Phase 1 Trial of Therapy for Autoimmune Diseases, Including Lupus, Initiated by Kezar
Kezar Life Sciences, a San Francisco-based company focused on the development of therapies targeting protein homeostasis, recently initiated a Phase 1 clinical trial assessing KZR-616, a potential treatment for multiple autoimmune and inflammatory diseases, including lupus.
Together with a medical team in Australia, the study will be performed in a randomized, double-blind manner. Its aim is to determine the safety and tolerability, as well as the pharmacokinetics and pharmacodynamics profile of KZR-616 in healthy subjects.
The trial is expected to enroll a total of 64-80 volunteers who will receive once-weekly injections of a single or multiple ascending dose of either KZR-616 or a placebo. So far, the company has enrolled and completed the dosing regimen in 24 subjects.
The company expects the first results to be available by the end of 2016. Kezar also anticipates it will be possible to start, in the first half of 2017, a second stage study (Phase 1b) of KZR-616 that will include up to 40 patients with autoimmune disorders.
KZR-616 is a small molecule inhibitor that selectively targets the immunoproteasome, which is responsible for the control of several cellular physiological processes in immune system cells as cellular death and cytokine production.
Specific immunoproteasome inhibition can block the production of key inflammatory cytokines that are already approved therapeutic targets.
Moreover, immunoproteasome inhibition can block the function of T-cell subsets known to promote autoimmunity; at the same time, it can restore the regulatory T-cell subset that is normally nonfunctional during inflammation.
Importantly, immunoproteasome inhibitors have shown to present low toxicity and to allow normal immune responses in experimental animal models. It was previously shown that the immunoproteasome is more expressed at inflammation sites in patients with autoimmune disorders. This indicates that the immunoproteasome can be a suitable drug target for the suppression of overactive immune cell responses in complex autoimmune inflammatory diseases.
“We are proud to be the first company to move a selective inhibitor of the immunoproteasome into the clinic,” Kezar CEO John Fowler said in a press release. “The Kezar scientific team is unparalleled in its understanding of the unique biology and therapeutic potential of the immunoproteasome, and has done a tremendous job moving our lead program rapidly into the clinic. We look forward to demonstrating the safety profile and target engagement of KZR-616 in the coming months, and launching Phase 1b and 2 trials in patients in 2017.”
Kezar’s research team has studied the impact of KZR-616 in several chronic inflammatory diseases, including systemic lupus erythematous (SLE), rheumatoid arthritis, multiple sclerosis, type 1 diabetes, and inflammatory bowel disease.
In experimental mouse models of SLE, in particular, the team showed that KZR-616 treatment could slow disease progression. This was achieved by the control of two key pathways in the development of the disease: type 1 interferon activation and autoantibody production by plasma cells. KZR-616 may therefore represent a powerful therapeutic agent for the treatment of SLE.
“Initiation of the KZR-616 clinical program represents an exciting milestone for our extensive research program to develop a first-in-class treatment that can address substantial unmet needs across many autoimmune disorders,” said Christopher Kirk, PhD, Kezar’s president and chief scientific officer.
“We believe that the immunoproteasome is a profoundly untapped area of translational medicine. Our scientific research has shown that selective inhibitors of the immunoproteasome have the potential to reset normal immune function in patients with complex and difficult-to-treat autoimmune diseases,” Kirk said.