Without the benefit of full data on a 771-patient Phase III trial, Wall Street remained a little wary about results released Wednesday by Genta Inc. and partner Aventis SA on Genasense, an antisense oncology compound being studied in malignant melanoma.
Nevertheless, Raymond Warrell, Genta's CEO, told BioWorld Today the companies initiated filing of a rolling new drug application, expected to be completed in mid-fourth quarter.
Warrell and his partners at Aventis, of Strasbourg, France, were excited that the randomized trial designed to compare Genasense plus dacarbazine with dacarbazine alone demonstrated a 25 percent improvement in patients who finished the minimum follow-up of 12 months (n=480). Specifically, the median treatment-arm survival rate was 10.1 months, compared with 8.1 months for dacarbazine alone (p=0.035).
Furthermore, analysis of all patients in the treatment arm showed a median survival of 9.1 months, compared with 7.9 months for patients on chemotherapy alone (p=0.184).
Genta's stock (NASDAQ:GNTA) closed Wednesday at $15.22, down 79 cents.
The primary endpoint was to compare the overall survival between the two treatment arms. Secondary endpoints included comparative analyses of progression-free survival and tumor responses.
"We have a [primary] endpoint that has not yet been reached because patients need about another 90 to 100 days of follow-up. However, if you look at the patients who have been followed for at least one year, you have a highly significant difference [in survival], and we are very confident that the final group of patients, as they begin follow-up for another three or four months, will in fact track the same way as the first group of patients," Warrell said. "The first group of patients are looking at about 25 percent improvement in overall survival, which is actually spectacular for patients with melanoma."
Indeed, in a research note released to BioWorld Today, Mark Monane, principal, equity research, with Needham & Co. in New York, said, "While the intent-to-treat survival analysis (primary outcome) with the entire cohort did not yet reach the p<0.05 criteria, we note that a large proportion of patients were enrolled in 2H02/1Q03. Therefore, we believe the intent-to-treat analysis (whole cohort) to improve as the patients are followed longer in the trial and potentially mirror the intent-to-treat data seen in patients enrolled before August 2002 (n=480)."
Warrell also pointed out that treated patients showed a significant increase in median progression-free survival to 78 days, compared with 49 days in the chemotherapy group (p=0.001). Patients in the treated group achieved an antitumor response rate of 11.7 percent, compared with 6.8 percent in the chemotherapy group (p=0.019).
"These are very exciting results. Melanoma is a disease for which there's a consensus that virtually nothing works. There's a crushing unmet medical need for these patients, and this is really the first drug in a quarter of a century to have such spectacular results," Warrell said. "I think the application here is going to be very strong. We are not going to delay completion of the NDA pending the collection of additional information. We've talked to the agency and we are planning to file on the information released today and add additional information after the NDA is complete."
The FDA has granted Genasense orphan and fast-track status in melanoma, myeloma and chronic lymphocytic leukemia (CLL). Phase III trials on the latter two diseases are fully enrolled.
Genta and Aventis (Genta's exclusive partner for Genasense) intend to seek priority review - or six-month review - for melanoma. Although Warrell would not commit to such a time frame, if the NDA is filed by the end of the year and awarded priority review, FDA action could occur in the summer of 2004.
Meanwhile, Warrell said Genta and Aventis plan to begin analyzing data on the myeloma trial, and subsequently the CLL trial, following completion of the melanoma NDA. The plan is to win approval on melanoma, and later file supplemental applications for myeloma and CLL.
Financially, Genasense, a candidate developed by Genta, has netted the Berkeley Heights, N.J.-based company a pretty penny. At the time of the signing, the deal between Aventis and Genta was valued at $480 million. So far, Warrell said, Genta has collected about $200 million, and would receive another $95 million on FDA approval of the first indication. (See BioWorld Today, April 30, 2002.)
The companies will co-promote Genasense in the U.S. Aventis owns the rights in other parts of the world.