West Coast Editor
As expected, Celgene Corp. finished its rolling new drug application for Revlimid, asking for the FDA's approval based on Phase II data with the compound for myelodysplastic syndromes (MDS) in transfusion-dependent patients with a 5q-deletion chromosomal abnormality.
Wall Street was unmoved. Celgene's stock (NASDAQ:CELG) closed Friday at $36.42, down 89 cents, possibly because the NDA is based only on earlier-stage data, and investors might be looking with more interest at a different indication for the drug - multiple myeloma (MM).
"We have always maintained our formal guidance on Revlimid has been based on the Phase III [MM] scenario, and a number of analysts model their opinions around that," said Brian Gill, director of public relations for Warren, N.J.-based Celgene.
"At the same time, we've also said that if the opportunity did exist, based on ongoing discussions with the FDA, we'd certainly pursue" approval on Phase II results for the drug against MDS, he added, and "we're very confident that the MDS 5q data package can meet the highest standards that the FDA sets" for Phase II clearance, although he acknowledged the Phase II strategy entails more risk.
Celgene's shares jumped 6 percent Thursday, so any stock price benefit related to the NDA for MDS might have been muted by that rise.
The company said last month that a pair of Phase III trials with Revlimid in MM "overwhelmingly exceeded" the pre-specified efficacy endpoint for stopping the trials. Thalomid (thalidomide), Celgene's approved leprosy drug, already is widely used off label for MM, and formal U.S. marketing clearance for that indication is pending. (See BioWorld Today, March 8, 2005.)
The question is whether the FDA will approve Revlimid on Phase II data against MDS, or prefer to grant clearance first for MM. Among the MDS skeptics is Christopher Raymond, analyst with Robert W. Baird & Co. in Chicago, who noted the filing for Revlimid for MM is not expected until the third quarter, so the launch might not happen until 2006.
Phase III MM studies compared results in patients getting Revlimid (lenalidomide) plus dexamethasone with those given dexamethasone alone for relapsed or refractory MM.
Data from both trials surpassed the p<0.0015 value in the primary endpoint, which is time to disease progression, and Celgene is continuing the trials in order to measure the secondary endpoint, survival.
More detailed MM data are expected when the International Myeloma Workshop is held in Sydney, Australia.
"This will be very detailed and will quantifiably help people understand why the independent monitoring committee decided to unblind the study, contact the FDA and inform them of the results," Gill said.
Raymond wrote in a research note Friday that he "wouldn't be surprised to see [time to MM disease progression] in excess of 12 months" with Revlimid.
"While impressive, we caution against directly comparing this result to single-agent Velcade's seven-month [time to progression] in similar patients," since Revlimid was dosed in combination with dexamethasone, he wrote.
Last fall, the FDA sent Celgene an approvable letter for Thalomid against MM. The company asked for official approval in late 2003, but Thalomid off label has been competing well with Velcade (bortezomib) from Cambridge, Mass.-based Millennium Pharmaceuticals Inc. (See BioWorld Today, Oct. 26, 2004, and March 3, 2005.)
Will Revlimid cannibalize Thalomid? That's less important than finding therapies that work, Gill said.
"Thought leaders keep reminding everybody that [MM] is an incurable disease and more drugs like Thalomid and Revlimid will be needed," he said, predicting that new compounds will be used together and successively. "They will continue to go back into this therapeutic cycle."
MM afflicts about 50,000 people in the U.S., with another 15,000 or so expected to be diagnosed with the plasma cancer this year.
MDS is made up of a group of hematologic malignancies that affect about 300,000 people worldwide, with 10,000 to 20,000 new cases diagnosed each year, given mean survival rates of about 6 months to about 6 years, depending on the disease type. About 20 percent to 30 percent of MDS cases might feature the 5q deletion that Revlimid targets.
"We know that, two-thirds of the time, when an MDS patient is presented with the 5q deletion, if they take a capsule of Revlimid, they become transfusion independent," Gill said - important, since such patients "live week to week off blood transfusions."
More data also will be offered at this year's meeting of the American Society of Clinical Oncology, to be held in May in Orlando, Fla.