Deaths spur partial hold for Xencor’s CD3 bispecific for leukemia, partnered with Novartis in $2.5B deal

Researchers at Xencor have slammed the brakes on recruiting more patients for an early-stage study of XmAb14045, a CD123 x CD3 bispecific antibody in the race for acute myeloid leukemia. 

The company says that the FDA dropped the hold on them after they tracked 2 deaths in the study that could be linked to the bispecific — one from cytokine release syndrome and another from acute pulmonary edema following several doses. The CRS case was complicated by the patient’s decision to withdraw from the study, according to the company.

Bassil Dahiyat

CD3 bispecifics are all the rage these days, inspiring a $2.5 billion deal with Novartis back in 2016 that was fronted with a $150 million cash payment. That gave the pharma giant dibs on XmAb14045 and XmAb13676. Ironically, Novartis opted to hand back rights to XmAb13676 just weeks ago while keeping its ties with Xencor $XNCR on ‘14045.

This isn’t the first time a CD123 x CD3 has run into a clinical hold. J&J’s AML study for JNJ-63709178 was put on a full hold by the FDA back in 2016 — though the company wouldn’t say at the time what adverse events were involved. MacroGenics, meanwhile, had its own partial hold to deal with for its B7-H3 × CD3 bispecific late last year after researchers spotted signs of livery toxicity in patients.

Now you can expect plenty of more questions about what kind of safety issues these bispecifics pose as developers race each other to the finish line. That could be especially troubling for Xencor, particularly after J&J dropped it drug talacotuzumab (JNJ-56022473/CSL362) for acute myeloid leukemia in 2017. That Phase III drug, originally from CSL, uses Xencor’s antibody tech.

Bassil Dahiyat, president and chief executive officer at Xencor, noted this morning: 

“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.”

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