FDA approves sub-cutaneous formulation of trastuzumab and pertuzumab combination

July 14, 20200
FDA approves sub-cutaneous formulation of trastuzumab and pertuzumab combination

With a pandemic paralyzing the world, forcing millions to stay at home, the U.S. Food and Drug Administration’s (USFDA) Oncology Centre of Excellence has proactively accelerated approvals to protect the vulnerable sub-population of cancer patients. A critical development is the approval of Genentech’s (Roche’s subsidiary) Phesgo™ four months before the FDA goal date. Phesgo™ is a fixed-dose combination of Herceptin® (trastuzumab), Perjeta® (pertuzumab) and hyaluronidase to be administered subcutaneously in combination with chemotherapy and Docetaxal  to adult patients with early-stage HER-2 positive Breast Cancer and metastatic HER-2 positive Breast cancer, respectively. This approval represents a significant breakthrough for cancer patients worldwide, as it is converting a combination of biological drugs delivered as an infusion until now in the hospital setting to a subcutaneous injection that can be administered in the doctor’s office or even at home.

Patients will continue to be chosen by an FDA-approved companion diagnostic test to this drug combination used for HER2 positive breast cancer patients. Normally a sequential administration through intravenous (IV) infusion takes about 150 minutes for a loading dose of Perjeta and Herceptin and about 60 to 150 minutes for subsequent maintenance infusions.  Phesgo™, on the other hand takes 8 minutes for the first dose to be administered and 5 minutes for subsequent maintenance doses.

Phesgo™’s phase 2 studies PHaranceSCa demonstrated a whooping 85% patients preferring Phesgo™ SC over IV administration of Perjeta® and Herceptin® on basis of comfort of administration and steep decrease in administration time. Process of approval of Phesgo™ was supported by results from previous studies on IV trastuzumab and pertuzumab as combination as well as the open-label, multicentre, randomized Phase 3 trial FeDeriCa for efficacy and safety that demonstrated non-inferiority of Phesgo™ SC over IV pertuzumab and trastuzumab.

Roche’s major revenue magnet, Herceptin (trastuzumab) recently lost its patent exclusivity opening market for biosimilars by companies like Amgen, Celltrion, Mylan, Cephalon, Bgp Pharma, Pfizer and Merck. In December 2017, Ogiviri (trastuzumab-dkst) by Mylan became the first biosimilar for treatment of breast and stomach cancer to be approved by FDA. While Pertuzumab patents expire in Europe in March 2023 and in US in June 2024, several global companies are engaged in early development of a biosimilar. Thus, Phesgo™ is also an important development for lifecycle management for Roche/Genentech’s portfolio of drugs for HER-2 positive breast cancer patients.  In March 2019, Genentech obtained FDA approval for Herceptin Hylecta, a subcutaneous formation of trastuzumab.  However, the current approval is Genentech’s first time combining two monoclonal antibodies to be subcutaneously administered, and a substantial milestone in biologic formulations.

20% of Breast cancer patients suffer from HER-2 positive breast cancer. In addition to trastuzumab biosimilars, the market for HER-2 positive breast cancer has been rife with treatment modalities leaning towards novel therapies such as antibody-drug conjugates (ADC) that are monoclonal antibodies linked with cytotoxic chemo drugs. Roche’s Kadycla is the first ADC targeting HER-2 positive breast cancer and AstraZeneca and Daiichi Sankyo’s Enhertu aims to compete Kadycla’s therapy. This April saw approval by FDA of a HER-2 positive breast cancer Kinase inhibitor, Tukysa by Seattle Genetics which will face market competition with the February approved kinase inhibitor Nerlynx by Puma Biotechnology.

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