Rapt Therapeutics faces a daunting challenge as the U.S. Food and Drug Administration (FDA) enforces a clinical hold on two significant trials of its drug candidates aimed at addressing eczema and asthma. This regulatory intervention follows a troubling development wherein a participant in one of the trials suffered from liver failure, causing reverberations within the company and the wider pharmaceutical sphere.
CEO Brian Wong, M.D., Ph.D., responded to the unfolding crisis by characterizing the situation as “regrettable and unforeseen” in a press release issued on Tuesday. Wong reiterated the company’s steadfast commitment to patient safety and pledged full cooperation with the FDA to expedite the resolution of the issue. The gravity of the adverse event cannot be overstated, particularly given its potential link to Rapt’s investigational drug, zelnecirnon.
The pivotal incident transpired during a phase 2b trial concentrated on atopic dermatitis, a prevalent inflammatory skin condition. The FDA’s decision to suspend this trial, along with a phase 2a study directed at asthma, underscores the seriousness of the situation and underscores the necessity for a thorough investigation. Rapt emphasized that prior to this occurrence, over 350 patients had received zelnecirnon across three trials without any reported instances of liver toxicity. Furthermore, phase 1 data released by the company affirmed the drug’s favorable safety profile, with no serious adverse effects documented.
The individual patient’s case introduces a multitude of potential contributing factors amid the complexity of drug development. Notably, the patient had a confirmed allergy to Dupixent, a drug commonly prescribed for inflammatory conditions such as eczema. Additionally, the patient was undergoing thyroid hormone replacement therapy for Hashimoto’s disease, an autoimmune disorder. The situation was further complicated by the patient contracting COVID-19 during the trial, adding another layer of complexity. Moreover, the use of ashwagandha, an herbal supplement linked to liver complications, adds additional intricacies to the case.
Investor confidence plummeted sharply in response to the news, with Rapt’s stock plummeting by 64% subsequent to the announcement of the clinical hold. This significant decline underscores the severity of the situation and highlights the substantial financial ramifications for the company. Rapt had previously anticipated disclosing interim data from its atopic dermatitis trial by mid-year, but the clinical hold has cast uncertainty over these projections.
As Rapt navigates this unprecedented challenge, all eyes are on its oncology program, particularly its phase 2 trials of tivumecirnon, a promising candidate being evaluated alone and in combination with Keytruda. With $184.8 million in cash reserves as of September, the company remains financially stable for the time being, but the resolution of the clinical hold will undoubtedly influence its future trajectory.
In response to the FDA’s directive, Rapt has taken decisive action, halting dosing for ongoing patients and suspending enrollment of new participants as it conducts a thorough investigation into the root cause of the adverse event. Analysts caution that this setback could result in significant delays in Rapt’s clinical development timelines, posing challenges for the company’s long-term growth prospects.
