RAPT ends Phase II trials for lead candidate after clinical hold

RAPT Therapeutics recently announced the termination of two Phase II clinical trials for its lead candidate, zelnecirnon (RPT193), following a clinical hold imposed by the US Food and Drug Administration (FDA) three months earlier. The FDA's decision to place a hold on the Phase IIa and Phase IIb trials was prompted by a serious adverse event—liver failure—in a patient participating in the atopic dermatitis study. Consequently, RAPT Therapeutics observed a significant decline in their stock value, dropping by 41.7% after the announcement and over 82% since the clinical hold was initially disclosed.

Despite the setback, RAPT Therapeutics is moving forward with data analysis from the trials, which included around 110 of the 229 patients who had completed the 16-week dosing in the atopic dermatitis study before the hold. The company believes that this data will be sufficient to inform future discussions with the FDA. According to Brian Wong, President and CEO of RAPT Therapeutics, the company is collaborating with clinical trial sites to clean the data, with an anticipated completion of data analysis by the third quarter of this year. Concurrently, they are investigating the cause of the liver failure that led to the halt.

Zelnecirnon is a small molecule acting as a C-C motif chemokine receptor 4 (CCR4) agonist. CCR4 is expressed by various immune cells, including T helper 2 cells, regulatory T cells, mast cells, and skin-homing lymphocytes. Inhibiting CCR4 can lead to a muted inflammatory response, beneficial for treating conditions like asthma and dermatitis. Although the complete functions of CCR4 are not entirely understood, recent studies suggest its significant role in the pathogenesis of diseases such as asthma, dermatitis, cancer, and diabetes.

The FDA's clinical hold can severely impact the development and future prospects of investigational drugs. However, there have been instances where the FDA has lifted such holds, either partially or fully, to allow companies to resume their clinical trials. For example, Cytodyn experienced a two-year wait before the FDA lifted the clinical hold on its HIV therapy, leronlimab.

Following the disruption of zelnecirnon's trials, RAPT Therapeutics' next promising candidate is tivumecirnon (FLX475), which is also a CCR4 agonist. Similar to zelnecirnon, tivumecirnon targets CCR4 expressed by regulatory T cells involved in tumor development and progression, and its inhibition fosters an antitumor response. The company is currently evaluating tivumecirnon in combination with Merck & Co’s Keytruda (pembrolizumab) for treating advanced head and neck squamous cell carcinoma in an open-label Phase II trial. Preliminary results from this trial, involving 32 patients, revealed an objective response rate of 15.6%.

Despite the challenges faced due to the clinical hold on zelnecirnon, RAPT Therapeutics continues its efforts in exploring the therapeutic potential of CCR4 agonists. The company aims to leverage its ongoing studies and data to navigate the regulatory landscape and ultimately bring effective treatments to patients suffering from various inflammatory and cancerous conditions.