Pfizer, Arvinas to Develop Protein Degrader for Breast Cancer

Pfizer and Arvinas recently entered into a global collaboration to develop and commercialize an investigation oral PROteolysis Targeting Chimera (PROTAC) estrogen receptor (ER) protein degrader for breast cancer.

The PROTAC protein degrader, ARV-471, is currently in Phase 2 dose expansion clinical trial for the treatment of patients with ER positive/ human epidermal growth factor receptor 2 (HER2), negative locally advanced or metastatic breast cancer. 

Pfizer and Arvinas are looking to develop ARV-471 as the potential endocrine therapy of choice for patients and their physicians.

“We are excited to work with Arvinas to maximize ARV-471, the first PROTAC for breast cancer with encouraging early clinical data and a potential novel hormonal therapy backbone for HR+ breast cancer,” Jeff Settleman, PhD, chief scientific officer for oncology research and development at Pfizer, said in the announcement. 

“This partnership complements Pfizer’s robust research activities in breast cancer, including our multiple next-generation CDK inhibitors currently in early clinical development,” Settleman continued. 

ER is the primary driver of hormone receptor positive breast cancer, which is the most common breast cancer subtype, a Pfizer spokesperson explained. 

And endocrine therapy is the foundation of ER and breast cancer treatment. It is used as a monotherapy or as combination therapy as a standard of care across various treatment settings.

The ongoing Phase 1 dose escalation clinical trial of ARV-471 enrolled heavily pretreated patients with locally advanced or metastatic ER/ HER2 breast cancer. All patients received prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors.

Data from December 2020 showed that ARV-471 had potential as a novel oral ER targeted therapy, could promote substantial ER degradation, and showed an encouraging clinical efficacy and tolerability profile. 

“This collaboration should significantly enhance and accelerate the development and potential commercialization of ARV-471,” said John Houston, PhD, chief executive officer at Arvinas. 

“We share Pfizer’s deep commitment to people with breast cancer and are thrilled to partner with them to develop this potentially best-in-class therapy. Despite advancements in oncology in recent years, considerable unmet need persists in the treatment of HR+ breast cancer,” Houston continued. 

Under terms of agreement, Pfizer will pay Arvinas $650 million upfront. Pfizer will also make a $350 million equity investment in Arvinas. 

ARV-471 is wholly owned by Arvinas, but the companies will equally share global development costs, commercialization expenses, and profits.

ARV-471 is also being evaluated in a Phase 2 monotherapy dose expansion study, VERITAC. Pfizer and Arvinas will initiate two additional trials of ARV-471 in 2021. And in 2022, the companies will initiate Phase 3 studies across lines of therapy in metastatic breast cancer.