AbbVie and Genmab’s bispecific antibody blew analyst expectations out of the water with a 51% improvement in progression-free survival when used alongside a standard frontline regimen in diffuse large B cell lymphoma—potentially setting up a battle with Roche’s Polivy.
When used in the frontline setting on top of a common anti-cancer regimen, AbbVie and Genmab’s Epkinly cut the risk of disease progression or death by more than half in patients with newly diagnosed diffuse large B cell lymphoma—besting the results of Roche’s Polivy and potentially positioning the drug as “the new standard of care” in this indication, according to William Blair.
The progression-free survival (PFS) benefit seen with Epkinly, already approved for later lines of treatment in diffuse large B cell lymphoma (DLBCL), is the strongest treatment effect disclosed among major registrational trials in frontline treatment of the cancer, the analysts wrote wrote in a Monday afternoon note to investors. The readout “knocks it out of the park,” they said.
The EPCORE DLBCL-2 trial, which enrolled 900 patients, is the first Phase 3 study of a bispecific antibody combination therapy to show statistically significant improvement, AbbVie and Genmab said in a press release on Monday.
Compared with treatment with only R-CHOP—a five-drug regimen based on Roche’s rituximab—the Epkinly-based combo led to a 51% reduction in the risk of disease progression or death, AbbVie and Genmab reported Monday. Not only did the result hit the study’s primary endpoint, it greatly exceeded analyst expectations of a 30–35% benefit. This PFS benefit was the same for patients with high-risk and low- to intermediate-risk disease.
“We view the result as highly differentiated and squarely within our best-case scenario, ” Truist Securities analysts wrote to investors on Monday.
As for safety, the companies noted that using Epkinly with R-CHOP was generally well-tolerated, with side effects consistent with what is known for the individual drugs.
Genmab shares popped nearly 11% at close of trading to $38.48 following the data reveal.
The company originally partnered with AbbVie in 2020 to collaborate on the development of Epkinly, a CD20xCD3 bispecific T cell engager, that was first approved in May 2023 for patients with for DLBCL who have undergone at least two prior lines of systemic treatment. If greenlit in the first-line setting, Epkinly will compete with Roche’s Polivy and potentially Incyte’s Monjuvi.
AbbVie and Genmab plan to bring the new data to global regulatory authorities to determine the next steps for the investigational combo. The partners also plan to present a more complete analysis of EPCORE DLBCL-2 at an upcoming medical meeting.
Epkinly’s Phase 3 results compare favorably to benchmarks set by existing treatment regimens based on Monjuvi and Polivy, William Blair said.
Polivy was approved by the FDA for first-line DLBCL in April 2023 after the drug, combined with a modified version of R-CHOP reduced the risk of disease progression, relapse or death by 27% in a Phase 3 trial.
Monjuvi plus R-CHOP, meanwhile, hit 25% progression-free survival in a Phase 3 trial in January, meeting the study’s primary endpoint. Incyte indicated plans at the time to file for FDA approval in the indication in the first half of this year.
AbbVie and Genmab’s readout represents an “overwhelmingly positive improvement” in favor of the Epkinly combo, William Blair said, noting that the data significantly exceeded the firm’s base case scenario. The firm had originally anticipated a 35% PFS benefit. Truist, meanwhile, had expected the Epkinly regimen to cut the likelihood of disease progression or death by 30%.
Truist also emphasized the consistency of Epkinly’s ability to reduce disease progression across risk groups, a robust treatment effect the analysts “should support regulatory discussion across the broader population.
“While full data remain important for absolute benefit, durability, OS, and safety, the topline result supports a potentially practice-changing profile and a credible path toward a broad 1L label, in our view,” Truist continued.
The study is expected to wrap up in June 2027, according to Clinicaltrials.gov.
Notably, Epkinly in January failed to improve survival in a separate Phase 3 study in patients with relapsed, refractory DLBCL who are ineligible for or for whom prior treatments have not worked, missing the trial’s primary endpoint.
