Biopharmaceutical company Genta Inc. (GNTA.OB) has been waiting for too long to get FDA clearance for its controversial antisense cancer drug Genasense. On December 3, the FDA is expected to decide whether Genasense injection merits approval for Chronic Lymphocytic Leukemia.

Genasense, known generically as Oblimersen Sodium, is an antisense drug, which works by blocking a protein called Bcl-2, making cancer cells more vulnerable to death. Bcl-2 is one of the proteins produced by cancer cells that prevents cancer cells from dying. Blocking Bcl-2, therefore, may enable cancer treatments to be more effective.

In December 2003, Genta sought approval from the FDA for Genasense in the treatment of advanced melanoma, the most deadly form of skin cancer based on results from one of its Phase III clinical trials. The trial enrolled 771 patients with advanced melanoma who had not previously received chemotherapy. The patients were randomized to receive Genasense plus Dacarbazine, or Dacarbazine alone. The primary endpoint of the trial was to compare the overall survival between the two treatment arms.

According to the trial results, Bayer's Dacarbazine, which is commonly used in the treatment of advanced melanoma, when combined with Genasense delayed the median time before the disease worsened to 74 days from 49 days, reflecting a 51% improvement. Dacarbazine when combined with Genasense also resulted in an improvement in durable response rate of 6 months and a 72% increase in overall anti-tumor response rate.

However, Genasense failed to produce any improvement in overall survival rate and the FDA's Oncologic Drugs Advisory Committee declined to support the approval of the drug.

On April 30, 2004, the staff of the ODAC (Oncologic Drugs Advisory Committee) of the FDA stated in briefing materials in advance of the May 3, 2004 ODAC meeting that the Phase 3 clinical trial of Genasense failed to demonstrate a survival benefit, which was the primary trial endpoint. As a result of the announcement, the stock dropped $5.83 or 40.4% to close at $8.60 on an unusually high volume of over 30 million shares traded.

On May 3, 2004, the FDA panel voted 13-3, recommending the FDA to reject Genasense as the trials did not achieve the primary goal of prolonging lives. Following the news, Genta shares fell more than $3 per share to close at $5.11 that day.

On May 13, 2004 Genta withdrew its new drug application with the FDA for Genasense in the treatment of advanced melanoma.

The advisory committee's move dealt a blow to Genta's stock price and by the end of May 2004, the stock had fallen to $2.30, which reflected a decline of 81% since the start of 2004.

Then came yet another bad news, which sent Genta's stock price into a tailspin. Pharmaceutical giant Aventis, which had a collaboration agreement with Genta, since 2002, to develop and commercialize Genasense, bailed out of the partnership in November 2004. (Aventis merged with Sanofi to form Sanofi-Aventis in August 2004). Genta's stock price, which had already been on the wane, deteriorated further settling around $1.30, following Aventis terminating its partnership with Genta.

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