Even though OncoGenex Pharmaceuticals (NASDAQ:OGXI) and its pivotal programs with lead oncology candidate, custirsen, are being closely followed, investors are beginning to notice the company’s second generation antisense drug, OGX-427.
“We have data in bladder and prostate cancer with OGX-427 that, we believe, indicates clinical activity,” co-founder, president and CEO, Scott Cormack, says in an interview with BioTuesdays.com. “This has engaged our interest, even more so than at the beginning of the program. As a result, we have diversified our clinical program to go into other indications in order to explore the potential of the drug.”
He points out, “Quite a few investors have come into the story, not only because of custirsen, but also with a keen interest in OGX-427.”
Mr. Cormack explains that custirsen is designed to block the production of clusterin, a cell-survival protein that is over-produced in several malignancies and in response to many cancer treatments. Clusterin expression can be associated with treatment resistance and has been linked to faster rates of cancer progression and shorter survival.
At the end of 2009, OncoGenex partnered the development of custirsen with Teva Pharmaceutical Industries in a $430-million deal, with $60-million in upfront payments. Mr. Cormack says that none of the $370-million in additional milestone payments has been paid out yet. OncoGenex met its obligation to contribute $30-million toward the development of the drug in 2012, with Teva now funding all future development expenses. The deal also gives OncoGenex tiered royalties in the mid-teens to mid-twenties percent on future sales of custirsen.
OncoGenex and Teva are testing custirsen in two Phase 3 trials in advanced prostate cancer, called SYNERGY and AFFINITY, and in a third pivotal trial, called ENSPIRIT, for lung cancer.
Enrollment in the 1,000-patient SYNERGY trial, where custirsen is being studied in combination with first-line chemotherapy, concluded last November. The survival primary endpoint data are event-driven. The number of events required for final survival analysis is expected in the fourth quarter of 2013, with survival data expected to be released in the first half of 2014.
Mr. Cormack says that the FDA has indicated that it would accept a marketing application supported by the Phase 3 results of SYNERGY alone, since a similar randomized Phase 2 trial in prostate cancer would also be a supportive study for filing.
In a research report earlier this month, Leerink Swann analyst, Howard Liang, wrote, “…any Phase 3 outcome even approaching the Phase 2 results could validate both the target and the drug.”
In a Phase 2 study, the treatment benefit derived from the addition of custirsen on top of docetaxel and prednisone yielded a 6.9-month survival advantage, compared with the outcome of patients who received only the chemotherapy.
“With existing Phase 2 clinical data for custirsen showing activity in other large tumor settings, including breast cancer and non-small cell lung cancer, positive SYNERGY data could unlock meaningful value for the program by providing multiple shots on goal as well potential broad commercial opportunities,” Mr. Liang added.
In the AFFINITY trial, which began last August, custirsen is being combined with second-line chemotherapy in advanced prostate cancer patients who previously had been treated with docetaxel. The primary endpoint in the 630-patient study is overall survival.
Mr. Cormack says the ENSPIRIT trial, which began in September, is enrolling about 1,100 advanced or metastatic lung cancer patients who have progressed after first-line chemotherapy treatment has failed. One study arm is being treated with custirsen and docetaxel, while patients in the other arm receive docetaxel.
At the end of 2012, OncoGenex had $75-million in cash, which will take the company into 2015, well past the final data release in the SYNERGY trial.
Beyond custirsen, OncoGenex also is advancing its proprietary OGX-427 drug candidate in multiple ongoing and planned Phase 2 studies for the treatment of prostate, bladder, lung and pancreas cancer.
“OncoGenex continues to drive clinical programs for both OGX-011 [custirsen] and OGX-427 in what is among the most robust clinical pipelines in our coverage universe,” Byron Capital Markets analyst, Doug Loe, said in a research report earlier this month.
Mr. Cormack says the company presented data at ASCO last year from a Phase 1 study of OGX-427 in superficial or muscle-invasive bladder cancer. “The drug was infused into the bladder of patients who had surgery a week later to evaluate the action of the drug on the knockdown of heat shock protein 27 (Hsp27). Investigators found that one-third of patients had pathologic complete response or no tumor left even by microscopic evaluation. That’s one of the reasons that we’ve invested more heavily in pursuing the bladder cancer indication.”
Hsp27 is a cell-survival protein found at elevated levels in many human cancers. The development program for OGX-427 aims to demonstrate that inhibition of Hsp27 can lead to improved prognosis and treatment outcomes for cancer patients.
Mr. Cormack explains that the clusterin and Hsp27 programs have the same objectives but with different mechanisms of action. “OGX-427, on its own, has shown biologic activity while custirsen needs to be combined with a companion therapy.”
The company is currently studying OGX-427 in a Phase 2 trial in first-line metastatic bladder cancer that Mr. Cormack says is the primary registration path for the drug. Borealis-1 is a study of about 180 metastatic bladder cancer patients who have not received chemotherapy and are not candidates for surgery or radiotherapy. The primary endpoint of overall survival is expected to be reached in the fourth quarter of 2014.
“Survival is a highly unusual endpoint in a Phase 2 study,” he points out. “We want to have a read on survival in order to plan for a Phase 3 clinical trial in the future. Plus, Borealis-1 may also be used as a supportive trial so that we may only need to do one Phase 3 trial, instead of two, for initial FDA submission. On the other hand, because it is designed as a pivotal Phase 2 trial, if we achieve statistical significance for a survival benefit, we might be able to submit the data for registration.”
Last month, OncoGenex announced Borealis-2, a second-line metastatic bladder cancer study, with about 200 patients who have disease progression following initial platinum-based chemotherapy and are now being treated with docetaxel. The primary endpoint is overall survival.
Mr. Cormack notes that bladder cancer represents a major unmet medical need. “Nothing has been done for these patients for decades. Bladder cancer is difficult to treat and is underserved in terms of new therapies. So, we get pretty excited about the opportunity for OGX-427 as a potential treatment for patients with advanced bladder cancer. Plus, there is only one big clinical trial now underway in bladder cancer, so the ability to access patients is very good.”
In advanced prostate cancer, positive data from an earlier Phase 2 study of OGX-427 in patients with prostate cancer who had not previously been treated with chemotherapy led OncoGenex to begin another Phase 2 study in the fourth quarter, called the Pacific trial, in advanced prostate cancer patients who have rising PSA while receiving Johnson & Johnson’s Zytiga drug. The Pacific trial will study subsequent PSA, radiographic or symptomatic disease progression in patients receiving OGX-427 plus Zytiga against those remaining on Zytiga alone.
Mr. Cormack says the company also has under consideration potential Phase 2 trials with OGX-427 in metastatic lung cancer and metastatic pancreas cancer.
“We’re keeping Big Pharma and Big Biotech actively engaged on the OGX-427 program and sharing results with potential partners,” he adds. “But we’ll probably finish some of the Phase 2 studies before partnering, because additional data will likely derive greater value in a partnership deal, especially if we’re showing a survival benefit.”