Genta announces positive results with antisense oligonucleotides in preclinical animal models of cancer.
The company has received authorization to begin human clinical trials in drug resistant follicular lymphoma patients at the Royal Marsden, a premier cancer research hospital in the United Kingdom.
The BCL-2 gene is over-expressed in many tumors. For example, 100 percent of follicular lymphomas, 92 percent of colon cancers and 70 percent of breast cancers over-express BCL-2. Over-expression of this gene may prevent normal programmed cell death or apoptosis. This is one of the new theories of how cancer cells gain a growth advantage over normal cells as the BCL-2 gene appears to postpone the death of cancer cells. The gene product of BCL-2 makes tumors resistant to a wide variety of chemotherapeutic agents as well as radiation.
Genta has been working in this field for four years and owns the antisense and gene therapy rights to the BCL-2 gene.
Two animal studies demonstrated the potentially significant anticancer effects of antisense. In one randomized, controlled study, nude mice transplanted with human colon carcinoma tissue were treated for two weeks with antisense therapy and a control sequence (i.e., a sequence not expected to have an effect). Animals treated with antisense therapy exhibited no tumor growth during the two-week treatment period and exhibited no growth for a brief period following cessation of antisense therapy. Animals treated with a control sequence exhibited tumor growth during and after the two-week treatment period.
In another animal model developed by Dr. Finbarr Cotter of the University of London, severe combined immune deficiency (SCID) mice (i.e., mice without immune response mechanisms) were injected with cells known to induce human follicular lymphoma. All mice developed lymphoma within 28 days. Certain of these mice then received 21 days of treatment with antisense therapy and became disease free. Animals examined 30 days following cessation of antisense treatment remained free of disease. There appears to be a strong relationship between treatment effect and the dose, duration and route of administration of antisense therapy. No toxicity was observed. In contrast, all animals treated with control sequences continued to exhibit disease.
Genta expects to initiate a human study mid-year following the completion of a standard toxicology study. This phase I/II trial will be conducted by Drs. Cotter and David Cunningham under physician INDs at the Royal Marsden.
"These results provide a solid foundation for the further development of Genta's Anticode program in cancer," said Thomas H. Adams, Ph.D., Genta's chairman and chief executive officer. "To our knowledge, no other antisense company working in this field has produced such results."
In 1993, there were an estimated 1.17 million new cancer cases and 526,000 cancer-related deaths in the United States. As the general population grows and ages, the incidence and prevalence of cancer are rising. By the year 2000, cancer is expected to replace heart disease as the number one cause of death in the U.S.
Genta Incorporated is an integrated biopharmaceutical company with a diversified product development pipeline. Genta's research focuses on the development of proprietary Anticode technology intended to block or regulate diseases at their genetic source. The near-term segment of the pipeline includes GEOMATRIX oral controlled-released drugs being developed by Genta Jago Technologies B.V., the joint venture between Genta and Jagotec AG, and novel topical dermatological products in various stages of clinical trials.
CONTACT: Genta Incorporated, San Diego
Thomas H. Adams, 619/455-2700
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|Date:||Feb 9, 1995|
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