FDA Approves Genentech’s Kadcyla (Ado-Trastuzumab Emtansine), the First Antibody-Drug Conjugate for Treating HER2-Positive Metastatic Breast Cancer

SOUTH SAN FRANCISCO, Calif. -- (BUSINESS WIRE) -- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has approved Kadcyla™ (ado-trastuzumab emtansine or T-DM1) for the treatment of people with HER2-positive metastatic breast cancer (mBC) who have received prior treatment with Herceptin^® (trastuzumab) and a taxane chemotherapy. Kadcyla is the fourth medicine from Genentech to receive FDA approval for people with advanced cancers within the past two years.

An antibody-drug conjugate (ADC) is a new kind of targeted cancer medicine that can attach to certain types of cancer cells and deliver chemotherapy directly to them. Kadcyla is the first FDA-approved ADC for treating HER2-positive mBC, an aggressive form of the disease.

“Kadcyla is an antibody-drug conjugate representing a completely new way to treat HER2-positive metastatic breast cancer, and it helped people in the EMILIA study live nearly six months longer,” said Hal Barron, M.D., chief medical officer and head, Global Product Development. “We currently have more than 25 antibody-drug conjugates in our pipeline and hope this promising approach will help us deliver more medicines to fight other cancers in the future.”

Kadcyla is made up of the antibody, trastuzumab, and the chemotherapy, DM1, joined together using a stable linker. Kadcyla combines the mechanisms of action of both trastuzumab and DM1, and it is the first Genentech ADC approved by the FDA. Genentech has studied ADC science for more than a decade and has eight ADCs in Phase I or Phase II studies for different types of cancer.

Kadcyla will be available to people in the United States within two weeks. As part of this approval, Genentech plans to initiate patient assistance programs for people taking Kadcyla through Genentech Access Solutions. These programs help people who might not be able to afford this medicine. People who do not have health insurance, or who have reached the lifetime limit set by their insurance company, might qualify to receive Kadcyla free of charge. For people with insurance, Genentech Access Solutions offers co-pay assistance programs to help with the out-of-pocket costs of their medicine, including a co-pay card for those with private insurance. The card pays 80 percent of out-of-pocket costs for people who qualify (up to $9,000 or $24,000 per year, depending on the person’s income).

Doctors can contact Genentech Access Solutions at (888) 249-4918. More information is also available at http://www.Genentech-Access.com.

Roche has also submitted a Marketing Authorization Application to other regulatory authorities around the world, including the European Medicines Agency (EMA), for Kadcyla for the treatment of people with HER2-positive mBC. This application is currently under review by the EMA.

Kadcyla Efficacy in HER2-positive mBC

The FDA approval of Kadcyla is based on results from EMILIA (TDM4370g/BO21977), an international, Phase III, randomized, open-label study comparing Kadcyla alone to lapatinib in combination with Xeloda^® (capecitabine) in 991 people with HER2-positive locally advanced breast cancer or mBC who had previously been treated with Herceptin and a taxane chemotherapy. Results include:

• The study met both co-primary efficacy endpoints of overall survival and progression-free survival (PFS; as assessed by an independent review committee).
• People who received Kadcyla lived a median of 5.8 months longer (overall survival) than those who received the combination of lapatinib and Xeloda, the standard of care in this setting (median overall survival: 30.9 months vs. 25.1 months).
• People receiving Kadcyla experienced a 32 percent reduction in the risk of dying compared to people who received lapatinib and Xeloda (HR=0.68; p=0.0006).
• People who received Kadcyla lived significantly longer without their disease getting worse (PFS) compared to those who received lapatinib plus Xeloda (HR=0.65, 35 percent reduction in risk of disease worsening or death, p<0.0001; median PFS 9.6 months vs. 6.4 months).
• No new safety signals were observed and adverse events (AEs) were consistent with those seen in previous studies, with fewer people who received Kadcyla experiencing Grade 3 or higher (severe) AEs than those who received lapatinib plus Xeloda (43.1 percent vs. 59.2 percent).
• For people receiving Kadcyla, the most common (occurring in more than 2 percent of participants) Grade 3 or higher AEs were low platelet count (14.5 percent), increased levels of enzymes released by the liver and other organs (8.0 percent), low red blood cell count (4.1 percent), low levels of potassium in the blood (2.7 percent), nerve problems (2.2 percent) and tiredness (2.5 percent).

About Kadcyla (pronounced kad SIGH luh); ado-trastuzumab emtansine (pronounced ADD oh traz TOO zuh mab em TAN zine)

Kadcyla is an ADC being studied in HER2-positive cancers. It is the first ADC to result from Genentech’s 30 years of HER2 pathway research and the third medicine Genentech has developed for the treatment of HER2-positive breast cancer.

