“Murky” data leave doubts over Genta, Aventis antisense cancer drug

Genta Inc. and Aventis SA said on Wednesday they were seeking approval for new skin cancer drug Genasense, even though it showed only limited results in a late-stage clinical trial.

Genasense is a new type of drug that makes use of antisense technology. It works by reducing production of Bcl-2 protein in cancer cells that is believed to be a fundamental cause of resistance to standard anticancer therapy. There has been considerable scepticism about the approach and investors have been keenly awaiting results from the pivotal phase III trials, involving 771 patients. Genta Chief Executive Ray Warrell said the drug could be approved early next year, now that Genta and Aventis have filed the first portion of their new drug application to the U.S. Food and Drug Administration (FDA). But Qynh Pham, a biotech analyst for Delafield Hambrecht Inc., said the trial data were “murky and incomplete” because 35% of enrolled patients with malignant melanoma had not yet completed 12 months of treatment. “I’m mildly pleased with the results, but we don’t have a full set of data. So it’s hard to interpret the results at this point,” she said. The trials showed that patients given Genasense in combination with dacarbazine, a standard chemotherapy drug, had a median survival time of 9.1 months against 7.9 months for patients treated with dacarbazine alone. That was an improvement of 15%, but was short of the 20% the study had aimed for. Patients who completed a minimum follow-up time of 12 months, meanwhile, had a median survival of 10.1 months, compared with 8.1 months – a 25% improvement. “I think they should hit a 20% improvement in overall survival over time but the FDA may want to see the additional data before they are confident with that outlook,” said Mark Purcell, industry analyst with Deutsche Bank. Genta and Aventis have also conducted final phase III studies in multiple myeloma, or bone marrow cancer, and chronic lymphocytic leukemia. Trials in other cancer types are further behind. Genasense is also being investigated for use in blood, colon, breast, lung, lymph and prostate cancer. Franco-German drugmaker Aventis agreed last year to pay $480 million for rights to Genasense. Aventis will market the drug outside the United States, where the two companies will share marketing. (Source: Ransdell Pierson and Ben Hirschler: Reuters Health: September 10, 2003: Oncolink)