By Matthew Willett

Celgene Corp. plans to aim its Thalomid at metastatic colorectal cancer in a trial that will team thalidomide, as Thalomid is generically known, with a Camptosar (irinotecan) and 5-fluorouracil/leucovorin (5-FU/LV) regimen.

The company¿s plan to initiate a Phase II trial in that indication is the latest step in a long journey for Thalomid, which began its therapeutic life as a sedative. It¿s now in more than 150 clinical trials in cancer and inflammatory diseases, some of which could lead to commercialization, Celgene¿s president and chief operating officer, Sol Barer, told BioWorld Today.

¿We¿re preparing to submit [a new drug application] to the FDA by the end of the third quarter in refractory multiple myeloma,¿ Barer said. ¿In addition to that, there are about 150 clinical trials ongoing, and about two-thirds of those are in cancer ¿ various hematological cancers and solid tumors. Part of the rationale is not only trying to understand Thalomid itself and its clinical potential, but also because we¿re developing a new series of compounds based on Thalomid¿s activity, and, hopefully, therapies having the beneficial effect of the drug and reducing the detrimental effects.¿

Celgene will run the Phase II safety and efficacy trial through an agreement with Pharmacia Corp., of Peapack, N.J. In its August 12, 2000, issue, The Lancet published an interim analysis from a pilot study evaluating Thalomid with Camptosar and 5-FU/LV in patients with previously untreated metastatic colorectal cancer.

Thalomid is approved for treatment of acute cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). When birth defects began to plague children whose mothers had used Thalomid as a sedative for morning sickness in the 1950s it was pulled from the market. Later, its utility in treatment of ENL was recognized, and Celgene received marketing approval in that indication in 1998.

Though scientists are still seeking a concrete explanation for Thalomid¿s mechanism of action, some clues have emerged. ¿We do know some of the immunological effects of the drug,¿ Barer said. ¿It lowers TNF-alpha [tumor necrosis factor-alpha] levels; IL-10 [interleukin-10] levels are raised. The drug has antiangiogenic activity,¿ he said.

Though too numerous to cite completely, Barer said programs for Thalomid nearing the end of development are high on Celgene¿s priority list.

¿The ones that I would highlight are in metastatic renal cell cancer, a cancer for which there are not many alternatives for treatment,¿ he said. ¿There¿s a 220-patient Phase III study ongoing, and we¿re looking at initiating a major trial that potentially could lead to approval in that indication.

¿Another indication, of course, is multiple myeloma, and we have various trials looking at refractory patients as well as using it as a first-line treatment as well as in combination with other chemotherapies,¿ he added.

Barer said Celgene also is pursuing programs evaluating Thalomid in myelodysplastic syndrome, colorectal cancer and prostate cancer. The company is considering, he said, initiating a registration trial for MDS with about 200 patients.

¿There¿s a significant amount of interest in the compound in the medical community,¿ Barer said. ¿There are a lot of trials being followed.¿

Evidently, the investment community is watching, too. Celgene¿s stock (NASDAQ:CELG) rose $2.94 Thursday, or 15 percent, to close at $22.41.

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