Genta Inc. and partner Aventis SA said Genasense injection for use in combination with dacarbazine now is available through an expanded access program in the U.S. for patients with advanced melanoma who have not previously received chemotherapy.
Genasense (oblimersen sodium) in combination with dacarbazine (DTIC) as a treatment for advanced melanoma has been granted priority review by the FDA and is scheduled to be discussed by the Oncologic Drugs Advisory Committee May 3 in Gaithersburg, Md.
Genasense, an antisense cancer compound, targets the Bc1-2 protein to boost the effectiveness of chemotherapy. The candidate is the subject of about 20 trials in a variety of hematologic and solid-tumor types, Joy Schmitt, spokeswoman for Genta, of Berkeley Heights, N.J., told BioWorld Today.
The firm completed the rolling new drug application for Genasense in late December. Under guidelines established in the Prescription Drug User Fee Act III (PDUFA III), the FDA is compelled to take action on the application on or before June 8.
Meanwhile, Genasense in combination with DTIC will be available at certain clinical sites throughout the country for eligible patients with Stage IV and unresectable Stage III melanoma who have not been previously treated with dacarbazine or temozolomide-containing chemotherapy regimens. Expanded access programs are designed to make investigational agents available at the earliest opportunity for the treatment of patients with diseases for which no comparable or satisfactory alternative drug is available.
DTIC, which has been on the market since 1975, and interleukin-2 are the only treatment options available for patients with advanced melanoma.
The Genasense NDA is based on a 771-patient Phase III trial that missed the survival (primary) endpoint, but revealed a positive trend, Schmitt said. Participants, all of whom were chemotherapy na ve, were randomized to receive Genasense plus dacarbazine or dacarbazine alone. (See BioWorld Today, Sept. 11, 2003.)
Schmitt said the data showed a 25 percent improvement rate in treated 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). 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 and Aventis hope the FDA will grant approval based on favorable secondary endpoints including tumor response and progression-free survival. Specifically, 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). Meanwhile, treated patients showed a significant increase in median progression-free survival to 74 days vs. 49 days in the chemotherapy group (p=0.001).
Adverse events included fever, neutropenia, thrombocytopenia, leukopenia, anemia and nausea.
Beyond advanced melanoma, the partners have completed enrollment of a 241-patient Phase III trial in chronic lymphocytic leukemia and a 220-pateint Phase III trial in multiple myeloma. The firms have not said which indication will be filed following a decision on advanced melanoma.
Aventis, of Strasbourg, France, signed on as Genta's partner in the development of Genasense two years ago in a deal valued at $480 million. So far, Genta has collected about $250 million and is poised for another milestone on approval of the candidate in 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.
Genta won its first drug approval in September: Ganite (gallium nitrate injection) for the treatment of cancer-related hypercalcemia that is resistant to hydration. (See BioWorld Today, Sept. 19, 2003.)
Genta's stock (NASDAQ:GNTA) closed Tuesday at $12.82, up 52 cents.