The FDA placed an early-stage BioNTech trial on partial clinical hold after researchers observed multiple deaths, the company said in an SEC filing Monday.
Regulators told BioNTech partner MediLink Therapeutics that an antibody-drug conjugate called BNT326/YL202 could expose patients to “unreasonable and significant risk” after deaths occurred in two separate studies, according to the filing. New patient enrollment has been paused in the US, and MediLink will need to review its data and update its investigator brochure about the deaths in order to lift the pause.
MediLink has begun taking steps to address the FDA’s concerns, the filing said.
The companies didn’t provide any detail about the deaths to the SEC, but BioNTech outlined safety data from a Phase 1 study at ASCO earlier this month. In a June 4 presentation, BioNTech said there were 14 total deaths during treatment, three of which resulted from drug-related side effects.
Two deaths occurred in a cohort testing the third-highest dose regimen (out of seven), BioNTech said. One patient died from sepsis/febrile neutropenia and the other from sepsis/pancytopenia. Both died roughly one month into treatment, according to the presentation.
The third patient who died was enrolled in the highest dose regimen, though their cause of death was unclear. The presentation mentioned interstitial pneumonia at the bottom in fine print, but did not link it to any specific patient.
On June 4, BioNTech summarized its safety findings from the trial by noting the signals seen were “consistent with its mechanism of action; an excess of hematologic toxicity, including fatal infections after febrile neutropenia, was identified at DL5 and above.” It also said further clinical development would focus on the dose levels below where toxicity was observed.
BioNTech updated its ASCO presentation on June 14, removing mention of the causes of death in fine print as well as the reference to “excess hematologic toxicity” seen at the higher doses. But the company also specified in the updated presentation that future development would center on doses below the third-highest regimen where it saw “promising clinical activity.”
BioNTech has signed two ADC partnership deals since October and promised up to $1.8 billion in biobucks. The Phase 1 study was testing BNT326/YL202, which targets HER3, in late-line settings for multiple solid tumors, including lung cancer and breast cancer.
A BioNTech spokesperson declined to comment beyond the SEC filing and the company’s previous public statements. MediLink could not be reached for comment.