Monday, Feb 4, 2019

Genentech Submits Supplemental Biologics License Application to FDA For Kadcyla for Adjuvant Treatment of People With HER2-Positive Early Breast Cancer With Residual Disease After Neoadjuvant Treatment

Application is being reviewed under FDA's Real-Time Oncology Review and Assessment Aid pilot programs 

Kadcyla was granted Breakthrough Therapy Designation for this application

South San Francisco, CA -- February 4, 2019 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced completing the submission of a supplemental Biologics License Application to the U.S. Food and Drug Administration (FDA) for Kadcyla ^® (ado-trastuzumab emtansine) for adjuvant (after surgery) treatment of people with HER2-positive early breast cancer (EBC) with residual disease after neoadjuvant (before surgery) treatment. The FDA is reviewing the application under the Real-Time Oncology Review and Assessment Aid pilot programs, which aim to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. For this indication, Kadcyla was also granted Breakthrough Therapy Designation, which is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases.

“Kadcyla was granted Breakthrough Therapy Designation and is also the first Genentech medicine to be reviewed under the FDA’s Real-Time Oncology Review pilot program; both FDA initiatives aim to expedite reviews and bring medicines to patients sooner,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are working closely with the FDA to bring Kadcyla to people with HER2-positive early breast cancer who have residual disease after neoadjuvant therapy as early as possible.”

This application is based on results of the Phase III KATHERINE study showing Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival; iDFS) by 50 percent (HR=0.50, 95% CI 0.39-0.64, p<0.0001) compared to Herceptin^® (trastuzumab) as an adjuvant treatment in people with HER2-positive EBC who have residual disease present following neoadjuvant treatment. People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease. At three years, 88.3 percent of people treated with Kadcyla did not have their breast cancer return compared to 77.0 percent treated with Herceptin, an absolute improvement of 11.3 percent.

The most common Grade 3-4 side effects (≥1 percent) with Kadcyla in the KATHERINE study were decreased platelet count; high blood pressure; radiation-induced skin injury; numbness, tingling or pain in the hands or feet; decreased neutrophil count; low blood potassium level; fatigue and decrease in red blood cells.

About the KATHERINE study

KATHERINE is an international, multi-center, two-arm, randomized, open-label, Phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive EBC who have pathological invasive residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy that included Herceptin and taxane-based chemotherapy. The primary endpoint of the study is iDFS, which in this study is defined as the time from randomization free from invasive breast cancer recurrence or death from any cause. Secondary endpoints include disease-free survival and overall survival.

About HER2-positive breast cancer 

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 271,000 people in the United States will be diagnosed with breast cancer, and more than 42,000 will die from the disease in 2019. Breast cancer is not one, but many diseases based on the biology of each tumor. In HER2-positive breast cancer, there is excess HER2 protein on the surface of tumor cells. Approximately 15-20 percent of breast cancers are HER2-positive based on the result of a diagnostic test.

About Kadcyla

Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cells. It is designed to limit damage to healthy tissues, although it can still affect them. Kadcyla can cause serious side effects. It combines two anti-cancer agents using a stable linker: the HER2-targeting trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1. Kadcyla is the only ADC approved for the treatment of HER2-positive metastatic breast cancer. In the U.S., Genentech licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

Kadcyla Indication Statement

Kadcyla, as a single agent, is indicated for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:

• Received prior therapy for metastatic disease, or
• Developed disease recurrence during or within six months of completing adjuvant therapy.

Important Safety Information

Most important safety information about Kadcyla

Kadcyla is not the same medicine as trastuzumab (Herceptin). 

Liver problems

• Kadcyla may cause severe liver problems that can be life-threatening. Symptoms of liver problems may include vomiting, nausea, eating disorder (anorexia), yellowing of the skin (jaundice), 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, rapid weight gain of more than five pounds in 24 hours, dizziness or loss of consciousness, or irregular heartbeat.

Pregnancy

• Receiving Kadcyla during pregnancy can result in the death of an unborn baby and birth defects. Birth control should be used while receiving Kadcyla and for seven months after a patient’s last dose of Kadcyla.
• If a patient thinks she may be pregnant, she should contact her healthcare provider immediately.
• If a patient is exposed to Kadcyla during pregnancy, or becomes pregnant within seven months following her last dose of Kadcyla, she is encouraged to report Kadcyla exposure to Genentech at (888) 835-2555.
• If a male patient has a female partner that could become pregnant, birth control should be used during treatment and for four months following his last dose of Kadcyla.
• A patient should not breastfeed during treatment and for seven months after the last dose of Kadcyla.
  

A patient should contact their doctor right away if they experience symptoms associated with these side effects. 

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. A patient’s doctor will monitor the patient for infusion-related reactions.

Serious bleeding

• Kadcyla can cause life-threatening bleeding. Taking Kadcyla with other medications used to thin the blood (antiplatelet) or prevent blood clots (anticoagulation) can increase the risk of bleeding. A patient’s doctor should provide additional monitoring if the patient is taking one of these other drugs while on Kadcyla. Life-threatening bleeding may also happen with Kadcyla, even when blood thinners are not also being taken.

Low platelet count

• Low platelet count may happen during treatment with Kadcyla. Platelets help the blood to clot. Signs of low platelets may include easy bruising, bleeding, and prolonged bleeding from cuts. In mild cases there may not be any symptoms.

Nerve damage

• Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, 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 

A patient must have a HER2 test to determine if their breast cancer is HER2-positive before taking Kadcyla, because benefit has been shown only in patients whose tumors are HER2-positive.
Most common side effects of Kadcyla

The most common side effects seen in people taking Kadcyla are:

• Tiredness
• Nausea
• Pain that affects the bones, muscles, ligaments and tendons
• Bleeding
• Low platelet count
• Headache
• Liver problems
• Constipation
• Nosebleeds

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

Please see the Kadcyla full Prescribing Information for additional Important Safety Information, including most serious side effects, at http://www.kadcyla.com. 

About Genentech in breast cancer 

Genentech has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have substantially improved outcomes for HER2-positive breast cancer. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including triple-negative and hormone receptor-positive.

About Genentech
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and 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.

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