RAPT Therapeutics has seen its shares fall sharply after the FDA placed a clinical hold on oral CCR4 antagonist zelnecirnon, currently in a phase 2b trial for atopic dermatitis and a phase 2a trial for asthma.
The stock plunged almost 74% after the announcement of a “serious adverse event” – a case of liver failure – in the trial involving patients with atopic dermatitis, also known as eczema. RAPT said the FDA had “verbally notified” it of the decision and has yet to receive a formal letter from the regulator.
The South San Francisco-based company noted that the cause of the adverse event remains unknown “but…has been characterised as potentially related to zelnecirnon.” The FDA has asked for a full clinical hold, meaning dosing with the drug has to stop and no additional patients can be recruited into studies.
So far around 350 patients have been treated with the CCR4 inhibitor across the atopic dermatitis and asthma studies and earlier phase 1 safety study, with no signs of liver toxicity in any other participant.
The patient who suffered liver failure has a complex medical history, according to RAPT. That includes allergy to the widely-used atopic dermatitis therapy Dupixent (dupilumab) from Sanofi and Regeneron, an autoimmune disease (Hashimoto) that damages the thyroid, use of a herbal supplement associated with liver failure, and a reported COVID-19 infection at the time of the event.
“This is an unfortunate and unexpected event, and we are working diligently to get more information on this case,” said Brian Wong, RAPT’s predicant and chief executive. That includes pathology results and liver biopsy data from the patient, he said on a conference call.
“Patient safety is our top priority and we will work with the FDA to resolve this as quickly as possible.”
Analysts said the setback could result in a long delay for the zelnecirnon clinical programme, which had been due to generate results in atopic dermatitis in mid-2024, and several downgraded the company in the wake of the announcement.
There have been great expectations for zelnecirnon as an oral, once-daily alternative to injectable therapies that target Th2 inflammation, including Dupixent which has grown into a $10 billion-plus product from its use in atopic dermatitis and other TH2-mediated diseases like severe asthma and chronic rhinosinusitis with nasal polyps.
RAPT is hoping to position it ahead of injectables and JAK inhibitors – which have also been flagged for safety issues – for atopic dermatitis and other Th2 disorders, saying it represents a “pipeline in a product.”
The company’s pipeline also includes an oral CCR4 antagonist for cancer, tivumecirnon, which is in phase 2 for non-small cell lung cancer (NSCLC) and is not affected by the hold.
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