South San Francisco, CA -- June 29, 2020 -- 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 Phesgo, a fixed-dose combination (FDC) of Perjeta® (pertuzumab) and Herceptin® (trastuzumab) with hyaluronidase, administered by subcutaneous (SC, under the skin) injection in combination with intravenous (IV) chemotherapy, for the treatment of early and metastatic HER2-positive breast cancer. This is the first time that Genentech has combined two monoclonal antibodies that can be administered by a single SC injection.

"The FDA approval of Phesgo reflects our commitment to improving outcomes for the many people living with HER2-positive breast cancer," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "Phesgo offers a treatment administration that supports the needs and preferences of individual patients, and helps to meet the increasing demand across the healthcare system for faster and more flexible treatment options."

Phesgo is available in one single-dose vial. Administration can take approximately eight minutes for the initial loading dose and approximately five minutes for each subsequent maintenance dose. This is compared to approximately 150 minutes for infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions of the two medicines. Phesgo can be administered by a healthcare professional in a treatment center or at a patient’s home.

The approval is based on results from the pivotal Phase III FeDeriCa study, which met its primary endpoint with Phesgo showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough) when compared to IV administration of Perjeta. The safety profile of Phesgo with chemotherapy was comparable to IV administration of Perjeta plus Herceptin and chemotherapy, and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhea and anemia.

The Phase II PHranceSCa study showed that 85% (136/160) of people receiving treatment for HER2-positive breast cancer preferred treatment under the skin to IV administration due to less time in the clinic and more comfortable treatment administration.

For those who qualify, Genentech will offer patient assistance programs for people prescribed Phesgo by their doctor through Genentech Access Solutions. Please contact Genentech Access Solutions at (866) 422-2377 or visit http://www.Genentech-Access.com for more information.

About the FeDeriCa study

FeDeriCa is an international, multi-center, two-arm, randomized, open-label, Phase III study evaluating the pharmacokinetics, efficacy, and safety of SC injection of Phesgo in combination with chemotherapy, compared with standard IV infusion of Perjeta and Herceptin in combination with chemotherapy, in 500 people with HER2-positive EBC who are being treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings. The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough). Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and total pathological complete response, meaning there is no tumor tissue detectable in the tissue removed at the time of surgery. The safety profile of Phesgo was comparable with that of Perjeta and Herceptin administered intravenously.

Data from the FeDeriCa study were presented at the San Antonio Breast Cancer Symposium in December 2019. The FeDeriCa study met its primary endpoint of non-inferior levels of Perjeta in the blood. The geometric mean ratio (GMR; a type of average used when assessing pharmacokinetics) for the primary endpoint was 1.22 (90% CI: 1.14 to 1.31), with the lower limit of the 90% CI of the GMR=1.14≥0.80 (the pre-specified non-inferiority margin). A secondary endpoint of non-inferior levels of Herceptin was also met, with blood concentrations for people receiving the fixed-dose combination non-inferior to those receiving IV Herceptin (GMR=1.33 [90% CI: 1.24 to 1.43]; lower limit of 90% CI of GMR=1.24≥0.80). A non-inferiority endpoint was chosen for the study to ensure that people were receiving sufficient dosing with Perjeta and Herceptin as compared to the established IV doses at the same treatment intervals.

About the PHranceSCa study

PHranceSCa is a randomized, multi-center, multinational, open-label, cross-over Phase II study evaluating patient preference for and satisfaction with subcutaneous (SC) administration of Phesgo. All patients completed neoadjuvant treatment with Perjeta, Herceptin and chemotherapy and had surgery before randomization. The primary endpoint of the study is the percentage of participants who indicate that they prefer treatment with Phesgo compared to the standard intravenous (IV) formulations of Perjeta and Herceptin. Secondary endpoints include participant-reported satisfaction and health-related quality of life outcomes; healthcare professionals' perceptions of time and resource use and convenience compared with IV formulations; as well as the safety and efficacy of each study regimen.

About HER2-positive breast cancer

Breast cancer is one of the most common cancers among women worldwide. According to the American Cancer Society, close to 280,000 people in the United States will be diagnosed with breast cancer, and more than 42,000 will die from the disease in 2020. 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% of breast cancers are HER2-positive based on the result of a diagnostic test.

About Phesgo

Phesgo (subcutaneous Perjeta and Herceptin) is a new fixed-dose formulation of Perjeta and Herceptin with Halozyme Therapeutics’ Enhanze® drug delivery technology.

Trastuzumab in Phesgo is the same monoclonal antibody as in IV Herceptin and pertuzumab in Phesgo is the same monoclonal antibody as in IV Perjeta. 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.

