RAPT Therapeutics Halts Zelnecirnon Development After FDA Feedback and Liver Injury
核心洞察
RAPT Therapeutics discontinues the development of zelnecirnon, a CCR4 (搜索) antagonist, following regulatory feedback from the FDA and a case of liver failure (搜索) in trials.
The FDA had previously placed clinical holds on Phase IIb and Phase IIa trials of zelnecirnon for atopic dermatitis (搜索) and asthma (搜索) due to safety concerns.
Despite the setback, RAPT remains committed to its CCR4 (搜索) pipeline and seeks to identify a new drug candidate by early 2025.
RAPT Therapeutics has ceased the development of zelnecirnon, an investigational CCR4 (搜索) antagonist, after receiving discouraging feedback from the FDA. This decision follows a clinical hold placed on the drug's Phase IIb study for atopic dermatitis (搜索) and Phase IIa trial for asthma (搜索) in February 2024, triggered by a serious adverse event of liver failure (搜索) potentially linked to zelnecirnon.
Regulatory Hurdles and Safety Concerns
The specific feedback from the FDA remains undisclosed, but RAPT's president and CEO, Brian Wong, stated that the company does not see a viable path forward for zelnecirnon. The clinical hold was initiated after a patient in the atopic dermatitis (搜索) study experienced liver failure (搜索), a serious adverse event that prompted further scrutiny of the drug's safety profile.
Zelnecirnon's Potential and Prior Data
Zelnecirnon, designed as an orally available small molecule, targets the CCR4 (搜索) chemokine receptor, which is expressed by helper T cells and involved in inflammatory processes. Previous Phase Ia/Ib data, published in November 2023, indicated that once-daily zelnecirnon improved the Eczema Area and Severity Index (EASI) score by 36.3% in patients with moderate to severe atopic dermatitis (搜索) after four weeks of treatment, compared to a 17% reduction in the placebo group. Furthermore, EASI scores continued to improve, reaching a 53.2% reduction six weeks into the study, which RAPT attributed to zelnecirnon's mechanism of action affecting upstream cytokines.
Future Plans for RAPT
Despite discontinuing zelnecirnon, RAPT intends to continue developing its CCR4 (搜索) pipeline assets, focusing on improved safety margins. The company aims to identify a new drug candidate in the first half of 2025 and is actively seeking in-licensing contracts for clinical-stage assets. This strategic shift comes after RAPT experienced a net loss of $58.2 million in the first half of the year and laid off 40% of its workforce in July 2024 to conserve cash resources. As of June 30, RAPT had $114.8 million in cash, cash equivalents, and marketable securities.
Market Reaction
The announcement led to a significant drop in RAPT's stock price, with shares falling by as much as 43% in premarket trading on Monday.