Onyx Presents Data Supporting Therapeutic Virus Pipeline
RICHMOND, Calif., April 9 /PRNewswire-FirstCall/ -- Onyx Pharmaceuticals, Inc. (Nasdaq: ONXX - news) announced today that preclinical and clinical data supporting the use of Onyx's therapeutic viruses as a promising treatment for cancer were presented this week at the 93rd Annual American Association for Cancer Research (AACR) meeting in San Francisco, California. Researchers presented data based on seven abstracts covering Onyx's novel therapeutic virus products, including ONYX-015 clinical data in patients with sarcoma and patients with liver metastases of colorectal cancer.
In addition, Onyx announced that Frank McCormick, Ph.D., F.R.S., its founder and the Director of the University of California San Francisco (UCSF) Comprehensive Cancer Center and Cancer Research Institute, was awarded the prestigious American Association for Cancer Research 42nd G. H. A. Clowes Memorial Award. Dr. McCormick's Award Lecture, ``Cancer Therapy Based on Ras, RB, and p53'' was presented at the AACR in San Francisco on Sunday, April 7, 2002.
Researchers at Onyx presented promising data on one of its cytosine deaminase (CD) Armed Therapeutic Virus(TM) (ATV) product candidates. CD is an enzyme that converts an inactive prodrug, 5-fluorocytosine (5-FC), into its highly cytotoxic form, 5-fluorourocil (5-FU), a commonly used first-line chemotherapuetic agent. ATV is a proprietary technology in which therapeutic genes such as the CD gene are placed strategically into Onyx viruses such that expression occurs as a condition of virus replication preferentially within cancer cells. Data presented describes the ONYX-411 virus with selectivity for cancer cells defective in the Retinoblastoma (RB) pathway, and demonstrates its use for highly selective expression of CD in tumor cells. Onyx believes that these results suggest therapeutic viruses armed with a prodrug-activating enzyme represent promising anticancer therapeutics with increased efficacy over virus alone.
``We expect a CD Armed Therapeutic Virus to be one of our next virus candidates for clinical development,'' said Leonard Post, Ph.D., Senior Vice President of Research and Development at Onyx. ``We believe the data suggest that the tumor-selective replication of the Onyx viruses can be used for delivery of genes that enhance the therapeutic effect over unarmed virus.''
Onyx researchers also presented data demonstrating that its therapeutic viruses can be armed with other anticancer genes such as the Tumor Necrosis Factor alpha (TNF alpha) gene to control TNF alpha expression levels specifically at the tumor site. Clinical results have demonstrated that TNF alpha directly delivered to tumors can lead to antitumor response without toxic side effect to surrounding healthy tissue. However, due to dose- limiting systemic toxicities, Onyx believes that therapy to treat widely disseminated tumors by intravenous administration of TNF alpha is not possible. Onyx's virus armed with TNF alpha restricted the TNF alpha expression to the tumor environment by expressing the gene when the virus replicates. In contrast, the plasma levels of TNF alpha were substantially lower than the tumor levels. These results suggest the possibility that TNF alpha can be delivered to tumors using Onyx viruses resulting in a minimum level of systemic toxcities.
In addition, Onyx scientists presented the company's unique bioselection technology, a tool to isolate novel therapeutic viruses with enhanced selectivity and potency. Using the bioselection process, Onyx was able to identify viruses that selectively replicate up to 1,000-fold more efficiently than ONYX-015. These viruses may provide significantly enhanced antitumor activity in human cancers.
The presented results of research on the coxackievirus and adenovirus receptor (CAR) suggest that repeat administration of adenoviruses could lead to further antitumor effects. Onyx scientists investigated the role of CAR in determining replication and spread of adenoviral therapy such as ONYX-015 and ONYX-411. It was observed in human xenograft models of cervical cancer that adenovirus treatment did not select for cells lacking the receptor in this system.
Finally, researchers at the Mayo Clinic, Cornell University and Stanford University presented updates on the Phase I/II and Phase II ONYX-015 data in chemotherapy-naive patients with sarcoma, ONYX-015 replication and spread data in a patient with primary gall bladder carcinoma and patients with liver metastases of colorectal cancer, respectively. In the ongoing dose-escalating Phase I/II study of ONYX-015 in combination with chemotherapy regimens of mitomycin-C, doxorubicin and cisplatin (MAP), four patients have been treated to date with ONYX-015 administered via intratumoral injections. No serious toxicities related to ONYX-015 have been documented thus far, and ongoing accrual at the highest dose level will allow for a future assessment of efficacy. Immunohistochemistry of the metastatic lesions prior to treatment showed that three of the four patients had mutant p53. Viral DNA was detected in two of the four patient biopsies on day five of the first cycle and ONYX-015 viral genome was detected in the peripheral blood in three of the four patients on day five of the first cycle suggesting viral replication. Sarcomas are tumors of the connective tissues, and approximately 40 to 75 percent of sarcomas contain p53 functional mutations. The study is ongoing, and efficacy will be assessed at the highest dose levels.
Investigators from Cornell University reported data on ONYX-015 life cycle and mechanism of action collected from a patient with primary gall bladder cancer. In the course of a clinical trial, the patient was injected with ONYX-015. Based on the biopsies, ONYX-015 was detected at 24 hours and 7 days following injection of the virus, confirming that ONYX-015 is capable of replicating in tumor cells up to one week after injection.
Further data analysis of the completed Phase I/II study of ONYX-015 in patients with colorectal carcinoma metastatic to the liver were presented. The safety and efficacy results from 33 patients have been reported to date. The investigators presented at this meeting, an updated analysis of expression of various cytokine levels and viral genome levels. The presentation also highlighted results from two patients. One patient who had progressed on standard chemotherapy demonstrated a marked reduction in Carcinoembryonic Antigen (CEA), a tumor marker for colorectal cancer, when given ONYX-015 plus chemotherapy. Another patient who had been heavily pretreated with standard chemotherapy demonstrated viral genome and cytokine levels that suggested virus replication even after repeated doses of ONYX-015. These data warrant additional clinical study of ONYX-015 in this indication.
Onyx Pharmaceuticals is engaged in the discovery and development of novel cancer therapies. Based on its proprietary technologies that target the molecular basis of cancer, the company is developing its lead products, ONYX-015 and BAY 43-9006. For more information about the company's pipeline and activities, visit Onyx's website at www.onyx-pharm.com.
This press release contains certain forward-looking statements regarding the development of potential human therapeutic products that involve a number of risks and uncertainties. Actual events may differ from the company's expectations. In addition to the matters described in this press release, the timeline for clinical activity, results of pending or future clinical trials, and changes in the status of the company's collaborative relationships, as well as the risk factors listed from time to time in the company's periodic reports filed with the Securities and Exchange Commission, including but not limited to its Annual Report on Form 10-K, may affect the actual results achieved by the company.
SOURCE: Onyx Pharmaceuticals, Inc. |
