not yet entirely clear and won't be until Celgene makes public data from the study. But the deaths are concerning, in any case, because the patients in this study are all diagnosed with a low-grade form of MDS in which parts of the human chromosome 5 are missing. MDS patients with so-called 5q minus deletion have a disease that progresses slowly and generally does not represent a near-term risk of death.
Scale of Risks
The merits of an experimental drug always have to be judged with a scale of risks and benefits in mind. Early data on Revlimid in patients with the 5q minus form of MDS have shown strong efficacy. After taking Revlimid, many of these patients no longer required blood transfusions or red blood cell-boosting drugs to keep the disease at bay. In addition, doctors discovered that patients no longer had cells in their body that were missing the 5q gene sequence. Efficacy data from this current uncontrolled phase II study are expected to show similarly strong results, which Celgene believes will convince the FDA to approve the drug under an accelerated protocol -- that is, without first requiring Celgene to conduct a larger, controlled phase III study. Whether this efficacy benefit outweighs any safety and/or toxicity risk associated with the drug will be a matter for the FDA to decide. In prior studies, for instance, Revlimid has been associated with serious cases of myelosuppression, a condition in which bone marrow activity is decreased, resulting in lower counts of red blood cells, white blood cells and platelets. Patients with myelosuppression more easily succumb to infections. Myelosuppression is a known side effect of many cancer drugs.