FDA halts trial of BioNTech-MediLink ADC over 'significant risk of illness'

The FDA has slammed the brakes on a trial of MediLink Therapeutics’ BioNTech-partnered antibody-drug conjugate (ADC) that has already seen three fatalities, with the agency citing a risk of “unreasonable and significant risk of illness or injuries.”

The German drugmaker announced in a Securities and Exchange Commission filing this morning that the FDA has placed a phase 1 trial on partial hold over concerns that BNT326/YL202 “may, at higher doses, expose human subjects to unreasonable and significant risk of illness or injuries.”

A slide from BioNTech's presentation at the American Society of Clinical Oncology (ASCO) annual meeting three weeks ago showed that of 54 patients who had received BNT326/YL202 in the phase 1 trial as of Feb. 4., two patients from the fifth dose cohort had died, as well as one in the seventh dose group.

To address the FDA requests, MediLink needs to review the clinical and safety data for BNT326/YL202, BioNTech said in today's filing. This includes “providing additional information in the investigators brochure regarding the safety findings including grade 5 adverse events observed” in both the phase 1 study as well as a phase 2 trial of the ADC which, according to ClinicalTrials.gov, kicked off at the end of last year.

A grade 5 adverse event signifies a fatality. Fierce Biotech has reached out to BioNTech for more details about the grade 5 events in the trial.

“MediLink has taken actions to pause enrollment of new patients in the U.S. and address the FDA requirements,” BioNTech said.

In the ASCO slides, BioNTech said "further clinical development will focus on dose levels below 4.0 mg/kg, where the safety profile was manageable and promising clinical activity was observed."

Suzhou, China-based MediLink has been testing the HER3-targeting ADC in non-small cell lung cancer and breast cancer since late 2022, building on preclinical evidence that the ADC delivers its cytotoxic payload to tumor cells that express HER3 without causing significant toxicity to healthy tissues. 

In October 2023, BioNTech hopped on board, paying $70 million upfront for the rights to the asset beyond China in a deal that had $1 billion in biobucks attached.

At ASCO, MediLink and BioNTech presented data that showed that the overall response range for patients who received the third, fourth and fifth dose options was 41%.

The safety profile of the study at that point “showed adequate safety and tolerability,” they said in the abstract. Twenty percent of patients experienced anemia that was grade 3 or above, while 29% of patients saw a drop in neutrophil count that was grade 3 or higher.

There was one instance of a dose-limiting toxicity—grade 3 febrile neutropenia, which occurred at the highest dose.

BNT326/YL202 was created by MediLink’s solid-tumor-focused TMALIN ADC platform, and BioNTech’s interest in the platform isn’t limited to the one asset. In May, the German company handed over $25 million upfront for the chance to apply the TMALIN platform to several undisclosed targets.