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FDA Clears Autoimmune Hepatitis Treatment, Zetomipzomib, As Investigational New Drug

The FDA cleared zetomipzomib as an Investigational New Drug. A phase 2 clinical trial is the next step for this autoimmune hepatitis treatment.

This week, Kezar Life Sciences, Inc. announced their autoimmune hepatitis treatment had received clearance of an Investigational New Drug (IND) application by the US Food and Drug Administration (FDA).

The therapy, zetomipzomib, is a first-in-class, selective immunoproteasome inhibitor, intended for the treatment of autoimmune hepatitis (AIH). AIH is a rare chronic disease that causes the immune system to attack the liver. This leads to inflammation and tissue damage that ultimate severely burdens patients’ health and quality of life.

AIH affects approximately 140000 persons in the US, with incidence rates 4 times higher in women than men. Left untreated, AIH can lead to cirrhosis, liver failure, and hepatocellular carcinoma.

While there are AIH treatments currently available, these chronic corticosteroids can increase the burden of morbidity and mortality. With zetomipzomib, Kezar Life Sciences seeks to provide a treatment regimen to reduces the need for chronic immunosuppression via corticosteroids.

“Patients with autoimmune hepatitis need new therapies that can better treat their disease,” said Craig Lammert, MD, an assistant professor of medicine at Indiana University and executive director of the Autoimmune Hepatitis Association. “Lifelong maintenance therapy is required for most patients with AIH and an alternative regimen that reduces or removes the need for immunosuppression with corticosteroids would be welcomed by patients and the medical community.”

With this FDA clearance, Kezar Life Sciences plans to launch the phase 2 PORTOLA trial. “Zetomipzomib is a unique small molecule with the potential to be a non-immunosuppressive, anti-inflammatory treatment for multiple autoimmune diseases,” said Noreen R. Henig, MD, Kezar’s chief medical officer. “We plan to run PORTOLA, an early proof-of-concept study in parallel to our other development efforts, including a late-phase efficacy trial for patients with lupus nephritis and a potential program in patients with systemic lupus erythematosus.”

This randomized, double-blind, placebo-controlled clinical study will evaluate the safety and efficacy of zetomipzomib for AIH patients who responded insufficiently to standard care or have relapsed. The target enrollment is 24 patients, who will be randomly assigned 2:1 to receive either zetomipzomib with prednisone or placebo with prednisone for 24 weeks. By week 14, study patients will receive a protocol-directed steroid taper.

The primary efficacy endpoint will evaluate the proportion of patients who achieve a complete response, measured as normalization of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels with a successful corticosteroid taper by Week 24.

Zetomipzomib (KZR-616) is a novel, first-in-class, selective immunoproteasome inhibitor that may have potential to treat multiple autoimmune diseases. Preclinical research suggested selective immunoproteasome inhibition causes a broad anti-inflammatory response in animal models across several autoimmune diseases, while simultaneously avoiding immunosuppression. Data generated from phase 1 clinical trials found zetomipzomib has a favorable safety and tolerability profile.