to work differently than all the others made by the competition, as it is genetically engineered to block RNA that gives rise to a protein called clusterin, which is thought to help tumors resist chemotherapy. OncoGenex’s bet is essentially that by disabling the clusterin tumor defense mechanism, a proven cell-killing chemotherapy agent like docetaxel ought to be even more effective at killing the cancer cells.
OncoGenex has some impressive data to support its concept. When given in combination with docetaxel chemotherapy in a study of 82 men, the OncoGenex drug helped men with terminal prostate cancer live a median of 23.8 months, about 6.9 months longer than they did on chemo alone, according to data presented at the American Society of Clinical Oncology’s annual meeting in 2009. Patients in that study, and across an array of five other studies, also showed signs of having reduced bone pain, which lasted for as long as three months of observation. That is a big deal, because men with this terminal form of prostate cancer often suffer as the tumors migrate into the bones, causing pain that’s so severe it can’t be consistently controlled with opioid-based pain medications like morphine.
OncoGenex believes it has a good scientific explanation for this, as its infusion drug has shown a good ability to be distributed into the bones, and the clusterin molecular target is overexpressed in bones. That means there’s a good chance the drug is seeping inside the bones, enabling chemo to penetrate in there and kill those particularly nasty tumors.
Getting really solid answers to questions like this take a lot of time, money, and risk. Back in 2010, the company designed a pair of clinical trials—called Synergy and Saturn—that were supposed to answer whether the drug can help men live longer, and reduce bone pain? OncoGenex ended up having to shut down the Saturn trial after finding it couldn’t get a consistent reading on baseline pain levels of patients, since it fluctuated so much during a one-week lead-in period to the trial. So OncoGenex and Teva, knowing that it would be easier to confirm the benefit of the Synergy trial with another study designed to measure survival time, replaced the 300-patient Saturn trial with a 630-patient trial called Affinity.
The main difference with the Affinity trial is that it was designed to combine OncoGenex’s drug with a different chemo agent, Sanofi’s cabazitaxel (Jevtana), and to recruit even sicker patients getting their second round of chemotherapy. While that Affinity study is going to take even more time and money to yield a result, OncoGenex is hoping that the results will be strong enough from the first trial that regulators will want to clear it for sale on that basis alone.
OncoGenex’s Synergy study uses the same combo of drugs, same schedule, and the same doses that it used in the earlier study that suggested such a strong survival advantage of 6.9 months, Cormack says. One difference is that new patients enrolling in this trial could have been previously exposed to some of the new agents like Dendreon’s sipuleucel-T (Provenge) and J&J’s abiraterone (Zytiga). Years have also gone by since the patients enrolled in the earlier study, so other factors could be at work to improve the life expectancy of patients who enroll today. The company will be able to declare success if the ongoing study improves survival time by about 15 percent over chemo alone, Cormack says. That means if you assume patients in this population will live about 20 months on chemo, then they’ll need to live about 23 months on chemo and the OncoGenex drug.
Until an answer like that arrives, OncoGenex just has to keep toiling on all kinds of behind-the-scenes work all biotech companies must do, Cormack says. The company has invested in a second drug, OGX-427, that gives the company another drug in its pipeline to work on besides custirsen. OncoGenex also raised about $54 million from investors in March to finance its clinical trials, and provide enough of a cash cushion to run the company into 2015—at least one more year after the critical results from the Phase III Synergy study arrive.
If the results are bad, the questions around OncoGenex will be about what else it has in the pipeline to remain viable. If the results are good, then the questions will be about regulatory filings, the size of the patient population, marketing strategy, competitive positioning, and potential expansion opportunities beyond prostate cancer. The data that will influence all of those factors just won’t arrive until the second half of 2013. It’s a moment Cormack says he’s looking forward to. “That’s obviously going to be a turning point for the company,” Cormack says.
