Genentech’s Perjeta Nabs FDA Priority Review For Early Breast Cancer

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Perjeta^® (pertuzumab), in combination with Herceptin^® (trastuzumab) and chemotherapy (the Perjeta-based regimen), for adjuvant (after surgery) treatment of HER2-positive early breast cancer (EBC). The FDA is expected to make a decision on approval by January 28, 2018. The sBLA is based on results of the Phase III APHINITY study. A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

“We are pleased to receive Priority Review for the Perjeta-based regimen for the adjuvant treatment of HER2-positive early breast cancer”

“We are pleased to receive Priority Review for the Perjeta-based regimen for the adjuvant treatment of HER2-positive early breast cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “The goal of treating breast cancer early is to provide people with the best chance for a cure. Despite advances in the treatment of this disease, many people treated with the current standard of care still see their cancer return.”

The APHINITY study is part of our commitment to the FDA to evaluate the Perjeta-based regimen as part of a complete treatment approach for EBC. This sBLA seeks to convert the current accelerated approval to full approval. In the U.S., the combination of Perjeta, Herceptin and docetaxel chemotherapy is currently available under accelerated approval for neoadjuvant treatment of people with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than two centimeters in diameter or node-positive) as part of a complete treatment regimen for early breast cancer. Currently, no data have shown whether or not treatment with Perjeta prior to surgery improves survival. The safety of Perjeta in combination with doxorubicin-containing regimens has not been established. The safety of Perjeta administered for greater than six cycles for early-stage breast cancer has not been established.

Perjeta is also approved for use in combination with Herceptin and docetaxel for people who have HER2-positive breast cancer that has spread to different parts of the body (metastatic) and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer.

About APHINITY

APHINITY (Adjuvant Pertuzumab and Herceptin IN Initial TherapY in Breast Cancer, NCT01358877/ BO25126/ BIG 4-11) is an international, Phase III, randomized, double-blind, placebo-controlled, two-arm study evaluating the efficacy and safety of Perjeta plus Herceptin and chemotherapy compared to Herceptin and chemotherapy as adjuvant therapy in 4,805 people with operable HER2-positive EBC. The primary efficacy endpoint of the APHINITY study is invasive disease-free survival (iDFS), which in this study is defined as the time a patient lives without return of invasive breast cancer at any site or death from any cause after adjuvant treatment. Secondary endpoints include cardiac and overall safety, overall survival, disease-free survival and health-related quality of life.

APHINITY Study Results
Median follow-up for intent-to-treat (ITT) population 45.4 months (381 events)
Primary endpoint: invasive disease-free survival (iDFS)
HR=0.81; 95% CI 0.66-1.00, p=0.045
			Perjeta + Herceptin +			Placebo + Herceptin +
			chemotherapy			chemotherapy
			n=2,400			n=2,404
iDFS at 3 years
ITT population n=4,804			94.1% 171 events			93.2% 210 events
			HR=0.81; 95% CI 0.66-1.00, p=0.045
Node-positive subgroup n=3,005			92.0% 139 events			90.2% 181 events
			HR=0.77; 95% CI 0.62-0.96, p=0.019
Node-negative subgroup n=1,799			97.5% 32 events			98.4% 29 events
			HR=1.13; 95% CI 0.68-1.86, p=0.644
Hormone receptor-positive subgroup n=3,082			94.8% 100 events			94.4% 119 events
			HR=0.86; 95% CI 0.66-1.13, p=0.277
Hormone receptor-negative subgroup n=1,722			92.8% 71 events			91.2% 91 events
			HR=0.76; 95% CI 0.56-1.04, p=0.085
Estimate of iDFS at 4 years*
ITT population n=4,804			92.3%			90.6%
Node-positive subgroup n=3,005			89.9%			86.7%
Node-negative subgroup n=1,799			96.2%			96.7%
Hormone receptor-positive subgroup n=3,082			93.0%			91.6%
Hormone receptor-negative subgroup n=1,722			91.0%			88.7%
Safety
Grade 3 or higher adverse event (AE)			64.2%			57.3%
Fatal AE			0.8%			0.8%
Primary cardiac event**			0.7%			0.3%
			Difference 0.4%; 95% CI 0.0-0.8%
Most common (=5%) severe (Grade 3 or higher) AEs
Neutropenia Decrease in a certain type of white blood cell			16.3%			15.7%
Febrile neutropenia Fever associated with decrease in a certain type of white blood cell			12.1%			11.1%
Diarrhea			9.8%			3.7%
Diarrhea Onset after chemotherapy, during targeted therapy			0.5%			0.2%
Neutrophil count decreased Decrease in a certain type of white blood cell			9.6%			9.6%
Anemia Decrease in red blood cells or hemoglobin			6.9%			4.7%

