Celgene Corp. is facing a delay in its new drug application for Thalomid after the FDA said it had to conduct a new trial in a different indication, but one that may be more lucrative over time.

Celgene, of Warren, N.J., will now seek approval of Thalomid (thalidomide) to treat early stage multiple myeloma, forgoing the refractory/relapsed multiple myeloma indication previously considered. Talks are still under way with the FDA, though, said Sol Barer, Celgene president and chief operating officer.

“What we did is discussed a strategy,” Barer told BioWorld Today. “It’s an ongoing discussion, but what we are telling the world is that what we have as a target is approval for the drug in multiple myeloma for up-front therapies.”

That’s both good news and bad, said Jason Zhang, biopharmaceutical analyst with Stephens Inc., of Little Rock, Ark. While it means 24 more months of clinical work, it also could mean a larger patient population.

“We’ve all been projecting that the sNDA will be filed and approval will be in place early next year,” he said. “The change is from the FDA, I think, although none of us were in the meeting and [we] have to rely on what the company tells us. [Celgene] has said the FDA allowed them to use the time to disease progression for newly diagnosed multiple myeloma as a reasonable endpoint.”

Celgene’s stock (NASDAQ:CELG) fell $4.51 Thursday, or 16.2 percent, to close at $23.26.

The FDA had asked for a survival endpoint, an endpoint that takes more time to measure than time to disease progression because of less patient follow-up time, Zhang said. He added that if the FDA indeed green-lights the fresh endpoint for newly diagnosed multiple myeloma patients, then there is no reason why Celgene shouldn’t pursue that indication. It’s a larger market with more revenue potential, he said.

Celgene must now conduct the new trial, which will form the application’s backbone, gather data from the four previous trials, bundle it into a suitable package and deliver it to the FDA.

Although the news chopped value off Celgene’s stock, the company said in a news release the delay would not affect its 2002 commercial results. Zhang, however, did not agree.

“We have been saying that with an approval in cancer, it would give [Celgene’s] sales force room to suggest to physicians that they use the drug off label,” he said. “Without that [approval this year], I think the company will be somewhat limited in what it can do with this product.”

Zhang dropped his estimates accordingly. His firm now estimates 2002 Thalomid revenues to be $115.2 million, down from $121.3 million. In 2003, he sees Thalomid bringing in $138.4 million, decreased from $154.3 million.

Thalomid received FDA approval in 1998 for the acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum and as maintenance therapy for prevention and suppression of cutaneous manifestation recurrences. Celgene’s drug has a tremendous moonlighting life it is being evaluated as a potential therapy for cancer in more than 125 clinical studies, the majority of which are independent investigator trials. Celgene itself has designed and submitted a development plan to the FDA for the product in renal cell carcinoma.

Celgene has Revimid, a Thalomid analogue, in Phase II trials for myeloma and solid tumors. It’s a crucial compound, Zhang said, and is next in line in the approval process.

“Longer term, what I think really is going to get people’s confidence back up is whether [Celgene] can take this promise into Revimid,” he said. “Up to today, the thought was to develop Revimid for refractory/relapsed multiple myeloma with the survival endpoint. Now maybe [Celgene] can use Revimid in newly diagnosed multiple myeloma. That would be a big win. But we don’t know if the FDA will agree to that kind of trial.” If so, however, the time to disease progression endpoint might mean that Revimid reaches the market in 2005 or 2006, Zhang added, instead of his former projection of 2007.

Barer said if the discussions with the FDA do produce the time to disease progression endpoint, it “could be a positive precedent,” not only for Revimid, but for Celgene’s other compounds as well.

Celgene’s pipeline includes CDC 801, from its Selective Cytokine Inhibitory Drugs platform, in Phase II trials for Crohn’s disease, and Actimid, in Phase II studies for myeloma patients. Plus there is preclinical work being done, and the company plans to enter the clinic with two more compounds this year, Barer said.

“The company has been doing pretty well, so they just have to regroup and refocus on their pipeline,” Zhang said. “They have a very good pipeline. Hopefully this won’t be such a huge setback for them.”