The FDA clinical hold follows a a report of liver failure that may be associated with zelnecirnon, an experimental Rapt Therapeutics drug. The biotech notes that no other patient has experienced liver problems and this safety signal has not been seen in any other tests of the molecule.

By FRANK VINLUAN
Rapt Therapeutics aim to bring patients oral alternatives to injectable or infused immunology medications has hit a setback. A Rapt drug candidate in mid-stage clinical development in atopic dermatitis and asthma has been placed under an FDA clinical hold after a serious adverse event reported in a study participant, the company announced Tuesday.

The patient, a participant in the atopic dermatitis study, experienced liver failure. According to Rapt, the cause of the liver failure is unknown but has been characterized as potentially related to the company’s experimental drug, zelnecirnon. South San Francisco-based Rapt said the FDA verbally notified the company of the clinical hold on the atopic dermatitis and asthma clinical trials. A formal letter is forthcoming. Meanwhile, dosing of the once-daily tablet has been halted in both studies, which have also stopped enrolling new trial participants.

Many of the new drugs for immunological conditions are large molecule biologics, which can’t be made into oral drugs the way small molecules can. Rapt discovers and develops small molecules capable of addressing immune responses in immunology and oncology. Zelnecirnon, formerly known as RPT193, is Rapt’s lead inflammation drug candidate. This molecule is designed to target CCR4, a cell surface receptor that plays a role in the migration and homing of immune cells to tissues in the body. Zelnecirnon is intended to selectively inhibit the migration of type 2 T helper cells into inflamed tissues.

“We chose to pursue atopic dermatitis as the first indication for RPT193 because we believe the characteristics of the disease present an opportunity to rapidly demonstrate RPT193’s anti-inflammatory effect with the potential for good translatability to later-stage clinical trials,” the company said in its 2022 annual report.

In Phase 1b clinical trial testing of zelnecirnon in 31 patients with moderate-to-severe AD, results reported in 2021 showed that those who received the experimental drug showed greater improvement from baseline compared to the placebo group measured by several standard assessments of the disease’s severity. The company proceeded to separate Phase 2 tests in moderate-to-severe atopic dermatitis and moderate-to-severe asthma.

Across all three zelnecirnon studies so far, Rapt said about 350 patients have been enrolled. No participants have shown evidence of liver toxicity, nor has that safety signal turned up in animal or laboratory tests, the company added. According to Rapt, the patient had a complex medical history. In addition to an allergy to Dupixent, the blockbuster Sanofi and Regeneron Pharmaceuticals immunology drug, this patient had an autoimmune disease that required thyroid replacement therapy. Furthermore, the patient used an herbal supplement known to be associated with liver failure and also reported a Covid-19 infection while experiencing the liver failure.

“This is an unfortunate and unexpected event, and we are working diligently to get more information on this case,” Rapt President and CEO Brian Wong said in a prepared statement. “Patient safety is our top priority and we will work with the FDA to resolve this as quickly as possible.”

Rapt said the clinical hold does not affect the company’s ongoing Phase 1/2 test of tivumecirnon, formerly known as FLX475, in cancer.

Shares of Rapt closed Tuesday at $6.88 each, down more than 73% from Friday’s closing stock price.
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