Celgene Aims For Fast FDA Approval
Matthew Herper, 07.23.03, 1:20 PM ET
NEW YORK - During its quarterly earnings conference call tomorrow morning, Celgene is expected to describe new clinical trials that could get its experimental cancer drug, Revimid, approved by the Food and Drug Administration more quickly. Until now, the firm has expected to apply for approval based on studies that will not conclude for two years, and expectations have focused on using Revimid to treat multiple myeloma. The new approval strategy will focus on a group of blood malignancies called myelodysplastic syndromes (MDS), and particularly on patients with a specific genetic deletion called 5q- syndrome. So far, all eight patients with 5q- syndrome who were given Revimid in a clinical trial have seen their disease vanish--at least for now.
Chet Hodge, 68, is one of the lucky eight. An aerospace engineer and Navy veteran who earns his living designing rockets, Hodge makes sure to sleep eight hours per night. "I learned a long time ago that when you're tired you become mistake prone," he says. So he was surprised four years ago when he started feeling awfully tired in the afternoons. A hematologist prescribed iron pills, which didn't help. Then, on March 26, 2001, a bone marrow test revealed that he had 5q- syndrome. Like all forms of MDS, the disease causes blood cell counts to plummet. Many patients must subsist on transfusions. Anemia drugs such as Amgen's (nasdaq: AMGN - news - people ) Epogen and Johnson & Johnson's (nyse: JNJ - news - people ) Procrit help a few patients, but generally there is little doctors can do to treat the underlying condition. Yet in a clinical trial currently being conducted at the Arizona Cancer Center, 64% of 25 patients with the disease needed fewer blood transfusions after taking Revimid.
More enticingly, the eight patients with 5q- syndrome, which is caused by a deletion of DNA on the fifth chromosome, saw all signs of their disease disappear after eight months of treatment. They may take Revimid indefinitely, but they no longer need blood transfusions. Moreover, cells with the telltale 5q- chromosome deletion can't be found. The effect is exciting for Warren, N.J.-based Celgene (nasdaq: CELG - news - people ) because it opens up the door for conducting clinical trials in a relatively small number of patients. Novartis' (nyse: NVS - news - people ) Gleevec, the first targeted cancer therapy, was approved after mid-stage trials in which it helped patients with chronic myelogenous leukemia. "For the 5q- people, this behaves almost like Gleevec," says Alan List, the hematologist at the Arizona Cancer Center who conducted the Revimid trials.
Currently, Celgene is enrolling patients for a phase III trial in MDS, List says. Such studies are usually the last step before applying for regulatory approval. Additionally, mid-stage trials in MDS and particularly in 5q- syndrome are continuing. They will be conducted at many cancer centers, not just in Arizona.
When the data are good enough, the FDA sometimes approves a drug based on these trials, as happened recently with Velcade, a Millennium Pharmaceuticals (nasdaq: MLNM - news - people ) drug that treats multiple myeloma. "For all of these trials, the results need to be compelling," says Sol Barer, Celgene's president and chief operating officer. Because MDS sufferers have a high response rate to Revimid, it is possible that appropriate trials could be conducted quickly in relatively small numbers of patients. An accelerated strategy for MDS and multiple myeloma might shave a year off the approval process, Barer says. "We will talk more about it on our conference call," he adds.
In a research note published yesterday, Mark Schoenebaum, a biotechnology analyst at U.S. Bancorp Piper Jaffray, said that Celgene's strategy is a prudent, low-cost attempt to get Revimid approved early. But Schoenebaum sees the chance of an approval before late 2005 as being unlikely. His bank has an investment banking relationship with Celgene.
There are more than 10,000 new cases of MDS diagnosed in the U.S. each year. In about one-third of patients, the disease progresses to become acute myeloid leukemia. Many others suffer for years. Perhaps 250,000 people live with MDS worldwide, many of them subsisting on blood transfusions. Few treatments, aside from bone marrow transplants, could actually stop the disease. The Arizona Cancer Center's List has been treating MDS patients for two decades. "This is certainly the most exciting thing we've ever used," he says.
Although Revimid may behave somewhat like Gleevec, its development couldn't have been more different. It is essentially a targeted cancer drug without a target. Medicines like Gleevec or AstraZeneca's (nasdaq: AZN - news - people ) Iressa are generally developed by looking at a protein that is known to be involved in cancer and designing a drug to block it. Although scientists know that 5q- syndrome is caused by a deletion of DNA, it is not clear which genes are involved in that sequence, according to Michelle LeBeau, a geneticist at the University of Chicago who studies the disease. Revimid, in any case, was designed to be a more potent and safer version of Celgene's existing drug, Thalomid, which was linked to birth defects when used decades ago as an anti-nausea treatment during pregnancy. Thalomid is now widely used to treat multiple myeloma. So far, says Chief Scientific Officer David Stirling, Revimid does not cause such birth defects in New Zealand rabbits--the only animal model in which the Thalomid problem shows up.
Barer says Celgene is open to applying for approval one disease at a time. That could lead to a quandary for doctors who are already prescribing Thalomid for multiple myeloma. The drug was approved in 1998 to treat a skin disease and has never received FDA clearance for myeloma. But with few other options for treating multiple myeloma, which is often fatal within a few years, doctors have used the drug anyway. Would similar off-label use happen if Revimid were approved for another disease? "I hope not," says Kenneth C. Anderson of the Dana-Farber Cancer Institute. "We need to do the trials." Anderson, who is conducting trials with Revimid, spearheaded the trials that resulted in FDA approval of Millennium's Velcade.
Meanwhile, in Mesa, Ariz., Chet Hodge has plenty of energy. He plots his blood counts in Excel and has watched them stay at normal levels for months. He works 40 hours per week, starting each day at 6:30 A.M., and flies model airplanes. Hodge also wants to digitize some audio recordings, including a tape he made 35 years ago of his daughter, then 2 years old, asking his grandmother what Christmas was like when she was a child. He figures if he gets it onto his computer, he can clean up the recording and preserve it. |
