Phase III with Cancer Vaccine Lucanix

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NovaRx Moves into Phase III with Cancer Vaccine Lucanix

By Jennifer Boggs

Assistant Managing Editor

Hoping to repeat its Phase II success, privately held NovaRx Corp. launched a pivotal study of therapeutic vaccine Lucanix (belagenpumatucel-L) in non-small-cell lung cancer (NSCLC) patients under a special protocol assessment approved early this year.

Designated as STOP for its expected endpoints - survival, tumor-free survival, overall survival and progression-free survival - the trial is expected to enroll up to 700 patients with advanced-stage disease who have been treated with at least one prior platinum-based chemotherapy regimen. Patients will be randomized to receive Lucanix or placebo, administered intradermally, once-monthly for 18 months and then once at 21 months and at 24 months. Overall survival is the primary endpoint, while secondary endpoints will include progression-free survival, tumor response and quality of life.

The study could take up to three years, though NovaRx is "keeping our fingers crossed" that Lucanix will demonstrate efficacy before then, said Carissa Schumacher, director of corporate development for the San Diego-based firm.

An interim analysis is expected at the 430-patient mark.

The cancer vaccine space has yielded mixed results to date. Last month, Tampa, Fla.-based Biovest International Inc.'s BiovaxID (personalized anti-idiotype vaccine) met its primary endpoint in a Phase III non-Hodgkin's lymphoma (NHL) trial, but other firms haven't been as lucky. San Diego-based Favrille Inc.'s Specifid and Freemont, Calif.-based Genitope Corp.'s MyVax both have disappointed investors in the past several months after missing endpoints in NHL studies. And Oxford Biomedica plc, of Oxford, UK, missed the mark with its renal cancer vaccine Trovax in July. (See BioWorld Today, Dec. 26, 2007; May 28, 2008; July 14, 2008; and July 18, 2008.)

But the reason some of those failed is that they might not have "addressed the fundamental issue that cancer patients are immune-suppressed," Schumacher told BioWorld Today. That's why NovaRx's Lucanix aims specifically to block TGF-beta, a well-known immune suppressant.

Tumors secrete TGF-beta to "hide from the body's immune system," she said. Lucanix, which consists of four NSCLC cell lines that have been altered genetically to shut off their immune-suppressive responses, is designed to "remove that cloak," leaving cancer cells exposed to the immune system.

So far, results have been better than expected. Phase II results showed that 50 percent of patients with stable disease who received Lucanix after one front-line regimen of chemotherapy lived more than 44 months vs. fewer than 10 months to 12 months for those receiving standard care. Patients receiving Lucanix after zero to five prior chemo treatments had a one-year survival of 61 percent and a two-year survival of 41 percent, a striking improvement for late-stage patients, who typically have a one-year survival rate of less than 30 percent.

"We hope that Phase III [data] will be the same or will exceed Phase II data," Schumacher said.

Lucanix has fast-track status in the U.S.

NovaRx retains all rights to the program, which emerged from research conducted by Habib Fakhrai, company co-founder and president, and Daniel Shawler, NovaRx's vice president of operations. They discovered that TGF-beta was the "Achilles' heel of cancer," Schumacher said, and set about building a firm around that same approach, which might have potential in other cancer types beyond NSCLC.

In fact, the firm already has developed a second pipeline product, Glionix, which has completed a Phase I trial in brain cancer. The company is seeking orphan designation for that product.

Founded in 1996, NovaRx has grown up a little differently than other biotechs. While most private firms spend time attracting venture capital investments before seeking exits through initial public offerings or M&A, NovaRx has been able to concentrate solely on its pipeline, thanks to the investment of Justin Murdock, senior vice president of investments for Castle & Cook, a conglomerate with holdings across multiple areas, and the Dole Food Co.

Murdock joined the firm as its CEO and majority shareholder in 2006. At that time, NovaRx had completed some Phase II work with Lucanix, and "it was clear that we needed another investor," Schumacher said. She added that Murdock was swayed by the drug's impressive efficacy and promising toxicity profile and decided to invest in the firm.

That has "allowed us to keep our focus on the products," she said. Whereas with a syndicate of VCs on board, firms have to be concerned about exit strategies, with investors pushing for partnerships and mergers, Schumacher said, "and you never know where the technology might end up."

NovaRx's strategy lets it focus "on our greatest strength, which is the data and science, and build on that," she added.