FDA Accepts Biologics License Application for [Vic-]Trastuzumab Duocarmazine, an Antibody Drug Conjugate for HER2-Positive Metastatic Breast Cancer

The FDA has accepted a Biologics License Application (BLA) for [vic-]trastuzumab duocarmazine (SYD985) in patients with human estrogen receptor 2 (HER2)-positive unresectable locally advanced or metastatic breast cancer.

The license application was submitted by Byondis B.V., an independent Dutch clinical stage biopharmaceutical company. The FDA has given the company a Prescription Drug User Fee Act action date of May 12, 2023.

SYD985, an investigational next generation anti-HER2 antibody-drug conjugate (ADC), was granted fast track designation by the FDA in January 2018. The designation was granted based on phase 1 data involving heavily pretreated last-line HER2-positive metastatic breast cancer (MBC) patients.

“Women with HER2-positive breast cancer generally have a more aggressive disease, greater likelihood of recurrence and poorer prognosis,” said Byondis Chief Medical Officer Jan Schellens, MD, PhD, in a statement. “Today's SYD985 BLA acceptance by the FDA is an important step forward toward our goal of providing a much-needed alternative for these patients.”

This is the first regulatory submission for SYD985 from Byondis. The company supported the submission for BLA with data from their phase 3 TULIP multi-center, open-label, randomized clinical trial comparing SYD985 to physician's choice treatment in patients with pre-treated HER2-positive unresectable locally advanced or MBC.

Results of this study were presented at the 2021 ESMO Congress. The study met its primary end point of progression-free survival, demonstrating a statistically significant improvement of 2.1 months over the physician’s choice treatment as well as supportive overall survival results.

SYD985 is considered a form of targeted therapy. It incorporates Byondis’ proprietary duocarmazine linker-drug technology and the ADC, which is comprised of the anti-HER2 monoclonal antibody trastuzumab and a cleavable linker-drug.

Byondis explained that the antibody part of trastuzumab duocarmazine binds to HER2 on the surface of the cancer cell while the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced. The result is tumor cell death.

"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, PhD, in a press release. "SYD985 combines a HER2-targeting antibody with a novel and potent cytotoxic drug in a way that limits damage to healthy tissue."

The company hopes that SYD985 will improve treatment outcomes for patients with HER2-positive unresectable locally advanced or MBC.

Reference

FDA accepts Byondis’ Biologics license application for [Vic-]trastuzumab duocarmazine (SYD985) in HER2-positive metastatic breast cancer [press release]. Nijmegen, Netherlands: Byondis B.V.; July 12, 2022. https://www.prnewswire.com/news-releases/fda-accepts-byondis-biologics-license-application-for-vic--trastuzumab-duocarmazine-syd985-in-her2-positive-metastatic-breast-cancer-301584658.html. Accessed July 13, 2022.