SAN DIEGO -- Genta ( GNTA) may seek a second shot at marketingapproval for its experimental cancer drug Genasense, but don't expectthings to turn out any better than the first time. Still, some investors seemed eager to take a flier on Genta'schances at resurrection. The stock closed up 67 cents, or 48%, to$2.05 on Monday. But that was down from its intraday high of $2.40, or up 74%, reached before a presentation on a form of leukemia at 2:15 p.m. EDT. More than 62 million shares traded hands in a company with a 73 million-share float and a 30-day daily average volume of 2.9 million shares. At an oral presentation at the American Society of Hematologymeeting Monday, the Berkeley Heights, N.J.-based drugmaker said theaddition of Genasense to chemotherapy increased "major" responses inpatients with advanced chronic lymphocytic leukemia (CLL) in a phaseIII study. But this increase in response had no clinically meaningful effecton patients in terms of increasing their survival or even delaying theprogression of disease. And the Genasense-chemotherapy combinationused in the study is relatively outdated, with newer drugs, including Genentech's ( DNA) Rituxan, producing better responses in similar CLL patients. During Monday's presentation, the Genasense study's leadinvestigator, Dr. Kanti Rai of Long Island Jewish Medical Center, didnot specifically endorse a Food and Drug Administration filing based on this clinical data. While he believes in the promise of Genasense in CLL, Rai said different dosing schedules and/or studies of the drug in newlydiagnosed (read: less sick) CLL patients is needed. Genta has not yet said publicly whether it will seek FDA approvalfor Genasense in CLL, but the down-and-out company has little to lose.In May, Genasense was rejected by an FDA advisory panel as a melanomatreatment, sending shares tumbling into the single digits. At present,Genta has lost its corporate partner, Aventis ( AVE), and is running short of cash. A separate phase III study in multiplemyeloma, also presented over the weekend at the ASH meeting, was afailure.
The phase III study enrolled 120 patients who were given a combination of Genasense plus chemotherapy; another 121 patients weregiven chemotherapy alone. All patients in the study were diagnosedwith advanced CLL, which means they had received, and failed, priortherapies. Nineteen patients, or 16%, in the Genasense arm of the studyachieved a major response -- defined as a complete response orso-called nodular partial response, compared to with eight patients, or 7%, inthe control arm. This result, the study's primary endpoint, wasstatistically significant, albeit not robustly so with a so-called p value of0.039.
A p value of 0.05 is required for a study to reach statisticalsignificance, but strong data typically have a p value of less than0.01. But a more conventional primary endpoint in CLL studies looks atoverall response rate, defined as a complete response, nodular partialresponses and partial response. When the Genasense data were analyzedthis way, overall response in the Genasense arm was 41%, less than the45% overall response rate in the control arm. Also, patients in the Genasense arm of the study progressed (theirdisease worsened) at a median time of 6.1 months, faster than the8.9 months for patients in the control arm. Overall survival data were not analyzed, pending further maturing of the data. Despite a series of setbacks this year that have left Gentareeling, the company seems intent to push ahead with Genasense'sdevelopment. No doubt, persistence sometimes pays off. But for Genta,the second time will not likely be the charm.