Viruses that are genetically engineered to fight tumors, without harming healthy cells, may sound like sci-fi. But San Francisco-based Jennerex Biotherapeutics has started gathering some intriguing—albeit quite preliminary—clinical trial evidence that suggests this approach may be helping liver cancer patients live longer, Xconomy has learned.
Jennerex, which I first wrote about here in September, flies below the radar of most biotech pros, and has collected its $45 million in financing from sources few in biotech have heard of. And to be clear, the data on Jennerex’s oncolytic virus therapy, JX-594, is about as far from scientific peer-review as you can get. It’s based on a small number of patients—26 so far—with liver cancer. More patients still need to enroll, more follow-up time is required, and the findings haven’t yet been presented at a scientific meeting. But if the early trends described by Jennerex CEO David Kirn hold up over time, this could be shaping up as the kind of result that cancer researchers will buzz about for a long time.
“This trial is what everybody has been waiting for,” says Kirn, an oncologist and former VP of clinical research at Onyx Pharmaceuticals (NASDAQ: ONXX). “Everybody knew oncolytic viruses had been shown to be safe, and they show some anti-tumor activity, although not to the degree we’re seeing it. Everybody is waiting for randomized survival data. Nobody has shown data like this before.”
Before diving into the nitty gritty details, a little background is required. Jennerex is one of a handful of companies actively developing viruses that are genetically modified to replicate strictly inside tumors. These injectable viruses are designed to work their way into tumors, where they replicate very fast, causing the cancer cells to burst. The Jennerex treatment is also made to target the blood vessels that nourish the tumor, and send signals that alert the immune system to seek and destroy any residual cancer cells that might have been able to evade the virus. Many companies—Onyx Pharmaceuticals and Cell Genesys—have tried similar approaches and no one has yet won an FDA approval. But the field saw a renewed burst of interest last month when biotech giant Amgen (NASDAQ: AMGN) agreed to pay as much as $1 billion to acquire a new player in the field, Woburn, MA-based BioVex.
Jennerex’s drug, JX-594, isn’t as far along in clinical trials as BioVex’s. The Jennerex treatment has gone through a series of initial clinical trials in a total of 96 patients to date, mostly to establish safety, and to study the way the virus works, Kirn says. But the really interesting stuff is emerging from a mid-stage study, which has enrolled 26 patients since early 2009, Kirn says.
The study is designed to enroll patients with primary liver cancer, known as hepatocellular carcinoma. Patients in the U.S., who get one of the standard drugs, Bayer and Onyx’s sorafenib (Nexavar) are generally thought to have a median life expectancy of 10.5 months, while patients in Asia typically have a life expectancy of about five to six months, Kirn says.
Patients in the study were randomly assigned to get either a high dose or a low dose of the Jennerex treatment. Those who enrolled got three doses over a one-month period, and then were followed up.
The study began in early 2009, and still needs about four more patients to reach its full enrollment target of 30, Kirn says. The primary goal of the trial is to see how long the Jennerex drug can keep tumors from spreading. But one of the secondary goals looks at the key question in all cancer trials—how long are patients actually living?
Early returns show that a handful of the original 26 are still alive after more than two years of follow-up, and “close to 10″ have made it past one year, Kirn says. Not enough of the 26 patients have died yet for statisticians to calculate the median survival time for patients on this study. But patients on the low-dose group appear to be living about the same amount of time as patients on the Bayer/Onyx drug, and there is a statistically significant advantage for those on the high dose of the Jennerex treatment, according to an interim analysis of the data, Kirn says.
The traditional way to visualize the trend of a cancer survival trial over time—expressed through what’s known as a Kaplan-Meier curve—shows a “striking advantage” for the Jennerex high dose group, compared with the low-dose, and historical studies of patients on other therapies, Kirn says.
Researchers have seen a safety profile consistent with what was observed in earlier clinical trials, Kirn says. Since the drug is designed to partly work by fighting tumor-feeding blood vessels, I asked whether Jennerex has seen any serious side effects, like bleeding episodes, which have been observed with another drug that works to choke off blood flow to tumors—Genentech’s bevacizumab (Avastin).
“We haven’t seen it to date,” Kirn says. “It’s something we watch for very carefully. To date (JX-594) has been extremely selective to the tumor.”
Any time a study this small shows a provocative early result, researchers naturally want to see if it can be confirmed as the real thing in a much larger study. Jennerex’s plan is to complete enrollment in the small study early this year, continue to follow the patients, and hopefully present more statistically mature, detailed results at the American Association for the Study of Liver Diseases meeting in November in San Francisco, Kirn says.
Before that, Jennerex hopes to charge ahead with a Phase 2b study in relapsed, treatment-resistant liver cancer patients, which could be considered a pivotal study in the eyes of the FDA, providing the basis for the drug to be sold in the U.S., Kirn says. That bigger study should get underway in mid-2011, followed by another pivotal study in newly-diagnosed patients, which could get underway in the first half of 2012.
Jennerex presented some of this early data in private meetings with investors at the JP Morgan Healthcare Conference last month in San Francisco, but awareness really took off after Amgen wrote its big check for BioVex on January 24th. Like anything in biotech, the nanosecond some new technology gets validation, investor instinct is to look for companies with similar technology that can essentially be found on the bargain basement rack. So a lot of people suddenly started paying attention to Jennerex and oncolytic virus technology.
“We have always believed very strongly that this was a breakthrough platform for cancer, but have we gotten more calls from bankers and investors since the BioVex news? Yes,” Kirn says. “It does give some sense of the importance of this technology to the outside world.”
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