Partners target ovarian cancer
TORONTO—Targeted toward developing a more personalized—and more effective —therapy for cancer patients, Canadian company Axela and Irvine, Calif.-based OvaGene Oncology have agreed to a molecular diagnostics partnership aimed at developing and marketing a test to discover the best weapon to kill ovarian cancer, one of the deadliest forms of cancer.
Axela's Ziplex platform is optimized to perform complex gene and protein expression assays in a distributed testing environment, and is designed for customized applications in RNA and protein research, according to a company press release.
By partnering with OvaGene for proprietary content, Axela creates an opportunity to make such tests available on a global basis.
In the United States alone, 182,000 women are currently living with a confirmed diagnosis of ovarian cancer, OvaGene reports. Approximately 145,000 of those patients will receive chemotherapy and could potentially benefit from the diagnostics test. The U.S. National Institute of Health (NIH) reports that 1 million American women have a confirmed diagnosis of a gynecologic cancer, 587,000 have endometrial cancer and 250,000 have cervical cancer.
OvaGene, with its particular expertise within the field of gynecologic cancers and through its CLIA Laboratory, is focused on developing and commercializing proprietary gene-based signatures and assays to personalize the treatment of ovarian, uterine and cervical cancers.
The first of OvaGene's proprietary gene signatures was implemented on Axela's Ziplex platform beginning on Aug. 21. The signature will be made available to physicians to assist in personalizing the selection of drugs commonly used to treat recurrent ovarian cancer.
Michael Treble, executive chairman of Axela, says the partnership "is another important addition to Axela's pipeline of diagnostic content. OvaGene's unique signature directly complements our other development programs, including the breast cancer risk-of-recurrence assay."
"The relationship with Axela has the potential to rapidly yield significant benefits to patients and their physicians. In the U.S., over 20 drugs may be used to treat recurrent ovarian cancer, each showing a low 12- to 15-percent response rate," Frank J. Kiesner, founder and CEO of OvaGene, stated in a press release. "When available, OvaGene's proprietary gene signature will provide physicians an opportunity to improve these response rates by personalizing drug selection. Through this partnership with Axela and with access to their unique platform, we can rapidly offer the highest quality gene signature-based testing to gynecologic oncologists."
In utilizing the Flow-Thru Chip's versatility to perform both gene and protein analysis, Axela is well positioned to address the need for automated multiplex testing in a wide range of laboratory environments, he adds.
"The combination of OvaGene's validation expertise, Axela's distributed platform and complementary signature content led to creation of the partnership," says Paul Smith, chief operating officer of Axela.
The personalized selection of drugs is achieved through two components, Smith says. First, a gene signature is validated to accurately identify the pathways that are activated in a particular tumor sample in order to match those to the mechanism of specific drug therapies. The Ziplex platform then enables these tests to be carried out.
Dr. Jay Coonan, founder, director and executive vice president of OvaGene's strategy and business development, tells ddn, "the area of gynecologic cancers, including ovarian cancer, represents a huge unmet need in diagnostic tools to help the physician care for oncology patients. The addition of the OvaGene content (the initial assay to predict response to chemotherapy for ovarian cancer) to the Axela platform in this partnership will accelerate the distribution both locally and, with continued clinical validation, globally in a cost-efficient manner."
The statistics for ovarian cancer "are grim," Coonan says. "There are about 23,000 new cases per year, but about 15,000 deaths yearly. The vast majority of patients are diagnosed at an advanced stage (III/IV) due to the vagueness of the presenting symptoms, often causing missed or delayed diagnosis."
Plus, the diagnostic tools have been "woefully inadequate," Coonan says.
"There have been no dramatic therapeutic breakthroughs as yet, either," he notes. "Thus, about 75 percent of ovarian cancer patients die within five years of initial diagnosis. Unfortunately, 25 percent of those initially treated have either no response or an early recurrence within six months and are called 'platinum- resistant.' Those patients having a recurrence of cancer at 12 months or later after chemotherapy are classified as 'platinum-sensitive' and are generally retreated with a platinum drug. Sadly, eventually all patients become 'platinum-resistant.'"
Ovarian cancer, like all cancers, arises by mutations in the genes and DNA of the cells, he said. The Cancer Genome Atlas analysis of ovarian cancer showed 85 genes associated with improved survival and 108 genes associated with poor survival. The problem remains of how to apply this enormous amount of new information realistically in the clinic.
"It is a huge challenge in the condition of 'platinum resistance' to find another drug or drug combination to which the tumor might respond," Coonan says. "Currently, the selection of drug is based on the physician's experience, specific drug toxicities or randomly chosen from those drugs traditionally tried for the disease. That selection numbers almost 25 different drugs. Unfortunately, each drug generally has only a 10- to 15-percent response rate in this resistant/recurrence setting. The new hope of 'targeted therapies' (bevacizumab, Avastin) has led to some renewed optimism. However, even these drugs so far have generally poor response rates.
"The challenge going forward is to correlate these multiple genetic/DNA changes in the form of gene signatures, such as OvaGene and Axela are developing, with specific drugs to identify which tumors have a truly better chance of responding to a particular therapy," Coonan continues. "Tumors are 'smart' and mutate frequently to bypass the genetic pathway that a specific drug blocks, thus rendering the cancer again 'resistant.' Going forward, it becomes vital in drug selection for each individual patient to know what genetic pathways are active to match the therapy with a similar activity, thus giving the best chance of a good result."
OvaGene has a strong pipeline of proprietary molecular diagnostics that, with proper validation and appropriate approval on a multiplexing platform, could have a global effect on improving the care of women suffering from gynecologic cancers, Coonan says.
"Many of OvaGene's assays have the potential applicability to other tumor types as well. Together with Axela, this represents an extraordinary opportunity for both companies," he says.