While oncologists have long prescribed Thalomid to multiple myeloma patients for off-label use, the drug might finally get the OK from the FDA for its first cancer indication.

Warren, N.J.-based Celgene Corp. received an approvable letter from the FDA on Friday for its supplemental new drug application submitted in December.

Accelerated approval could be granted in about six to nine months upon submission of data from the completed study E1A100, a large, randomized Eastern Cooperative Oncology Group (ECOG) study that compared Thalomid (thalidomide) plus dexamethasone to dexamethasone alone in previously untreated multiple myeloma patients. The trial included more than 200 patients, and the primary endpoint, based on response rates, reached statistical significance.

"In our original submission we only had a portion of the interim data from that ECOG trial to include in our package," said Brian Gill, Celgene's director of investor and public relations. "Now, the FDA and we are aware that this ECOG Phase III trial is completed and the data are available."

Thalidomide was first used in 1957 as a sedative and to help pregnant European women deal with morning sickness. It later was determined to cause severe birth defects, such as shortened or absent limbs, in 10,000 children born to mothers that took the drug. Thalidomide never made it to the U.S. market and was banned in Europe in 1962.

The drug, however, is an effective anti-inflammatory and anti-angiogenesis agent, and Celgene licensed rights to it from Rockefeller University and from the Children's Hospital in Boston in the early 1990s. The drug gained FDA approval in July 1998 to treat erythema nodosum leprosum (ENL), a severe and debilitating condition associated with leprosy.

"[ENL] truly accounts for the smallest portion of sales," Gill told BioWorld Today. About 90 percent of Thalomid's sales are for cancer-related conditions. "Out of that 90 percent, approximately 72 percent are related to hematological disorders, and the majority - 68 percent or 69 percent - are for multiple myeloma," he said.

Net product sales of Thalomid in the quarter ended Sept. 30 increased 36.7 percent to $78.7 million, as compared with sales of $57.6 million in the third quarter of 2003.

Celgene has not been able to promote Thalomid for multiple myeloma or any other cancer indication. Most physicians learn about the drug's potential benefits through scientific meetings and peer-reviewed journals. The approval to treat ENL required Celgene to create registration and training procedures for all users to decrease the chances of women taking the drug while pregnant or while attempting to become pregnant.

In April 2000, Celgene received a warning letter from the FDA for allegedly promoting Thalomid off-label as a cancer therapy. The letter highlighted two incidents in which Celgene sales representatives used third-party press releases to outline the drug's potential in treating multiple myeloma. (See BioWorld Today, May 8, 2000.)

If Celgene gets final approval, Gill said the company would be able to get a deeper market penetration for Thalomid as a first-line therapy in multiple myeloma, up from a 30 percent penetration to a 60 percent penetration.

"The drug, obviously, has done exceptionally well without a proactive promotion in the field," Gill said. "The bottom line is it is saving lives, which is clear from the medical data that we see and the key opinion leaders that we talk to." He added that it is "an oral drug, which is convenient and helps people to comply."

Celgene's next immunomodulatory drug in the clinic, Revlimid, is slated for an NDA filing in the first quarter of 2005 to treat myelodysplastic syndrome (MDS). The compound also is being studied for multiple myeloma and a subset of MDS. A Phase III trial in metastatic malignant melanoma was halted in April after interim data suggested Revlimid would not show a statistically significant treatment effect. (See BioWorld Today, April 29, 2004.)

While Revlimid is more potent than Thalomid and does not have the serious side effects, Gill said there still is a place for Thalomid in the market because a drug that works for one patient might not work for another.

"We have key opinion leaders coming back to us saying they do not see this drug going anywhere," he said.

Along with the approvable letter granted Friday, the FDA also accepted for review a new drug application for Focalin XR as a treatment for pediatric and adult attention deficit hyperactivity disorder indications. Celgene licensed the worldwide rights, excluding Canada, to Focalin, which is a refined version of Ritalin, and Focalin XR to Basel, Switzerland-based Novartis Pharma AG in exchange for milestone payments and royalties on Focalin and the entire Ritalin family of drugs.

Researchers presented data at the 51st annual meeting of the American Academy of Child and Adolescent Psychiatry showing that Focalin XR (formerly called Focalin LA) is safe and effective and might help people manage ADHD symptoms. One pediatric study showed that Focalin XR extended-release capsules might help treat symptoms for 12 hours. The therapy was generally well tolerated and had adverse events of headache, insomnia and decreased appetite.

Celgene received a $7.5 million milestone payment for Novartis' NDA submission of Focalin XR. Focalin was approved to treat ADHD in 2001. (See BioWorld Today, Nov. 16, 2001.)

Celgene's stock (NASDAQ:CELG) rose 93 cents on Monday to close at $28.99.