Roche Breast Cancer Drug Trastuzumab-DM1 Review Turned Down By FDA

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Main Category: Breast Cancer
Also Included In: Pharma Industry / Biotech Industry;  Regulatory Affairs / Drug Approvals
Article Date: 27 Aug 2010 - 7:00 PDT

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The Food and Drug Administration (FDA) has issued a Refuse to File letter for accelerated approval of Roche's trastuzumab-DM1 (T-DM1) Biologics License Application, which was submitted in July 2010. Roche had requested accelerated approval for T-DM1 based on the results of a single-arm Phase II study. In that study one third of advanced HER2 positive breast cancer tumors shrank. The patients had received on average seven prior medications, including two HER2 targeted agents.

HER2 is the abbreviation for "human epidermal growth factor receptor 2". HER2 is involved in the growth of some cancer cells. A small percentage of breast cancers express HER2 protein.

Roche says it will continue with its ongoing Phase III EMILIA registration study. The company expects to liaise with the FDA and hopes for a global regulatory submission of T-DM1 by the middle of 2012.

For the FDA to consider a drug candidate for accelerated approval there must be an identified patient population with a life-threatening disease and limited treatment choices (unmet need). The drug's safety and efficacy data needs to reasonably predict a likely clinical benefit for the patient.

Roche had felt it was appropriate to submit a Biologics License Applicatio after a pre-submission meeting with the FDA in March 2010.

After reviewing the Biologics License Application, the FDA concluded that T-DM1 "did not meet the standard for accelerated approval because all available treatment choices approved for metastatic breast cancer, regardless of HER2 status, had not been exhausted in the study population."

Hal Barron, M.D., Head of Global Development and Chief Medical Officer for Roche, said:

We firmly believe in the potential of T-DM1 as a novel HER2 targeted option and remain fully committed to its ongoing development.

Roche says it will submit data from the amended Phase III randomized EMILIA study to support a global regulatory submission in the middle of 2012.

The EMILIA study compares T-DM1 to lapatinib in combination with capecitabine in people with advanced HER2 positive breast cancer whose disease has worsened after receiving initial treatment.

About T-DM1

• T-DM1 is an antibody-drug conjugate (ADC), also known as an armed antibody, being studied for advanced HER2 positive breast cancer.
• T-DM1 attaches trastuzumab and the chemotherapy DM1 together using a stable linker, which is designed to keep T-DM1 in one piece until it reaches specific cancer cells.
• The antibody (trastuzumab) binds to the HER2 positive cancer cells, and is thought to block out-of-control signals that make the cancer grow while also calling on the body's immune system to attack the cells.
• Then, once T-DM1 is absorbed into those cancer cells, it is designed to destroy them by releasing the DM1. Genentech licenses technology for T-DM1 under an agreement with ImmunoGen, Inc.

Roche has had a series of recent setbacks:

• Diabetes drug taspoglutide's approval was delayed after safety concerns.
• Rheumatoid arthritis experimental drug ocrelizumab was discontinued.
• Cancer medication Avastin failed in late-stage prostate cancer trials.
• UK regulators rejected Avastin for the treatment of bowel cancer due to costs.

According to The Wall Street Journal, Roche's share prices have fallen by over 20% this year. There is growing concern about drugs in the pipeline, as well as global austerity programs which may affect the company's profits.

However, unlike many other pharmaceutical companies, Roche does not face short-term patent losses; it has comparatively more time to develop new drugs.

Sources: Roche, Wall Street Journal

Written by Christian Nordqvist


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