Ten years after starting the first human trials of its lead anticancer drug Genasense (oblimersen sodium injection), Genta (www.genta.com) is seeking marketing approval for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) when Genasense is given in combination with fludarabine and cyclophosphamide. In late December, the company filed an NDA for Genasense, a pro-apoptotic drug.
The NDA, which already has both orphan drug and fast track designation, was accepted for review by the FDA and has been granted an action date in October 2006.
In January, Genta also submitted a marketing authorization application (MAA) to the European Medicines Agency for the approval of Genasense in combination with dacarbazine for the treatment of advanced malignant melanoma. “Genasense is a breakthrough drug for oncology, and we look forward to getting the drug into the hands of physicians and patients as soon as possible,“ says oncologist Raymond P. Warrell, Jr., M.D., the company’s CEO.
Furthermore, the approval of Genasense would give economic validity to the entire therapeutic platform of drugs based on RNA and DNA technology. “The scientific validity of the platform has been there for a long time,“ says Dr. Warrell, but “economic validation is still missing.“
Based in Berkeley Heights, New Jersey, Genta was founded in San Diego in 1988 as a spinoff of GenProbe (www.genprobe.com to discover therapeutics based on the then new antisense technology. Genasense began clinical testing in 1995. Dr. Warrell joined Genta in late 1999 to guide the company’s development of therapies for cancer, based on proprietary antisense and small molecule technologies.
This is Genta’s second attempt to obtain FDA approval for Genasense in the U.S. The company withdrew a previous NDA for malignant melanoma in mid-2004 when the FDA’s oncology drug advisory committee voted not to recommend it.
Since then, Genta scientists have completed long-term follow-up of patients enrolled in the this trial which is the basis of the current MAA in Europe. Long-term follow-up suggest that “the maximum benefits of Genasense become apparent later rather than earlier,“ says Dr. Warrell.
When the melanoma NDA was submitted in 2004, patients had been followed for a minimum of only seven months, and the long-term outcomes were not apparent. Recent data reveal that Genasense works best when given to patients before other drugs supervene and trigger mechanisms of drug resistance. Moreover, in the current NDA being reviewed by FDA, complete or partial remissions that occur in Genasense patients are maintained for up to 24 months, according to Dr. Warrell, whereas patients not given Genasense relapse significantly sooner.