New HER2 Drug for Breast Cancer Stalled by FDA

M. Alexander Otto, PA, MMS

May 16, 2023

A new drug for breast cancer that was approaching the market in the United States has been stalled: Trastuzumab duocarmazine (developed by Byondis) was awaiting approval for use in HER2-positive unresectable locally advanced or metastatic breast cancer.

However, the US Food and Drug Administration (FDA) said that it needs more data and for now "suspends the decision on the product's approvability," the manufacturer announced on May 15.

Byondis said that it is "disappointed with this outcome" but remains optimistic about the drug's potential. "We continue to believe" that the product offers "a meaningful treatment option for patients living with HER2-positive metastatic breast cancer," commented Byondis CEO Marco Timmers, PhD.

The company will now evaluate the FDA's response and consider next steps. The product is awaiting approval in the European Union and the United Kingdom.

An Improvement?

Trastuzumab duocarmazine is an antibody-drug conjugate (ADC) composed of a monoclonal antibody that homes in on HER2 to deliver a cytotoxic agent.

There are already two ADCs on the market: trastuzumab deruxtecan (Enhertu) and trastuzumab emtansine (Kadcyla).

Byondis claims that its product improvement on what's come before. "While earlier generation ADCs improved targeting and cell killing, they were unstable in the bloodstream, leading to premature release of the cytotoxic payload, impacting healthy tissue and narrowing the therapeutic window," the company said in a 2022 press release.

Trastuzumab duocarmazine, on the other hand, is "highly stable in circulation and carr[ies] an intricate, inactivated and potent cytotoxic drug that rapidly self-destructs if it is prematurely released, limiting damage to healthy tissue and improving the therapeutic window," Byondis said.

The novel mechanism of action means that trastuzumab duocarmazine will remain effective "when other ADC therapies have been exhausted," said the Timmers in the press release, which was issued last year when the company submitted its application for FDA approval.

That application was based on data from the TULIP trial, which included 437 women with locally advanced or metastatic HER2-positive breast cancer who had received at least two prior treatments for metastatic disease or who had progressed on trastuzumab emtansine.

Participants were randomized in a 2:1 ratio to receive trastuzumab duocarmazine or physician's choice of lapatinib plus capecitabine, trastuzumab plus capecitabine, trastuzumab plus vinorelbine, or trastuzumab plus eribulin, given until intolerable toxicity or disease progression.

Median progression-free survival was 7 months with trastuzumab duocarmazine vs 4.9 months in the control group (hazard ratio [HR], 0.64; P = .002). There was a trend toward improved overall survival (HR, 0.83; P = .153) but no significant differences in objective response rates or healthcare-related quality-of-life scores.

Overall, 35.4% of patients discontinued trastuzumab duocarmazine owing to adverse events, including eye disorders (20.8%) and respiratory disorders (6.3%).

The most frequently reported adverse events were conjunctivitis (38.2%), keratitis (38.2%), and fatigue (33.3%); 7.6% of patients developed interstitial lung disease/pneumonitis. Two died of the complication.

M. Alexander Otto is a physician assistant with a master's degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email:

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