Novartis dumps 2nd bispecific from $2.6B Xencor pact, dealing further blow to hopes for blood cancer target

Novartis has hacked off another piece of its $2.6 billion deal with Xencor, terminating its rights to a CD123xCD3 blood cancer bispecific that had a troubled time in early clinical development.

Xencor granted Novartis ex-U.S. rights to CD123xCD3 candidate vibecotamab and a second bispecific antibody back in 2016. Novartis dumped the other drug candidate, XmAb13676, in 2019, but it stuck by vibecotamab as Xencor battled through a partial clinical hold triggered by two patient deaths that were considered at least possibly related to the bispecific and went on to post phase 1 data.

Now, Novartis is cutting its ties to vibecotamab. The Swiss Big Pharma communicated its decision to Xencor in August and will complete the termination of its rights in February, when a phase 1 study of vibecotamab is scheduled to wrap up. Novartis will cover its share of the costs until August 2022.

The action marks the end of active development of vibecotamab, with Xencor opting against taking the candidate forward itself. The termination of work on vibecotamab marks another blow to hopes that CD123 offers a way to improve outcomes in patients with acute myeloid leukemia (AML).

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CD123 is upregulated in AML, leading drug developers to deploy a range of modalities against the target. Companies including CSL and Johnson & Johnson trialed anti-CD123 monoclonal antibodies only to stop work in response to lackluster efficacy. Seagen dropped a CD123 antibody-drug conjugate in response to safety concerns, but ImmunoGen is still applying the modality to the target.

Multiple groups including Novartis, Sanofi and J&J identified bispecifics as a better way to go after CD123, but the programs have been beset by problems. J&J’s Genmab-partnered candidate suffered clinical holds in phase 1. The study wrapped up earlier this year. Genmab still lists the drug in its pipeline, but further clinical development is yet to start. Sanofi terminated a trial of its drug this year.

Aptevo Therapeutics and MacroGenics have active clinical trials of CD123 bispecifics, but the field has thinned considerably, denting hopes that the modality is the key to unlocking the therapeutic power of the target.   

For Xencor, Novartis’ decision to ditch vibecotamab ends collaboration on the two headline assets in the 2016 agreement. However, the agreement could yet spawn a success, with Novartis selecting a candidate developed under another part of the deal in June. Novartis is fully responsible for taking the candidate forward.