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Ariad Eagerly Awaits the Big Show, ASCO, To Display Cancer Trial Results

Xconomy Boston — 

Ariad Pharmaceuticals’ stock has surged 73 percent since New Year’s Day, so you could say CEO Harvey Berger is having a better-than-average year. The Cambridge, MA-based cancer drug developer has seen its market valuation eclipse $1 billion, on a wave of anticipation heading into what could be the most important medical meeting in his company’s 20-year history.

And yet he says he’s still not satisfied.

“My view is that the stock is still way underpriced,” Berger says.

We’ll all find out soon enough if doctors and investors agree with the insider’s take. For now, everybody following Ariad (NASDAQ: ARIA) is waiting in suspense for the data to validate this recent stock surge.

The story hinges on Ariad’s ridaforolimus (pronounced Rid-uh-for-AH-luh-muss, or just “Rid-uh” for short). This is an oral pill which Ariad, in collaboration with Merck, has developed to block the mTOR protein, a master biological switch that allows tumors to grow and thrive.

Doctors and investors are eagerly anticipating the results from the most rigorous test of this drug yet. The study enrolled 711 patients with sarcomas, who had already had their disease stabilize after a prior round of chemotherapy, and then compared how well they did on a daily maintenance dose of the Ariad drug, compared with a placebo. Results are expected to be presented in front of a roomful of doctors at 4:30 pm Central Time, June 6, at the American Society of Clinical Oncology’s (ASCO) annual meeting in Chicago.

The world already knows that this trial, called Succeed, has succeeded. The drug met its primary goal of keeping tumors from spreading for a longer period of time than a placebo, according to an Ariad statement in January. Patients were able to keep their tumors in check for a median time of 17.7 weeks on the Ariad drug, compared with 14.6 weeks on a placebo. That figure came from an independent panel of expert radiologists. Investigators at the clinical sites, who reviewed scans of patients, took a more favorable view. Doctors reported that patients on the Ariad drug actually had their tumors remain in check for a median of 22.4 weeks, compared with 14.7 weeks for the placebo group.

Harvey Berger

That sounded like a pretty modest clinical advantage to me, even in the world of cancer drugs, where the benefits of new treatments are often pretty incremental. But Berger insisted that it’s meaningful to doctors and regulators. Side effects were modest—mouth sores, fatigue, diarrhea and a drop in clot-forming platelet cells. That’s a much milder side-effect profile than the alternative, which is another round of cell-killing chemotherapy, Berger noted. Most importantly, the FDA agreed that this clinical goal—known as progression-free survival or PFS—could serve as the primary endpoint for success in this trial.

Of course, overall survival time is the gold standard measurement of success in cancer drug development, so many of the inquiring minds in attendance at ASCO will want to know how this drug is performing on that score. Ariad is gathering this data, and reported on a bit of the data in an abstract that ASCO posted online May 18 in advance of the annual conference.

The results so far, based on the first 313 total deaths in a study of 711 patients, showed that patients on the Ariad drug lived a median time of 88 weeks, compared with 78.7 weeks on the placebo, according to the abstract. Researchers said this suggested a “trend” toward an improvement in overall survival, although they didn’t disclose a p-value reading, which could demonstrate whether or not the result can be considered a statistical fluke.

The survival data that appeared in the abstract was current as of December, but has been updated for the June 6 presentation, Berger says. The new batch of data will be current through April, meaning doctors had five more months of follow-up time to record more deaths, so statisticians can run more robust calculations on how the drug did versus the placebo. Berger wouldn’t say how many total deaths will be reported on at ASCO, only that it will be “more than 313.”

What’s important is that the study hit its main goal on progression-free survival in a way that was statistically convincing, and that benchmark appeared to be predictive of an improvement in survival times, Berger says. “This is exactly the kind of data we wanted to see, and expected to see,” he says.

Merck plans to submit an application later this year to the FDA for approval to start marketing the drug in the U.S., so it’s possible the treatment could be cleared for sale in 2012. If approved, the Ariad drug would be the second mTOR inhibitor approved by the FDA, after Novartis’ everolimus (Afinitor) for kidney cancer.

Merck is picking up the tab for development costs and the commercial push for the Ariad drug, and has agreed to pay Ariad “substantial, tiered double-digit royalties” on worldwide sales, Berger says. If the drug does well in its initial group of patients, you can bet there will be more interest in testing it out against other tumor types, an effort that’s already well underway at Merck. Analysts at the ASCO meeting will be taking the temperature of physician enthusiasm, and penciling out their sales models accordingly, to help them extrapolate where Ariad’s valuation is headed from here.

One other Ariad drug, ponatinib, will also have a lesser role to play at this year’s ASCO. Data on that treatment for chronic myeloid leukemia is still in the early stages, but some analysts consider that to be more of a future driver of Ariad’s value than ridaforolimus. Analyst Eun Yang of Jefferies & Co. has noted that ponatinib could generate $205 million in U.S. sales by 2017, while Ariad’s cut of royalties from Merck’s sales of ridaforolimus could bring in about $72 million that year.

Berger wouldn’t say which one he thinks is more valuable to the company, but that both are critical to the company’s plan to grow from an R&D-only shop into a diversified company that also markets its own products.

“By the end of next year, I expect Ariad will have two drugs on the market which were internally discovered and developed,” Berger says. “Not many companies can say that.”