HQ Team
October 1, 2024: Kezar Life Sciences Inc., a US-based biotechnology company, has stopped a trial in patients with a type of kidney disease after four people died.
The cessation of the trial followed a mid-stage evaluation of the efficacy and safety of two dose levels of zetomipzomib in patients with active lupus nephritis.
Zetomipzomib, a selective immunoproteasome inhibitor, is currently being evaluated in a Phase 2b clinical trial for lupus nephritis and a Phase 2a clinical trial for autoimmune hepatitis.
Lupus nephritis is a type of kidney disease caused by systemic lupus erythematosus link or lupus. Lupus is an autoimmune disease link—a disorder in which the body’s immune system attacks the body’s cells and organs.
Committee’s recommendations
Eighty-four patients in the lupus nephritis trial were randomly treated with 30 mg of zetomipzomib, 60 mg of zetomipzomib or a dummy drug subcutaneously once weekly for 52 weeks, in addition to standard background therapy.
An Independent Data Monitoring Committee reviewed the patient safety data.
“Kezar has suspended enrollment and dosing,” at the committee’s recommendation “including an assessment of four Grade 5 (fatal) serious adverse events that have occurred during the trial in patients enrolled in the Philippines and Argentina,” according to a statement.
A review of the data by the committee “revealed that three of the fatalities showed a common pattern of symptoms and proximity to dosing,” and an additional non-fatal serious adverse event showed “similar proximity to dosing.”
Kezar has not observed any death or serious opportunistic infections in prior clinical studies of zetomipzomib, according to the statement.
Notified regulators
The California-headquartered company’s decision to pause enrollment and dosing gives it time to evaluate the totality of data regarding serious adverse events and determine the next steps and potential risk mitigation strategies.
The company has notified all study investigators and is notifying regulatory authorities, including the US Food and Drug Administration and the European Medicines Agency, of its decision.
“Our top priority is the safety of every patient who participates in our clinical trials,” said Chris Kirk, PhD, Kezar’s Chief Executive Officer. “Lupus nephritis represents a life-threatening medical condition in need of new therapies.”
“We will continue to work with the site investigators to learn more about each of these cases and hope to have an informed discussion with the independent committee and regulatory authorities as we look to continue the zetomipzomib development program in lupus nephritis and autoimmune hepatitis.
“We will provide additional information regarding this investigation and the zetomipzomib development program at the appropriate time,” he said.
Women more vulnerable
Kezar’s ongoing Phase 2a clinical trial of zetomipzomib in patients with autoimmune hepatitis has completed enrollment and remains active. “No Grade 4 or 5 serious adverse events have been observed in the clinical trial,” for hepatitis, according to the statement.
Lupus is much more common in women than in men and most often strikes during the childbearing years. Nine out of 10 people who have lupus are women, according to the National Institutes of Health.
Lupus is also more common in people of African or Asian background. African Americans and Asian Americans are about 2 to 3 times more likely to develop lupus than Caucasians.
In the United States, 1 out of every 250 African American women will develop lupus.
Kidney damage is one of the more common health problems caused by lupus. In adults who have lupus, as many as 5 out of 10 will have kidney disease. In children who have lupus, 8 of 10 will have kidney disease.
