FDA NOT CONVINCED OF EFFICACY OF TWO POTENTIAL ONCOLOGY DRUGS; GENTA, ALLOS SHARES FALL
May 3, 2004
Faxwatch © 2004
Shares of Genta Inc. plummeted 40.4 percent and shares of Allos Therapeutics Inc. tumbled 45 percent after documents posted on the Food and Drug Administration’s Web site showed that regulatory reviewers are not convinced either of the firms’ investigational oncology drugs are effective.
The documents were released in advance of a meeting of the FDA’s Oncologic Drugs Advisory Committee scheduled for May 3 and 4. The committee will discuss Genta and Aventis SA’s Genasense (oblimersen sodium) for use in combination with dacarbazine for treating advanced melanoma. They will also discuss Allos Therapeutic’s RSR13 (efaproxiral sodium) injection for use as an adjunct to whole brain radiation therapy in treating brain metastases from primary breast cancer.
Genta has submitted Phase III trial results to the FDA, during which, 771 patients received Genasense plus dacarbazine or dacarbazine alone every three weeks as first-line chemotherapy for metastatic melanoma. The primary endpoint was overall survival.
While patients who received the combination had significantly longer progression-free survival and a higher response rate, the results failed to show a survival benefit versus dacarbazine alone.
Furthermore, toxicity was higher in the combination arm, and the reviewers pointed out other issues with the secondary endpoint results.
“Any claims of improved efficacy based on secondary endpoints, progression-free survival and anti-tumor response rate are questionable because of the open-label nature of study, missing data and differences in assessment interval between the two treatment groups,” they said. “The findings could be falsely positive, especially in view of the lack of confirmation by a second well-controlled and well-conducted trial.”
Similarly, another reviewer found that “the evidence submitted in [Allos’] application ... is not convincing and does not support the sponsor’s claim of efficacy.”
Allos had submitted data from a Phase III trial in which 538 patients received whole brain radiation therapy for brain metastases plus supplemental oxygen with or without RSR 13.
Results showed no statistically significant difference in survival between the two study arms in the intent-to-treat population.
However, the median survival time for a subset of patients with breast cancer was 4.57 months in the control arm versus 8.67 months in the treatment arm. But subgroup findings are only considered exploratory or hypothesis-generating analyses, the document said.
“It is not evident that the apparent survival advantage observed in a single small subgroup of patients with primary breast cancer based on post-hoc analyses is attributable solely to the treatment effect and not due to imbalances in known and unknown prognostic factors,” a reviewer concluded.
Shares of Genta closed at $8.60, down $5.83, while shares of Allos closed at $2.55, down $2.09, both in heavy trading on the Nasdaq. |
