West Coast Editor
Genta Inc.'s ongoing bid to find a replacement partner for Genasense can only be helped by more positive news from its Phase III study testing the compound with chemotherapy against relapsed or refractory chronic lymphocytic leukemia.
Wall Street liked the news enough to boost the company's stock (NASDAQ:GNTA) by 44.5 percent. Shares closed Monday at $1.85, up 57 cents.
"People are pretty enthusiastic, at least today," said Reni Benjamin, analyst with Rodman & Renshaw in New York. "We have a market perform' [rating] on the stock, and based on this data, we're reassessing the potential," with a poll of hematologic physicians in the works.
Genta lost its partner, Aventis SA (now the Paris-based Sanofi-Aventis Group), after reporting mixed data last year from the CLL study, but further analysis turned up a significant increase in major response, the trial's primary endpoint. (See BioWorld Today, Dec. 7, 2004.)
Now, at meetings in New York of the International World Congress on CLL and also at the First Annual Meeting of the Oligonucleotide Therapeutic Society, Genta said the latest data show the antisense compound gained for patients a significantly longer remission duration and significantly lower risk of relapse.
With a new drug application pending at the FDA for accelerated clearance, Genta is asking for a meeting with the agency to talk about a post-approval confirmatory trial.
Specifically, the Phase III study enrolled 241 patients and randomly assigned them to get fludarabine plus cyclophosphamide chemotherapy with or without Genasense.
The trial nailed its primary endpoint, a statistically significant increase in the proportion of patients who gained a complete or nodular partial response (CR/nPR). Those totaled 17 percent, as compared to the non-Genasense group's 7 percent (p=0.025).
So far, six of the eight patients who achieved CR/nPR with chemotherapy alone have relapsed, compared with five of 20 Genasense patients. The median duration of CR/nPR was 22 months in the chemotherapy-alone group, and has not been reached in the Genasense group (p=0.03).
All CR/nPR responses have lasted longer than six months.
"The durability looks fairly long, but there are quite a few things we have to get our hands around - mainly the safety issue," Benjamin said.
Genta reported that Grade 3 or Grade 4 adverse events in the Genasense group included, but were not limited to, thrombocytopenia, nausea, and catheter complications - problems that caused therapy to stop in an equal percentage of patients in both groups.
More troubling, nine patients in the Genasense group and five patients in the chemotherapy-alone group had adverse events that resulted in death, including two Genasense patients who died from complications associated with tumor lysis and cytokine release syndrome.
"This is a very sick population, but the fact that there were twice as many deaths in the Genasense arm will make you think," Benjamin said, pointing out that the issue was "one of the things that came up at ODAC with the melanoma application."
In May 2004, the agency's Oncologic Drugs Advisory Committee gave Genasense a thumbs down for advanced melanoma, and the company reduced its work force by half to conserve cash. (See BioWorld Today, May 4, 2004.)
Genta hasn't given up on antisense, and Benjamin said the firm "may be one of the last ones to go forward with the first generation of antisense molecules. With the amount of time and money it's going to take for them to come up with a new formulation, you might as well take your chances with the FDA, especially with a population [such as patients with CLL] that has no therapeutic options."
And the data do keep improving. Did Aventis make a mistake by walking away too soon?
"Aventis was going through quite a few things at the time," Benjamin noted. "[Genta's] melanoma application had failed, the CLL trial was about to be unblinded, and most importantly, [Aventis] went through the Aventis-Sanofi merger. I don't think it was Aventis' decision - I think Sanofi came in and cleaned house. Did Sanofi make a mistake? Still too early to tell."
In August, Genta raised $17.5 million, and "several months before that, we helped them raise $20 million," Benjamin said. "They have enough cash to last them into a decision from the FDA. That will be probably by June of next year."
The happy reaction to the most recent news could help the company raise more money, so it doesn't have to "bet the farm" on the FDA decision while working to partner the drug.
Genasense also has been tried against advanced multiple myeloma but failed last year, sending Genta's stock down 23 percent to $1.27 and causing at least one analyst, Kate Winkler, vice president of equity research for Merriman Curhan Ford & Co. in San Francisco, to predict the firm was in major trouble. Winkler is no longer with Merriman and could not be reached. (See BioWorld Today, Nov. 30, 2004.)
"I wouldn't count them out just yet," Benjamin said.
Separately, Berkeley Heights, N.J.-based Genta's board adopted a stockholder rights plan that the company said is designed to enhance the ability to protect shareholders against, among other things, unsolicited takeover attempts that do not offer an adequate price or otherwise are not in their best interests. The plan did not come in response to any specific effort, officials noted.