In June, the regulator placed a partial clinical hold on a Phase I trial of the companies’ antibody-drug conjugate after three patient deaths were reported.
The FDA has lifted a partial clinical hold on BioNTech and China-based MediLink Therapeutic’s antibody-drug conjugate after the Phase I trial’s procedures were amended, the German company announced Monday.
BioNTech and MediLink’s HER3-targeting antibody-drug conjugate (ADC), BNT326/YL202, is currently in Phase I and being investigated for treating non-small cell lung and breast cancer. In June, the FDA placed a partial clinical hold on the ADC’s trial after multiple patient deaths were reported, as well as a “significant” risk of illness or injuries.
“The complete response including data analysis, updated investigator brochure and informed consent for patients, and amended clinical trial protocol meets the FDA’s requirements by incorporating additional risk mitigation measures,” BioNTech said in its announcement.
While the specifics of the changes were not disclosed, BioNTech announced that trial recruitment will be re-initiated and development “will focus on dose levels no higher than 3 mg/kg, where the safety profile was manageable and encouraging clinical activity was observed.
Bank of Montreal Capital Markets analyst Etzer Darout in a note to investors said the 3 mg/kg dosing amount “showed encouraging efficacy” with 10 patients treated achieving a 60% overall response rate and 100% disease control rate, as well as a tolerable safety profile.
However, one of the catalysts for the clinical hold was the observation of a neutrophil count decrease, known as neutropenia, and an increase in mucositis events. BioNTech said that these events are common adverse events of chemotherapy and can increase a patient’s risk of developing a severe infection. The limiting of the dosing amount should help reduce neutropenia, according to Monday’s announcement.
Darout wrote that the FDA’s lifting of the partial clinical hold is an “incremental positive” for BioNTech and its ADC programs.
MediLink and BioNTech inked a strategic collaboration and licensing agreement in October 2023 to develop ADCs to target cancer. Under the deal, BioNTech made an upfront payment of $70 million and offered more than $1 billion in potential development and commercial milestones. The company has rights to market the ADCs globally outside of the Greater China region, which will remain MediLink’s territory.
The FDA’s lifting of the partial hold comes as BioNTech has been struggling financially. The company reported in its second-quarter 2024 earnings a loss of more than $850 million, a fourfold increase from the $208 million reported in Q2 2023. This was due to continued falloff in sales of its COVID-19 products as well as an increase in R&D investment.
