Washington Editor

Celgene Corp.'s Thalomid (thalidomide) again is approvable for multiple myeloma, but only after certain conditions are met, the FDA said.

The agency issued an approvable letter for the second time in response to the company's supplemental new drug application for the oncology indication, an area in which the drug has long been used off label. Celgene is intent on resolving any outstanding issues.

"A lot of this is very short term and manageable," Brian Gill, the company's director of public relations, told BioWorld Today. "We're very hopeful for FDA action in the very near term."

The agency is requesting revised product labeling to specify those with newly diagnosed disease as its intended patient population and updated safety information, as well as some additional patient information to finalize its review.

Gill noted that the FDA asked for various pieces of existing information, as Thalomid's label already gets regular safety updates.

The agency also is asking the company to prod principal investigators to complete a few remaining patient files from the study on which the sNDA is based, so the only new component of the approvable letter relates to wording on the label. Indicating that the drug should be solely for newly diagnosed patients, the language would reflect an amendment to the sNDA that is specific to those patients alone.

Gill noted that such newly diagnosed patients represent "the largest piece of the pie," and added that Celgene, of Summit, N.J., would complete its requirements "very, very quickly."

But despite the company's positive view on the FDA's approvable letter, others voiced displeasure. The International Myeloma Foundation's leadership expressed "disappointment" in the agency's decision to "further delay formal approval." Brian Durie, the chairman of the California-based advocacy group and a practicing hematologist/oncologist, noted that Thalomid is well known in medical and patient communities, and added that clearance in multiple myeloma would further legitimize its widespread use in that setting.

"This is a drug that everybody has a lot of experience with, both in terms of the benefit we see in patients [but] also it's a drug that needs to be used with caution," he told BioWorld Today. "But we have, apparently, delays in full approval for this drug, which are superficially puzzling."

Durie was referencing the drug's link to severe birth defects.

The submission is based on results from a randomized Phase III study that compared Thalomid plus dexamethasone to dexamethasone alone in previously untreated multiple myeloma patients. The trial reached statistical significance on its primary endpoint, which was based on response rates, in demonstrating the combination's efficacy. The study included more than 200 patients and was conducted by the Eastern Cooperative Oncology Group (ECOG).

"You'll hear this comment from doctors across the country and around the world," Durie said, "that they're using this drug as an integral part of their armamentarium."

Thalomid first received FDA approval in 1998 for erythema nodosum leprosum, and it can be marketed only under a restricted distribution program called S.T.E.P.S., the System for Thalidomide Education and Prescribing Safety.

It has never received approval for cancer, although off-label use in oncology accounts for most of its sales. In fact, the Thalomid/dexamethasone pairing has become the standard of care in that setting. Gill called it "the most widely prescribed drug for multiple myeloma," with such usage supported by peer-reviewed publications and cancer association treatment guidelines.

Through the end of Celgene's most recent quarter on Sept. 30, nine-month Thalomid sales were up 26.7 percent over the same period in 2004, to $281.9 million.

The company does not disclose what percentage of those sales are attributable to off-label use, but Gill said more than 130,000 patients have been treated with it since approval.

"As Thalomid is already widely used off label in multiple myeloma," Christopher Raymond, an analyst with Robert W. Baird & Co. in Chicago, said in a research note, "we do not think this setback will materially affect Thalomid sales."

Notably, additional data are being released in advance of next month's American Society of Hematology meeting to further detail Thalomid's use across all stages of multiple myeloma and in other cancers. The drug, which has been tested in solid-tumor and blood-borne cancers, is the subject of about 100 investigator-sponsored studies worldwide.

Durie noted that despite Thalomid's popularity in cancer, outright approval would prove critical in further integrating such usage into additional treatment guidelines and reimbursement patterns, in addition to removing any patient fears.

The drug received its first approvable letter about a year ago. Gill said that original application was for general treatment of multiple myeloma, not newly diagnosed patients, so the first approvable letter requested data from the ECOG study. (See BioWorld Today, Feb. 24, 2004, and Oct. 26, 2004.)

Apart from Thalomid, Celgene is awaiting an FDA decision on Revlimid (lenalidomide), a thalidomide analogue that received backing from an advisory panel earlier this year, but a decision was delayed last month. The agency's Oncologic Drugs Advisory Committee had voted 10-5 in favor of approving the drug for myelodysplastic syndromes, and Raymond said that drug has the potential to drive Celgene's growth. (See BioWorld Today, Sept. 15, 2005.)

Gill said the FDA is being "very conservative" in finalizing its review of Revlimid, which he added was "structurally distinct" and "biologically different" from Thalomid. The company already has established a Revlimid risk-management program along the lines of that used with Thalomid, and the delay is attributable to fine details related to Revlimid's eventual distribution.

On Tuesday, Celgene's shares (NASDAQ:CELG) gained 7 cents to close at $59.97.