The First Conjugated Monoclonal Antibody From ImmunoGen’s (IMGN) Technology To Reach That Stage
In
Today’s news, Genentech, a member of the Roche Group, announced that
the company has, indeed, submitted a Biologics License Application (BLA)
to the FDA for trastuzumab-DM1 (T-DM1). The drug’s technology is
licensed from ImmunoGen (IMGN). The BLA is for approval of T-DM1 in
people with advanced HER2-positive breast cancer who have previously
received multiple HER2-targeted medicines and chemotherapies. This
submission is based on the results of a Phase 2 study, which showed
T-DM1 shrank tumors in one-third of women who had received on average
seven prior medicines for advanced HER2-positive breast cancer.
This
submission was expected and Prohost mentioned it time and time again,
the latest was in Prohost Letter #303 posted on Prohost website on
Tuesday when we wrote: “Seeing patients who became resistant to its drug
herceptin respond to T-DM1, Roche became excited and motivated to ask
the FDA for an early approval of the drug. Patients who had previously
received, on average, seven different drugs for their advanced breast
cancer had an objective response to treatment with T-DM1. Among the
responders were a substantial number of patients with recurrent disease
who became resistant to Roche’s blockbuster drug Herceptin. How could
anybody believe that ImmunoGen, which has a pipeline of successfully
conjugated drugs, be bad?”
The Prohost Letter wrote, “ImmunoGen’s
weapon resides in its technological capability that succeeded for the
first time in history in designing and developing safe and effective
conjugated monoclonal antibody drugs. ImmunoGen’s lead drug
Trastuzumab-DM1 (T-DM1) is a monoclonal antibody against HER2 neu breast
cancer loaded with the cancer-cell killing agent, DM1. The drug has
demonstrated efficacy in patients suffering from her2 neu recurrent
resistant breast cancer patients.”
In Genentech/Roche press
release, Hal Barron, M.D., executive vice president, Global Development
and chief medical officer said: “While we’ve made great strides in
treating HER2-positive breast cancer, there is a group of people whose
breast cancer will come back after many treatments, leaving them with
very limited options. Data from studies have shown that T-DM1 shrank
tumors in these people, so we are excited to have submitted this
application to the FDA in hopes of offering a potential new medicine to
people with this type of breast cancer.”
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.
A Phase 2 study
known as TDM4374g, designed to assess single-agent T-DM1 in 110 women
with HER2-positive advanced breast cancer whose disease had worsened
after receiving at least two prior HER2-targeted treatments Herceptin®
(trastuzumab) and lapatinib) in the metastatic setting, as well as an
anthracycline, a taxane and capecitabine, demonstrated the following
results:
-- T-DM1 shrank tumors in 33 percent of women with
advanced HER2-positive breast cancer that had worsened following
treatment with an average of seven prior medicines for metastatic
disease.
-- Most side effects were mild (Grade 1-2) and similar to those observed in previous clinical trials of T-DM1.
More
trials of T-DM1 are planned for the drug, either alone or in
combination with other medicines. An ongoing Phase 3 trial, known as
EMILIA, is comparing T-DM1 to lapatinib in combination with capecitabine
in people with advanced HER2-positive breast cancer whose disease has
worsened after receiving initial treatment. Also, a planned Phase 3
study, MARIANNE, will compare both T-DM1 alone and T-DM1 in combination
with pertuzumab to Herceptin in combination with a taxane chemotherapy
in people with advanced HER2-positive breast cancer who have not been
previously treated for advanced disease.
Genentech has opened a
T-DM1 Patient Access Study in the United States to provide a specific
group of people with advanced HER2-positive breast cancer access to
T-DM1 while Genentech seeks U.S. approval.
Genentech licenses technology for T-DM1 from ImmunoGen (IMGN).
For the complete press release click: http://www.roche.com/media/media_releases/med-cor-2010-07-07.htm
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