Like Herceptin, Kadcyla binds to HER2-positive 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 cancer cells. Once Kadcyla is taken up by those cells, it is designed to destroy them by releasing the DM1 inside the cells.

Genentech licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

Kadcyla Indication Statement

Kadcyla™ (ado-trastuzumab emtansine) is approved as a single medicine for the treatment of people with HER2-positive metastatic breast cancer (mBC) who have received prior treatment with Herceptin^® (trastuzumab) and a taxane chemotherapy. People should either:

• Have already been treated for their metastatic cancer, or
• Have had their early-stage cancer come back during or within six months after they completed a course of treatment following surgery.

Important Safety Information

Kadcyla is not the same medicine as Herceptin.

There are possible serious side effects of Kadcyla. Patients must contact their doctor right away if they experience any of these symptoms. The patient’s doctor may do tests before starting Kadcyla and before each dose to monitor for these side effects. Kadcyla treatment may be stopped or the dose may be lowered if the patient experiences any of these side effects.

Liver Problems

• Kadcyla may cause severe liver problems that can be life-threatening. Symptoms of liver problems may include vomiting, nausea, stomach pain, dark urine or itching.

Heart Problems

• Kadcyla may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). Symptoms may include swelling of the ankles or legs, shortness of breath, cough or rapid weight gain of greater than five pounds in less than 24 hours.

Pregnancy

• Receiving Kadcyla during pregnancy can result in the death of an unborn baby and birth defects. Birth control should be used while patients receive Kadcyla and for six months after their last dose of Kadcyla.
• If patients are exposed to Kadcyla during pregnancy, they must contact their healthcare provider right away; they are also encouraged to enroll in the MotHER Pregnancy Registry by contacting (800) 690-6720.
• If patients are mothers who are breastfeeding, they should talk with their doctor about either stopping breastfeeding or stopping treatment with Kadcyla.

Additional Possible Serious Side Effects of Kadcyla

Lung Problems

• Kadcyla may cause lung problems, including inflammation of the lung tissue, which can be life-threatening. Signs of lung problems may include trouble breathing, cough, tiredness and fluid in the lungs.

Infusion-Related Reactions

• Symptoms of an infusion-related reaction may include one or more of the following: the skin getting hot or red (flushing), chills, fever, trouble breathing, low blood pressure, wheezing, tightening of the muscles in the chest around the airways or a fast heartbeat. The patient’s doctor will monitor the patient for infusion-related reactions.

Low Platelet Count

• Low platelet count may happen during treatment with Kadcyla. Platelets are cells in the blood that help the blood clot.

Nerve Damage

• Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, or muscle weakness or loss of muscle function.

Skin Reactions Around the Infusion Site

• Kadcyla may leak from the vein or needle and cause reactions such as redness, tenderness, skin irritation, or pain or swelling at the infusion site. If this happens, it is more likely to happen within 24 hours of the infusion.

HER2 Testing and Kadcyla

Patients must have a HER2 test to determine if their cancer is HER2-positive before taking Kadcyla, as benefit has only been shown in patients whose tumors are HER2-positive.

Most Common Side Effects of Kadcyla

In clinical studies, the most common side effects seen in people taking Kadcyla were tiredness, nausea, pain that affects the bones, muscles, ligaments and tendons, low platelet count, headache, liver problems and constipation.

The most common severe side effects of Kadcyla were low platelet count, liver problems, low levels of red blood cells, nerve problems, low levels of potassium in the blood and tiredness.

Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients and caregivers may also report side effects to Genentech at (888) 835-2555.

For full Prescribing Information and Boxed WARNINGS on Kadcyla, please visit http://www.gene.com.

About Breast Cancer

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 235,000 people in the United States will be diagnosed with breast cancer, and 40,000 will die from the disease in 2013. In HER2-positive breast cancer, increased quantities of the Human Epidermal growth factor Receptor 2 (HER2) are present on the surface of the tumor cells. This is known as “HER2 positivity” and affects approximately 25 percent of people with breast cancer. HER2-positive cancer is a particularly aggressive form of breast cancer.

About Genentech Access Solutions

Genentech is committed to people having access to our medicines. Genentech Access Solutions is a team of more than 350 Genentech employees who help those who need our medicines. Our knowledgeable and experienced Specialists can help patients and medical practices navigate the access and reimbursement process and provide assistance to eligible patients in the United States who do not have insurance coverage or who cannot afford their out-of-pocket co-pay costs. For more information, please visit http://www.Genentech-Access.com.

About Genentech

Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.