West Coast Editor
Awaiting a decision from overseas regulators on the chemotherapy booster Genasense for advanced melanoma, Genta Inc. is deciding its next steps in the U.S., after the FDA declared the product non-approvable for chronic lymphocytic leukemia.
Genta's stock (NASDAQ:GNTA) fell 21.6 percent on the news, closing last Friday at 54 cents, down 15 cents.
CEO Raymond Warrell said the firm is "studying the letter very carefully and considering an array of options" for proceeding in the U.S., as company officials try to devise a coherent development program for Genasense.
"That planning is very far along," Warrell told BioWorld Today, and Berkeley Heights, N.J.-based Genta likely will offer details "sometime after the first of the year. Hopefully during that [first quarter of 2007], we'll have favorable news from Europe."
Ren Benjamin, analyst with Rodman & Renshaw in New York, had expected an approvable letter, with the FDA insisting on another Phase III trial evaluating CLL patients who have relapsed from fludarabine therapy.
The company submitted complete responses to questions from the European Medicines Agency and expects word on whether marketing clearance will be granted to Genasense (oblimersen) plus dacarbazine for melanoma.
In May 2004, the FDA's Oncologic Drugs Advisory Committee voted against approval of Genasense in melanoma, and the compound missed its survival endpoint in a Phase III trial, so Benjamin is "cautious" about the drug's chances overseas. (See BioWorld Today, May 4, 2004.)
In September, ODAC turned thumbs down on the compound for CLL, too, voting 7-3 for denial because Genasense's benefit was deemed not substantial enough. If European regulators favor Genasense in melanoma, Genta could partner the drug and raise money.
At the end of September, the firm had cash and cash equivalents of about $40 million, enough to fund operations into the second quarter, by Benjamin's estimate.
In any case, Genta will continue to develop the drug, he said. "They have enough signs of clear activity and clinical benefit that the company will probably want to sit down with the FDA" and figure out what's needed to put Genasense on the market.
Warrell noted that researchers have put "an enormous amount of work into clearly identifying the patient population to maximally benefit" from Genasense when used as a therapy for CLL and melanoma, as well as acute myelogenous leukemia, against which the compound failed in a Phase III trial earlier this month.
A trial that would test Genasense in chemo-na ve CLL patients - randomizing them to get fludarabine plus South San Francisco-based Genentech Inc.'s Rituxan (rituximab), with or without Genasense - won a special protocol assessment in October. "The question is, would [Genta] want to do that one, or another sort of trial," Benjamin said.
"There was quite a bit of deliberation over [the trial that was the subject of the new drug application for CLL], and they did meet the primary endpoint," he pointed out. Genasense, which inhibits production of Bcl-2, a protein made by cancer cells that is believed to block chemo-induced apoptosis, also has failed in a Phase III trial in multiple myeloma. (See BioWorld Today, Nov. 30, 2004.)
"To say [Genta] has had its ups and downs is a gross understatement," Benjamin told BioWorld Today, pointing out that the firm was worth $1 billion in the days before the FDA panel put the kibosh on Genasense for melanoma.
Phase III problems with the compound in CLL sent former partner Aventis SA - now part of the Paris-based Sanofi Aventis Group - packing two years ago, but Genta got more than $250 million from the 2002 deal (valued at up to $480 million) before it was over. (See BioWorld Today, April 30, 2002.)