Chasing Roche, AbbVie posts data on CD20 blood cancer bispecific ahead of race to regulators

AbbVie has fired back in the fierce fight for the CD20 bispecific market. Phase 1/2 data show AbbVie and Genmab’s epcoritamab triggers responses in heavily pretreated blood cancer patients, although the first report of grade 3 cytokine release syndrome (CRS) could dent hopes of delivering best-in-class safety.

The potential for CD20xCD3 bispecifics to turn T cells against malignant B cells, driving CAR-T-like efficacy in non-Hodgkin lymphoma (NHL) without the complexity associated with cell therapies, has attracted a who’s who of top drug developers. Roche, which has two candidates in the race, is leading the pack with its Biogen-partnered mosunetuzumab. Johnson & Johnson, Regeneron and more are giving chase. 

AbbVie is breathing down Roche’s neck. Late Wednesday, AbbVie and Genmab shared top-line data on their CD20xCD3 bispecific epcoritamab in 157 patients with relapsed/refractory large B-cell lymphoma (LBCL), a fast-growing type of NHL. Participants had received at least two prior lines of systemic therapy. The mean lines of prior therapy was 3.5, with at least one patient having 11 lines. Almost 40% of patients had previously received CAR-T cell therapy.

In that heavily pretreated population, epcoritamab had an overall response rate of 63.1% and a median duration of response of 12 months. The response rate is down in the 88% seen in the eight diffuse LBCL who took the recommended phase 2 dose in the dose-escalation part of the trial, potentially because of differences in the patient populations. Participants in the earlier part of the trial had previously received between two and four lines of therapy. Around 10% had received a CAR-T.

Analysts at Jefferies called the efficacy “robust,” adding that it appeared to be in line with expectations. However, the analysts spotted a fly in the ointment, cautioning that the “first occurrence of Grade 3 CRS with monotherapy dampens epco's potentially best-in-class safety profile.”

Half of the participants experienced CRS. Most of the cases were mild, but 2.5% of participants suffered grade 3 CRS. The analysts are waiting on the full data before passing judgment, noting that the patients who previously received CAR-T may have been at high risk for CRS, but the finding could be a blow. Other CD20xCD3 bispecifics have also caused grade 3 CRS. The Jefferies analysts compared the data to results from a phase 1 trial of Roche’s glofitamab, in which 4% of patients had grade 3 CRS and 3% had grade 4.

AbbVie and Genmab are now preparing to talk to global regulatory agencies about the data and the next steps for epcoritamab. The Jefferies analysts warned “recent FDA guidelines may delay further phase 3 initiations pending additional dose evaluation studies, potentially extending competitor Roche's lead, with CD20xCD3 mosentuzumab filed, glofitamab filing imminent,” but still tip epcoritamab to generate peak sales of $2.75 billion.