Oncogenex Pharmaceuticals Inc. shares (Nasdaq:OGXI) fell 60.3 percent after the company and its partner, Teva Pharmaceutical Industries Ltd., reported that their experimental prostate cancer therapy, custirsen, failed to perform better than standard chemotherapy in a pivotal trial.

Scott Cormack, president and CEO of Bothell, Wash.-based Oncogenex, called the results surprising and just the opposite of the encouraging data produced by earlier trials. Oncogenex and Teva will now review the data, he told BioWorld Today, taking a closer look at how treatment with new therapies approved since the trial began, such as Zytiga (abiraterone, Johnson & Johnson) and Xtandi (enzalutamide, Medivation Inc. and Astellas Pharma Inc.), may have "shifted the landscape" and impacted its outcome.

"We are disappointed with these results," said Michael Hayden, Teva's president of global R&D and chief scientific officer. "Addressing treatment resistance is critical in the fight against cancer. We are working with Oncogenex to more fully understand these data."

Results in the study, called Synergy, showed that adding custirsen to standard chemotherapy with docetaxel and prednisone did not significantly improve overall survival for the 1,022 men with metastatic castrate-resistant prostate cancer enrolled in the trial. Men in the treatment arm had a median survival of 23.4 months, vs. 22.2 months in the control arm. The trial's hazard ratio, a measure of how patients in the treatment group fared vs. those receiving a placebo, showed very little difference between the two groups.

A phase I proof-of-concept study had shown custirsen capable of penetrating tumor cells, and targeting and suppressing clusterin, a protein that may play a fundamental role in cancer cell survival and treatment resistance. Later, a randomized phase II trial, similar in design and patient selection to Synergy, demonstrated an overall survival advantage for custirsen in combination with docetaxel.

Synergy's miss has left the company looking to its future for more hopeful data. Custirsen is still in phase III testing to treat prostate and non-small-cell lung cancer (NSCLC) in combination with second-line chemotherapies, areas in which Cormack said he sees promise and added that the company has adequate funding to evaluate. But investors showed more concerned with the short-term, sending Oncogenex shares plummeting to a new 52-week low of $3.82, and ending the day on Monday at $3.85, down $5.85.

It's the second time Oncogenex shares took a big hit over custirsen. Shares fell nearly 29 percent when Oncogenex first announced its partnership with Jerusalem-based Teva in December 2009, likely due to investor disappointment over deal terms that seemed less impressive than those for other late-stage prostate cancer drugs at the time. (See BioWorld Today, Dec. 22, 2009.)

Now, the company will need to work hard to bring spooked short-term investors around. "I think as people dive into this story more acutely, they'll find this is just one catalyst, but there's more potential shots on goal," Cormack said. "This is just one trial out of total of 10."

The company is now focused on Affinity, a phase III trial evaluate the survival benefit for custirsen in combination with Jevtana (cabazitaxel, Sanofi SA) treatment as second-line chemotherapy in patients with castrate-resistant metastatic prostate cancer, he said. It expects to complete enrollment by the end of 2014 and show data during the second half of 2015.

Because clusterin, the protein custirsen inhibits, is more heavily expressed as a reaction to treatment, Cormack expects the drug may provide increased benefit in more heavily treated patients, such as those in both the Affinity and NSCLC-focused Enspirit trials.

Oncogenex, which will report first-quarter 2014 results April 30, had $39.2 million in cash on hand at the end of 2013. Cormack said that will be enough to fund the company beyond the first quarter of 2015. That will allow it to complete and report data from its phase II trial of its unpartnered drug, apatorsen, in the Borealis 1 trial in advanced bladder cancer; complete patient enrollment in the Affinity trial; provide an interim futility analysis in the Enspirit trial; and complete enrollment for a phase II trial of apatorsen for the treatment of non-squamous NSCLC.

"We remain strong in our belief that targeting mechanisms of treatment resistance is a critical path forward in the fight against cancer, and we continue to actively pursue this approach," Cormack said, during a Monday investor call held to discuss the results.