CHICAGO - T-DM1 lived up to its star billing at ASCO. The "armed antibody" from Roche's Genentech subsidiary was in the center ring at ASCO as the wraps came off Phase III data, delaying disease progression in metastatic breast cancer patients by several months while reducing the risk of adverse events. And in the process investigators highlighted antibody-drug conjugates as the hot new technology in cancer drug development.
T-DM1 delayed tumor progression by an average of 3.2 months. Median progression-free survival was 9.6 months for the T-DM1 arm while standard therapy delivered a median PFS rate of 6.4 months. Close to two thirds of the patients taking T-DM1--which was designed with ADC technology provided by ImmunoGen--were alive after two years, while slightly fewer than half of the patients receiving a Tykerb/Xeloda combo survived the same period.
The interim overall survival data fell short of statistical significance, but Duke investigator Kimberley Blackwell said that the data clearly demonstrated that using an antibody to guide a highly toxic dose of chemo right to the tumor target works as expected. Final overall survival rates will be determined in 2014. Blackwell also highlighted that the targeted treatment delivered a better quality of life for patients, saving them from the toxic effects of broadly delivered chemotherapy. Patients take T-DM1, for example, didn't lose their hair.
T-DM1 is an elegantly crafted weapon that relies on technology in-licensed from ImmunoGen, which stands to gain mid-single digit royalties on the product. An antibody linked to a highly toxic drug delivers the payload right in the target. That may sound simple, but it's taken 30 years to get the technology right. And now it's a must-have approach for every big pharma company in oncology.
Roche ($RHHBY) has already been rebuffed once by the FDA, which handed back its new drug application for the treatment after refusing to consider an approval based on promising mid-stage data. And there's still some question whether regulators will insist on a final set of survival data before approving the drug. Given the targeted design of the drug--which zeroes in on HER2-positive patients--and the agency's insistence that it is becoming more flexible on its review of life-saving therapies, though, Roche is given good odds that it can now win a regulatory OK. The pharma giant plans to file for an approval later in the year.
Roche is already bumping up against the PDUFA date for pertuzumab, which is likely to be given to breast cancer patients in combination with Herceptin. If approved, T-DM1 could enter into that therapeutic regimen, offering advanced-stage patients another option and raising the possibility that it may eventually help dramatically change the prognosis for earlier-stage patients.
"I think it is the first of many antibody drug conjugates to follow," Blackwell told a big audience of reporters in Chicago. And Roche is investing a considerable amount of time and money to find out.
Genentech has eight other ADCs in the clinic, says Dietmar Berger, vice president in product development oncology at Genentech. And it has a total of 25 ADCs in the pipeline, with a number of programs built with technology provided by Seattle Genetics, a pioneer in the field.
"Genentech is a company which is really built on the program," Berger tells FierceBiotech. "Personally, I believe it's going to revolutionize therapy." And a combo study of pertuzumab and T-DM1 is in the works.
- here's the press release