The Genentech Inc. unit of Roche AG announced that its Phase III (EMILIA) trial of Immunogen Inc.-partnered asset trastuzumab emtansine (T-DM1) showed positive results. Patients randomized to treatment with T-DM1 had a significantly longer duration of progression-free survival than those receiving the control therapy, lapatinib plus capecitabine.

Overall survival was also an objective of the trial, but that endpoint was "not mature yet," according to Immunogen CEO Dan Junius, speaking in a conference call Friday morning.

Roche plans to apply for marketing approval of tastuzumab emtansine for second- and third-line HER2 positive metastatic breast cancer in the U.S. and Europe based on those results, and Immunogen stock (NASDAQ:IMGN) was buoyed up 65 cents, to close at $14.39 Friday.

"This is the first antibody-drug conjugate for a high incidence solid tumor indication," Junius said.

T-DM1 is also on the verge of becoming the first successful compound developed from Immunogen's tumor-activated prodrug (TAP) technology for linking cytotoxic payloads to targeting antibodies. The Waltham, Mass.-company recognized long ago that Genentech's trastuzumab antibody was a good match for that technology. The two companies teamed up in 2000 to develop T-DM1, which combines trastuzumab with Immunogen's proprietary cytotoxic agent emtansine.

Genentech received exclusive worldwide rights to commercialize anti-HER2 targeting products using Immunogen's TAP platform, paying $2 million up front plus milestone payments up to $40 million and royalties on net sales.

Getting it to the point of marketing registration has taken 12 long years, enough time for empires to rise and fall in the biotech world. T-DM1 entered the clinic in 2006, with Genentech taking full responsibility for clinical development.

Genentech's patience has paid off. In September 2011 the companies reported positive full results from its Phase II trial of T-DM1 in HER2-positive metastatic breast cancer. In a group of 137 patients, median progression-free survival was significantly greater for patients who received T-DM1 than standard-of-care therapy, Herceptin plus chemotherapy (14.2 months vs. 9.2 months). T-DM1 reduced the probability of disease progression or death by 41 percent. (See BioWorld Today, Sept. 27, 2011.)

The response rate for single-agent T-DM1 was 64.2 percent, compared to 58 percent for the Herceptin-plus-chemotherapy arm.

T-DM1 beat Herceptin at safety, too. Patients who received T-DM1 had about half the incidence of severe adverse events as those who received the standard-of-care therapy (46.4 percent vs. 89.4 percent)

Given the strong Phase II results, it would have been surprising if T-DM1 had failed to perform in Phase III. Fortunately, Immunogen and Roche can breathe a sigh of relief. Their 12-year investment in the drug seems about to pay off.

Herceptin sales were $5.7 billion in 2010, and trial results suggested that the addition of the cytotoxic compound emtansine enhances the efficacy of Herceptin, giving it a potentially very large market. Royalties on such a successful product could make a big difference in Immunogen's bottom line.

"I don't think that would bring us to profitability in the near term," Junius said. However, the success of T-DM1 has important implications for the numerous partnered and unpartnered products in Immunogen's pipeline. Similar outcomes for those programs could easily put Immunogen in the big leagues.

J.P. Morgan's Cory Kasimov noted that the HER2-positive breast cancer market was becoming increasingly segmented. "In addition to T-DM1, three other products could soon join Herceptin and Tykerb in the evolving Her2+ space," Kasimov wrote.

Oppenheimer's Bret Holly looked forward to detailed results at a future meeting and anticipated strong results for T-DM1 in first-line metastatic breast cancer from the Phase III MARIANNE trial. "Based on positive Phase IIb PFS results in first-line mBC, we see a high probability T-DM1 will show a strong PFS benefit over Herceptin plus taxane in MARIANNE," Holly wrote.

Immunogen also announced the initiation of its Phase II (NORTH) trial of IMGN901 in first-line small-cell lung cancer. The trial will assess efficacy and safety of IMGN901 for first-line treatment of extensive disease in small-cell lung cancer by enrolling 120 patients to be randomized to IMGN901 plus carboplatin and etoposide or carboplatin and etoposide alone. The primary endpoint of the trial will be progression-free survival. Secondary endpoints include PFS at six months, overall survival at 12 months, time to progression, overall survival and overall response rate.

Junius called the NORTH trial "very important to the company" in terms of its internal pipeline. Immunogen is advancing antibody-drug conjugates based on the TAP platform in a number of indications including non-Hodgkin lymphoma, solid tumors, blood cancers and more.