* iDFS at four years was calculated based on data available at the time of primary analysis with median follow-up of 45.4 months

** Primary cardiac events included heart failure New York Heart Association (NYHA) class III or IV with left ventricular ejection fraction (LVEF) drop =10 points from baseline and to below 50 percent; and cardiac death

About Perjeta

Perjeta is a medicine that targets the HER2 receptor, a protein found on the outside of many normal cells and in high quantities on the outside of cancer cells in HER2-positive cancers. Perjeta is designed specifically to prevent the HER2 receptor from pairing (or ‘dimerizing’) with other HER receptors (EGFR/HER1, HER3 and HER4) on the surface of cells, a process that is believed to play a role in tumor growth and survival. Binding of Perjeta to HER2 may also signal the body’s immune system to destroy the cancer cells. The mechanisms of action of Perjeta and Herceptin are believed to complement each other, as both bind to the HER2 receptor, but to different places. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of HER signaling pathways, thus preventing tumor cell growth and survival.

Perjeta Indication Statements

Perjeta is approved for use in combination with Herceptin and docetaxel in people who have HER2-positive breast cancer that has spread to different parts of the body (metastatic) and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer.

Perjeta is approved for use prior to surgery in combination with Herceptin and docetaxel chemotherapy in people with HER2-positive, locally advanced, inflammatory, or early stage (tumor is greater than two centimeters in diameter or node-positive) breast cancer. Perjeta should be used as part of a complete treatment regimen for early stage breast cancer. This use of Perjeta is based on an improvement in the percentage of patients whose cancer shrinks or disappears after treatment. Currently, no data have shown whether or not treatment with Perjeta prior to surgery improves survival.

• The safety of Perjeta in combination with doxorubicin-containing regimens has not been established.
• The safety of Perjeta administered for greater than six cycles for early stage breast cancer has not been established.

Important Safety Information

Side effects with Perjeta

• Not all people have serious side effects; however, side effects with Perjeta therapy are common. It is important for a patient to know what side effects may happen and what symptoms a patient should watch for.
• A patient’s doctor may stop treatment if serious side effects happen. A patient should be sure to contact their healthcare team right away if they have questions or are worried about any side effects.

Most serious side effects

Perjeta may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure).

• A patient’s doctor may run tests to monitor the patient’s heart function before and during treatment with Perjeta.
• Based on test results, a patient’s doctor may hold or discontinue treatment with Perjeta.

Receiving Perjeta during pregnancy can result in the death of an unborn baby and birth defects.

• Birth control should be used while receiving Perjeta and for seven months after a patient’s last dose of Perjeta in combination with Herceptin. If a patient is a mother who is breastfeeding, the patient should talk with her doctor about either stopping breastfeeding or stopping Perjeta.
• If a patient thinks she may be pregnant, the patient should contact her healthcare provider immediately.
• If a patient is exposed to Perjeta during pregnancy, or becomes pregnant while receiving Perjeta or within seven months following the last dose of Perjeta in combination with Herceptin, the patient is encouraged to enroll in the MotHER Pregnancy Registry by contacting (800) 690-6720 or visiting http://www.motherpregnancyregistry.com, and to report Perjeta exposure to Genentech at (888) 835-2555.

Other possible serious side effects

• Perjeta should not be used in patients who are allergic to pertuzumab or to any of the ingredients in Perjeta.


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