Halozyme’s Enhanze drug delivery technology may enable and optimize SC drug delivery for appropriate co-administered therapeutics. The technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body, to aid in the dispersion and absorption of other injected therapeutic drugs.

Phesgo Indications and Important Safety Information

Phesgo (pertuzumab, trastuzumab, and hyaluronidase-zzxf) is a prescription medicine approved for use in combination with chemotherapy for:

• use prior to surgery (neoadjuvant treatment) in adults with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (tumor is greater than 2 cm in diameter or node-positive). Phesgo should be used as part of a complete treatment regimen for early breast cancer.
• use after surgery (adjuvant treatment) in adults with HER2-positive early breast cancer that has a high likelihood of coming back.
• Phesgo is also approved for use in combination with docetaxel in adults 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.

Important Safety Information

What should patients know about side effects with Phesgo?

• Not all people have serious side effects; however, side effects with Phesgo therapy are common. It is important to know what side effects may happen and what symptoms to watch for
• A patient’s doctor may stop treatment if serious side effects happen. Patients 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 with Phesgo

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

• The risk for and seriousness of these heart problems are highest in people who received both Phesgo and a certain type of chemotherapy (anthracycline)
•  A patient’s doctor will check for signs of heart problems before, during, and after treatment with Phesgo. Based on test results, their doctor may hold or discontinue treatment with Phesgo
• Patients should contact their healthcare professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness

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

• Birth control should be used while receiving Phesgo and for 7 months after the last dose of Phesgo. If a patient is a mother who is breastfeeding, she should talk with her doctor about either stopping breastfeeding or stopping Phesgo
• If the patient thinks she may be pregnant, she should contact her healthcare provider immediately
• If the patient is exposed to Phesgo during pregnancy, or becomes pregnant while receiving Phesgo or within 7 months following the last dose of Phesgo, she is encouraged to report Phesgo exposure to Genentech at 1-888-835-2555

Phesgo may cause serious lung problems.

• A patient’s doctor may check for signs of lung problems including:
  • Severe shortness of breath
  • Fluid in or around the lungs
  • Weakening of the valve between the heart and the lungs
  • Not enough oxygen in the body
  • Swelling of the lungs
  • Scarring of the lungs

Who should not receive Phesgo?

• Phesgo should not be used in patients who are allergic to pertuzumab, trastuzumab, hyaluronidase, or to any of the ingredients in Phesgo

Other possible serious side effects

• Phesgo may worsen low white blood cell counts caused by chemotherapy : Low white blood cell counts can be life threatening and were seen more often in patients receiving Herceptin® (trastuzumab) plus chemotherapy than in patients receiving chemotherapy alone. A patient’s doctor may check for signs of low white blood cell counts when he or she examines the patient
• Phesgo may cause administration-related reactions: Phesgo is given as an injection. The active ingredients in Phesgo have been associated with severe administration reactions, including hypersensitivity or anaphylaxis, which can be fatal. Patients should talk to their doctor if they feel any symptoms. The most common symptoms include dizziness, nausea, chills, fever, vomiting, diarrhea, hives, swelling of the skin, breathing problems, or chest pain

Most common side effects

The most common side effects of Phesgo when given with chemotherapy as part of an early breast cancer regimen are:

• Hair Loss
• Nausea
• Diarrhea
• Low levels of red blood cells
• Weakness

The most common side effects of Phesgo when given with docetaxel for treatment of breast cancer that has spread to other parts of the body (metastatic) are:

• Diarrhea
• Hair loss
• Low levels of white blood cells with or without fever
• Nausea
• Feeling tired
• Rash
• Damage to the nerves (numbness, tingling, pain in hands/feet)

Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.

Patients should talk to a healthcare professional for more information about the benefits and risks of Phesgo.

Please see full Prescribing Information for additional Important Safety Information, including most serious side effects.

If a patient cannot afford their medication, visit http://www. genentech-access.com/patient for financial assistance information.

About Expanded Access Treatment Protocol for Continuity of Care During COVID-19

Genentech launched an expanded access treatment protocol in the United States, where the FDC of Perjeta and Herceptin is administered at home by a home health nursing provider. The study will continue beyond approval, aiming to help continuity of care during the COVID-19 pandemic for certain patients with HER2-positive breast cancer who have completed chemotherapy concurrent with Perjeta and Herceptin intravenously and are currently receiving or will be receiving Perjeta and Herceptin alone. To learn more, please visit here .

About Genentech Access Solutions

Access Solutions is part of Genentech’s commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process, and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine. To date, the team has helped more than 2 million patients access the medicines they need. Please contact Access Solutions (866) 4ACCESS/(866) 422-2377 or visit http://www.Genentech-Access.com for more information.

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.

Source: Genentech

Posted: June 2020