Phase 1/2 Study for Potential Crigler-Najjar Syndrome Treatment Underway

Audentes Therapeutics has initiated the first patient dosing of VALENS, a Phase 1/2 clinical trial of a potential treatment for Crigler-Najjar syndrome called AT342.

Suyash Prasad, M.D., Senior Vice president and Chief Medical Officer said in a press release, "We greatly appreciate the opportunity to work with the Crigler-Najjar community and view the initiation of VALENS as an important milestone in our development of AT342 for this severe disease."

Crigler-Najjar syndrome is an inherited disorder in which the body is unable to break down bilirubin, a substance produced by the liver. Bilirubin eventually builds up in the bloodstream, leading to jaundice, damage to the brain, muscles, and nerves.

Current therapy consists of regular phototherapy throughout life, blood transfusions, and calcium compounds. Some patients will undergo a liver transplant operation, as well.

"There are no approved products to treat Crigler-Najjar,” Dr. Prasad continued. “The current standard of care requires most patients to spend more than 10 to 12 hours per day under phototherapy lights, and natural history data from our LUSTRO run-in study demonstrate that even with this burdensome treatment, bilirubin may only be reduced to levels just below those considered to be neurotoxic."

LUSTRO is a prospective natural history run-in study in Crigler-Najjar patients. The program will characterize the disease course and the natural history of the condition, assess the burden of disease on patients and caregivers, identify potential participants in VALENS, and serve as a longitudinal baseline and within-patient control for VALENS.

VALENS is a multicenter, multinational, open-label, randomized dose study of AT342 that evaluates the safety and efficacy of the drug. Currently, 12 Crigler-Najjar patients 1 year of age and older are included in the study.

AT342 is an AAV8 vector containing a copy of the UGT1A1 gene that will replace the mutated version of the gene in the patient. The body will then be able to metabolize bilirubin without any significant adverse events or safety findings.

The FDA has also granted AT342 Rare Pediatric Disease and Fast Track designations.

"These designations provide significant benefits, including opportunities to work with the FDA to expedite the development of AT342, and the potential to obtain a valuable Rare Pediatric Disease Priority Review Voucher upon approval,” stated Matthew R. Patterson, President and Chief Executive Officer. “We are eager to leverage these benefits and to work closely with the FDA and Crigler-Najjar patient community as we advance the development of AT342."

Preliminary data from the VALENS clinical trial will be available during the second quarter of 2018.