FDA Places Partial Clinical Hold on Xencor Clinical Trial Following Two Patient Deaths

The U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on Xencor’s Phase I acute myeloid leukemia study due to the death of two patients in the trial.

In an announcement this morning, Xencor said the regulatory agency has halted new enrollment of patients in the Phase I trial assessing XmAb14045, a CD123 x CD3 bispecific antibody molecule being evaluated in patients with relapsed or refractory acute myeloid leukemia and other CD123-expressing hematologic malignancies. Xencor said the FDA placed the partial clinical hold following recent safety reports submitted by the company. The company sent the report following the death of two patients, which could be related to XmAb14045, the company said.

According to its announcement, one of the patients in the study experienced cytokine release syndrome after receiving the first dose of XmAb14045. Xencor said the treatment of the cytokine release syndrome was complicated due to the patient’s decision to withdraw from care. The other patient developed acute pulmonary edema following several doses of XmAb14045, Xencor said this morning.

The FDA has placed the trial on partial clinical hold pending review of additional details regarding these events, safety and efficacy information across the study, and satisfactory review of amendments to the study protocol and related documents. Xencor will be working closely with the FDA to review these events and resolve the partial clinical hold.

Bassil Dahiyat, president and chief executive officer of Moravia, Calif.-based Xencor, said patient safety is the highest concern of the company.

“We are working with the investigators and the FDA and will provide an update when more information about resuming enrollment can be shared. Our ongoing Phase 1 studies evaluating our other CD3 bispecific antibodies, XmAb13676 and XmAb18087, are not affected,” Dahiyat said in a statement.

Earlier this year, Xencor regained the rights to develop and commercialize XmAb13676, a CD20 x CD3 bispecific antibody, from Novartis effective June 20, 2019. The company regained control of the asset after the Swiss pharma giant initiated a strategic pipeline reprioritization. Xencor granted Novartis co-development and ex-U.S. commercial rights in June 2016 through a collaboration and license agreement to develop and commercialize novel bispecific antibodies.

Under terms of the 2016 collaboration agreement, Xencor and Novartis continue to share costs for the worldwide development of XmAb14045 with Xencor maintaining U.S. commercialization rights and Novartis having commercialization rights in the rest of the world, and worldwide development costs for XmAb13676 will be shared until June 2020.