One of the most competitive fields in pharma today involves antibody drug conjugates (ADCs), a market estimated to be worth almost $20B already. This week the FDA accepted the supplemental Biologics License Application (sBLA) for ADC Enhertu (fam-trastuzumab deruxtecan-nxki) and granted it Priority Review. Enhertu is a HER2-directed ADC being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
Enhertu is particularly promising. In the summer of 2022, it became the first FDA approved drug for HER2-low breast cancer. It has more than 40 approvals worldwide for indications including breast cancer, lung cancer, and gastric cancer.
This FDA acceptance is a breakthrough, in that it covers patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumors who have received prior treatment or with no alternative treatment options.
ADCs combine the specificity of monoclonal antibodies with cytotoxic drugs, aimed at delivering highly targeted treatment. The field has momentum, and it doesn’t seem to be slowing. Among the bigger deals, in March of this year, Pfizer acquired ADC pioneer Seagen for $43 billion, a move that would double the big pharma’s early-stage oncology clinical pipeline. Also in December of this year, BMS signed an $8.4B ADC deal with SystImmune. Earlier, in October of this year, Merck inked a $4B deal with Daiichi.
“Biomarkers for HER2 expression are already established in breast and gastric cancers, but we must now define them across tumor types. We will continue working closely with the FDA to bring this potential first tumor-agnostic HER2-targeted medicine and biomarker to patients as quickly as possible,” Susan Galbraith, executive vice president, oncology R&D, AstraZeneca.
The sBLA is based on data from the ongoing DESTINY-PanTumor02 Phase II trial where ENHERTU demonstrated and durable responses leading to a clinically meaningful survival benefit in previously treated patients across HER2-expressing metastatic solid tumors, including biliary tract, bladder, cervical, endometrial, ovarian cancers, and other tumors. Data from other supporting trials in patients with HER2-positive IHC3+ tumors in the ENHERTU clinical development program, including DESTINY-Lung01 and DESTINY-CRC02, were also included in the submission.
Ken Takeshita, MD, global head, R&D, Daiichi Sankyo, said, “The clinical benefit seen across HER2-expressing metastatic solid tumors in the DESTINY-PanTumor02 trial and ongoing data from the ENHERTU clinical development program continues to demonstrate the potential of this medicine beyond its approved indications. If approved, ENHERTU could become the first HER2-directed therapy and antibody drug conjugate with a tumor-agnostic indication, providing patients with a potential new treatment option.”
The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) program and Project Orbis, two initiatives of the FDA which are designed to bring safe and effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application. Project Orbis provides a framework for concurrent submission and review of oncology medicines among participating international partners.