Supercharged Herceptin Nears Pivot Point, as ImmunoGen, Roche Await Data on Breast Cancer “Smart Bomb”

12/7/09Follow @xconomy

ImmunoGen has been in business for 28 years without developing a single FDA approved drug. This week, after all those lean years, the Waltham, MA-based biotech (NASDAQ: IMGN) and its partner, Roche, are getting ready to show the world they have something big for patients with breast cancer.

The company is striving to develop the world’s first commercially successful “smart bomb” cancer drug, a dream that’s eluded cancer researchers for three decades. The drug from Roche, enabled by technology from ImmunoGen, combines the specific tumor-targeting ability of an engineered antibody, but (here’s the special part) attached to a chemical toxin that packs an extra tumor-killing kick. In this case, ImmunoGen and Roche have taken one of biotech’s most successful plain-vanilla antibodies, trastuzumab (Herceptin), and essentially supercharged it with one of those toxins.

Compelling evidence to support this drug, called T-DM1, has been mounting for two years, and this coming Saturday, researchers at the San Antonio Breast Cancer Symposium are expected to unveil data that could provide enough evidence for the companies to seek FDA approval. This has big ramifications for patients, and investors. The old workhorse version of trastuzumab, first approved by the FDA in 1998, is a mega-hit—with $5 billion in worldwide sales, even though it is only prescribed for about one-fourth of breast cancer patients with a certain gene mutation. The new souped-up version could be an even bigger seller, analysts say. And because ImmunoGen makes technology that can link any antibody drug to a toxin, it stands to collect sizable royalties not just on TDM1, but other drugs like it in the future. Savvy biotech investors are already picking up on this, as ImmunoGen stock has doubled this year.

“This is a big deal for the all the right reasons,” says ImmunoGen CEO Dan Junius. “It may be transformative.”

Dan Junius

Dan Junius

This drug first arrived on my radar back in April 2007, when I was at Bloomberg News. Ian Krop, an oncologist at the Dana-Farber Cancer Institute in Boston told me: “It’s unlikely this will cure breast cancer, but it’s got a good chance of being a really helpful weapon. We’re about as excited about this one as we can get this early in the game.”

Two months later, researchers showed a glimpse of what Krop was talking about. Four out of 10 patients in a study had their tumors shrink when taking T-DM1, researchers at the American Society of Clinical Oncology (ASCO) reported in 2007. That was striking because the tumor shrinkage happened in very sick patients whose cancer had spread through their bodies, and who had failed to respond to other therapies. Side effects were minimal.

Fast forward to the most recent ASCO conference in June. The numbers were a little more modest—only one out of four patients (25 percent) who got the experimental drug had partial or complete tumor shrinkage, according to a final analysis of 112 patients in a clinical trial. The most common severe side effects were lowered potassium levels and lowered counts of platelet cells in the blood. But importantly, researchers didn’t see the heart damage that has been observed in other trials of the standard trastuzumab.

This week in San Antonio, researchers will look at another 100-patient study of patients who are getting their third round of treatment. These are patients who failed to respond to the standard trastuzumab and a competing drug from GlaxoSmithKline called lapatinib (Tykerb). If this drug can show that it can shrink tumors for a high percentage of patients who have failed those other treatments, it could be enough for Roche to whip up an application for regulatory approval. If the data aren’t very persuasive, the companies will have to wait longer for the results of other studies, such as a more time-consuming 580-patient study that started enrolling patients in February.

When I stopped by his office a few weeks ago, Junius wouldn’t define for me how well T-DM1 must perform in the 100-patient study being presented in San Antonio. But if the data is “compelling,” he says, then Roche will file an application in 2010 for patients getting their third-line of treatment. Then the plan is to systematically start pushing the drug into progressively larger patient populations, he says. By 2012, the application could be ready for patients getting their second round of therapy, to be followed that year or shortly thereafter by patients getting their first round of treatment.

If all that goes according to plan, and the drug continues to show a relatively mild side effect profile for a cancer drug, then it could be used by the wider population of patients who have had their breast tumors surgically removed and appear healthy, but take what’s known as “adjuvant therapy” as a preventive measure to lower their risk of recurrence. Clinical trials that showed the original trastuzumab worked for those women have been a boon to Roche’s bottom line. Yet Junius says his partner is willing to cannibalize its own product if it can supplant the old one with something better.

“They really want the best compound possible in the market,” Junius says.

If T-DM1 can replace the original trastuzumab, that’s certainly the best-case scenario for ImmunoGen, because it stands to collect royalties on the new drug but gets nothing on the old one. The newer version is also likely to be higher priced, Junius says. But ImmunoGen doesn’t exactly stand to get super-rich either. Even though the ImmunoGen antibody-toxin linking technology is absolutely critical to the drug’s success, the company only stands to receive a “mid-single digit” percentage cut of worldwide product sales, Junius says.

When I said that sounded pretty puny compared to other deals I’ve seen small biotechs negotiate with big companies, Junius didn’t try to correct me, but he did place the deal in context. ImmunoGen basically wasn’t in nearly as strong of a bargaining position when the original deal was struck with Genentech in May 2000 as it is now, he says. (Genentech is now part of Roche).

“This deal was entered into in 2000, when success was just a gleam in their eye then,” says Junius, who became CEO on January 1. But given what is now known about the drug’s effectiveness, he acknowledges, “it’s an attractive deal for them, for sure.”

So ImmunoGen hopes to capitalize on the success in other ways. It has recently sold a pair of technology licenses for the linking technology to one of Roche’s competitors, Amgen. And ImmunoGen is trying to build up its own portfolio of supercharged antibodies for which it owns 100 percent of the commercial rights. To hear Junius tell the story, the success of TDM1 will assure that the next batch of deals will be struck on more favorable terms.

“Big Pharma is looking for all kinds of new solutions as they take a serious look at oncology and at antibodies,” Junius says. “We are having dialogue with everyone. [TDM1] has really been a means of gaining leverage. It’s really done a lot for us from a validation standpoint.”

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