Two years after the Food and Drug Administration refused to review T-DM1 for accelerated approval, Roche/Genentech Inc. has resubmitted the application with a statistically significant overall survival advantage in hand – FDA’s gold standard for oncology approvals.
The company announced Aug. 27 that it had submitted a biologics license application (BLA) to the FDA for the antibody drug conjugate trastuzumab emtansine, a combination of the monoclonal antibody trastuzumab (Herceptin) with the potent cytotoxic agent DM1, connected by a stable linker based on technology licensed from ImmunoGen Inc.
Genentech expects to submit a marketing authorization application to the European Medicines Agency soon.
[Editor’s note: Genentech has clarified that the updated overall survival analysis was not included in the initial BLA resubmission. It will be provided to FDA during its review of the application.]
The company also announced further results from the EMILIA study, showing T-DM1 had a statistically significant overall survival benefit in HER2-positive metastatic breast cancer, compared with GlaxoSmithKline Inc.’s lapatinib (Tykerb) in combination with capecitabine (Xeloda). Roche did not release actual figures, which will be presented at an upcoming medical meeting.
Dr. Kimberly Blackwell
At the American Society for Clinical Oncology meeting in June, EMILIA authors showed a 3.2-month median progression-free survival benefit. Lead investigator Dr. Kimberly Blackwell, professor of medicine and assistant professor of radiation oncology at Duke Cancer Institute, Duke University, Durham, N.C., also said at the time there was a trend toward an overall survival improvement.
Analysts were not surprised at the news, given the progression-free survival advantage. J.P. Morgan said in an Aug. 27 note that its forecasts already expected a survival benefit in many treatment settings and that while markets reacted favorably to the news, ImmunoGen "already gets credit for this highly promising product."
Priority Review Expected
The positive data also should allow for a quick FDA approval. Priority review would mean action by late February 2013, but J.P. Morgan’s Cory Kasimov indicated that approval could come earlier. The FDA has approved several drugs ahead of the user fee deadline over the past year.
That would be a welcome change for T-DM1 after the FDA refused to file Genentech’s accelerated approval application for the product in 2010. Indeed, the company made the refuse-to-file announcement exactly 2 years before announcing the overall survival benefit – Aug. 27, 2010.
That application was based on the results of one single-arm phase II trial in 110 patients. Tumors shrank in one-third of women with advanced HER2-positive breast cancer, who had received on average seven prior medicines, but the FDA said the filing did not meet the standards for accelerated approval because the company had not exhausted all available treatment options for metastatic breast cancer in the study population.
Roche plans to launch T-DM1 next year as a second-line therapy, although physicians are expected to use it as a first-line therapy, company officials said during an analyst briefing at ASCO in June.
T-DM1 is expected to eventually replace trastuzumab as the standard of care and as the cornerstone of Roche’s breast cancer portfolio. An early 2013 approval will give Roche time to establish the product before the introduction of trastuzumab biosimilars, expected in Europe in 2014 and in the United States in 2019.
The company is already studying T-DM1 in combination with pertuzumab (Perjeta), which could potentially eliminate the need for chemotherapy. Pertuzumab was approved in June for use with trastuzumab and chemotherapy in previously untreated HER2-positive metastatic breast cancer that has recurred after adjuvant or neoadjuvant therapy.
Roche also is expected to be among the first to test a new accelerated approval draft guidance using pathologic complete response to support accelerated approval in neoadjuvant breast cancer. It announced plans for a study testing T-DM1 and pertuzumab just after the draft guidance was released.
The company will face concerns about pricing, especially with the combination of the two targeted agents. But at an ASCO briefing, Roche COO Pascal Soriot pointed out that there will be safety advantages. "There will be a lot of savings for the systems and we need to price that in how we price T-DM1," he said.
Editor’s note: This story appears courtesy of "The Pink Sheet," a weekly Elsevier publication covering pharmaceutical business and policy issues. To learn more, contract customer care at 800-332-2181 or sign up for a free trial.
* This story was updated on 8/28/12 per clarification from Genentech.