Turbulent times for Xencor as FDA slaps hold on AML bispecific

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Patients that are being treated and “benefiting from treatment” may continue on the phase 1 study, but no new patients will be able to enroll until the FDA lifts the hold. (FDA)

Xencor didn’t have the best start to 2019—in January, its partner Novartis returned the rights to a bispecific antibody it had licensed as part of a 2016 deal worth up to $2.41 billion. Now, a second asset from that deal, in development for acute myeloid leukemia (AML), has hit a snag in the form of a partial clinical hold from the FDA.

The hold affects a phase 1 trial of XmAb14045, an antibody targeting CD123 and CD3, in patients with relapsed or refractory AML and other CD123-expressing hematologic malignancies. The FDA placed the hold after Xencor submitted safety reports about two patient deaths that were “considered at least possibly” treatment-related. One patient had cytokine release syndrome (CRS) after the first dose of XmAb14045, while the other developed acute pulmonary edema after several doses.

The study is on partial hold while the agency reviews details around the deaths, as well as safety and efficacy data across the study, amendments to the study protocol and related documents, Xencor said in a statement. Patients that are being treated and “benefiting from treatment” may continue on the study, but no new patients will be able to enroll until the FDA lifts the hold.

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"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,” said Xencor CEO Bassil Dahiyat, Ph.D., in the statement.

RELATED: In R&D rethink, Novartis ditches part of $2.6B Xencor bispecific pact

Under Xencor’s original deal with Novartis, the partners agreed to develop XmAb14045 for AML and XmAb13676 for B-cell malignancies. The Big Pharma handed over $150 million upfront and promised up to $2.41 billion in clinical, regulatory and sales milestones. Novartis also secured the worldwide rights to four additional targets to be engineered by Xencor and a worldwide, nonexclusive license to use Xencor’s XmAb Fc technology in up to 10 molecules.

Two and a half years later, Novartis handed back the rights to XmAb13676, an antibody targeting CD20 and CD3, due to a pipeline reprioritization. But it is still working on XmAb14045 with Xencor and will “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.”

RELATED: Xencor’s lead lupus antibody misses phase 2 endpoint

It hasn’t all been doom and gloom for Xencor though. A month after Novartis backed away from XmAb13676, Xencor struck a deal that saw Genentech pay up $120 million upfront to gain the rights to its preclinical IL-15 cytokine therapeutics.

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