Earlier this month, Kezar Life Sciences announced that the mid-stage test of zetomipzomib in lupus nephritis had been placed on an FDA clinical hold. Now, that program is being terminated.
Kezar Life Sciences is discontinuing a lupus program after four patient deaths occurred during a Phase IIb trial and will focus on developing the same drug in autoimmune hepatitis.
Earlier this month, Kezar announced that the mid-stage study of zetomipzomib in lupus nephritis had been placed on an FDA clinical hold. The regulatory action came after the company reported four patient deaths in the Phase IIb PALIZADE trial. Other serious adverse events were reported as well that “showed a similar proximity to dosing.” Kezar voluntarily suspended enrollment and began looking at mitigation strategies for the drug.
Now, an independent data monitoring committee that had been examining the PALIZADE trial and the Phase IIa PORTOLA trial of zetomipzomib in hepatitis has recommended that the lupus program be suspended. Kezar will proceed with the hepatitis study and expects a readout in the first half of 2025, according to a Thursday press release.
Kezar noted that one of the deaths that occurred in the PALIZADE study was in a patient who had received a placebo. The trial was conducted in Argentina and the Philippines. The trial will be unblinded and a full investigation will be conducted into the safety events, the company said. At the time the study was terminated, 84 patients were enrolled. Kezar promised to release available data at a later time.
CEO Chris Kirk said Kezar’s decision was a difficult one, as the company had seen a favorable safety profile and clinical activity in an earlier trial called MISSION. The PALIZADE trial also enrolled very quickly.
“However, a focused development effort in AIH [autoimmune hepatitis] extends our cash runway and provides flexibility as we work to bring zetomipzomib forward as a treatment for patients living with this life-threatening disease,” Kirk said.
The data committee recommended that the PORTOLA trial proceed without modification after examining all safety data from the patients enrolled in the trial. No serious adverse events rated grade 4 or higher, which would indicate a death, have occurred in the PORTOLA trial which is being conducted in the U.S.
In other news, Kezar has rejected an unsolicited bid from Concentra Biosciences to acquire the biotech. The offer had been to buy all outstanding shares for $1.10 apiece, plus a contingent value right. Kezar has decided that the value significantly undervalues the company and zetomipzomib.
Concentra, meanwhile, has moved to acquire 9.9% of Kezar’s common stock. Kezar has adopted a stockholder rights plan, also known as a “poison pill” defense, to protect against any party buying a controlling stake through the open market without paying stockholders their due.
The rights plan does not block a more traditional buyout, even from Concentra, if the board deems it in the best interests of shareholders, Kezar noted.
Kezar’s shares were trading at 80 cents on the Nasdaq Capital Market Thursday morning, down more than 9% from the prior close.
Concentra is owned by Tang Capital, a life sciences-focused investment firm. The company has made many attempts over the years to buy out struggling biotechs, most recently succeeding in acquiring Theseus Pharmaceuticals. Similar buyouts offered to LianBio, Rain Oncology and Atea Pharmaceuticals were unsuccessful.
