FDA Accepts BLA for Advanced HER2 Breast Cancer Therapy


The FDA has assigned a Prescription Drug User Fee Act action date of May 12, 2023, for [vic-]trastuzumab duocarmazine (SYD985).

The FDA has accepted Byondis’ biologics license application (BLA) for [vic-]trastuzumab duocarmazine (SYD985) in patients with HER2-positive unresectable locally advanced or metastatic breast cancer. The agency has assigned a Prescription Drug User Fee Act (PDUFA) action date of May 12, 2023.

The application is supported by data from the pivotal phase 3 TULIP clinical trial comparing SYD985 with physician’s choice treatment in patients with pre-treated HER2-positive metastatic breast cancer. The study enrolled 437 women with a median of four prior treatments.

The study’s primary endpoint median progression-free survival was 7.0 months for SYD985 and 4.9 months for physician’s choice. A first analysis of overall survival indicated the hazard ration was 0.83. (A hazard ratio over 1 indicates risk of harm when compared with the control.) There were no significant differences in objective response rate or health-related quality of life.

The most frequently reported adverse events for SYD985 were conjunctivitis, keratitis and fatigue. These results were first reported at the September 2021 meeting of the European Society for Medical Oncology.

Marco Timmers, Ph.D.

Marco Timmers, Ph.D.

“With our proprietary technologies, we aim to offer antibody-drug conjugates with a novel mechanism-of-action, which are still efficacious when other ADC therapies have been exhausted,” said Byondis CEO Marco Timmers, Ph.D. “SYD985 combines a HER2-targeting antibody with a novel and potent cytotoxic drug in a way that limits damage to healthy tissue.”

Women with HER2-positive breast cancer have a more aggressive disease, greater likelihood of recurrence and poorer prognosis, compared with women with HER2-negative breast cancer. About 20% of all breast cancers are HER2-positive, with younger women being the most affected

Trastuzumab was first approved by the FDA in 1998 as Herceptin. Developed by Genentech, the monoclonal antibody was a breakthrough therapy that specifically targeted HER2 alterations. Since 2017, five Herceptin biosimilars have been approved: Celltrion’ Herzuma, Amgen’s Kanjinti, Mylan’s Ogivri, Samsung Bioepis’ Ontruzant, and Pfizer’s Trazimera.

But some patients develop resistance, requiring additional therapy.

SYD985 is a next-generation antibody-drug conjugate (ADC). It adds Byondis’ duocarmazine linker-drug technology ByonZine to trastuzumab. This technology allows it to bind to minor groove of cancer DNA and disrupt the nucleic acid architecture, which eventually leads to tumor cell death.

The FDA granted fast track designation to SYD985 in January 2018 based on promising phase 1 data involving heavily pretreated last-line patients with HER2-positive metastatic breast cancer.

Byondis is conducting additional studies of SYD985, including a phase 2 clinical trial in HER2- metastatic endometrial cancer and a phase 2 study exploring the synergistic effects of [vic-]trastuzumab duocarmazine and niraparib in patients with HER2-expressing metastatic solid tumors. [Vic-]trastuzumab duocarmazine is also part of a new arm of the Quantum Leap Health Collaborative I-SPY 2 TRIAL investigating the neoadjuvant use of [vic-]trastuzumab duocarmazine in HER2-low early-stage breast cancer.

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