With Regeneron’s treatment delayed, AbbVie is expanding its T-cell engager competition against Roche in blood cancer with a new FDA approval.
The FDA has signed off on AbbVie and Genmab’s Epkinly to treat follicular lymphoma after at least two prior lines of therapy.
Wednesday’s accelerated approval allows Epkinly to go toe to toe with Roche’s Lunsumio, which got its own third-line follicular lymphoma nod at the end of 2022. Both drugs are CD20xCD3 bispecific T-cell engagers.
AbbVie was eager to highlight that Epkinly is now the first bispecific antibody approved to treat both follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). The drug received its initial FDA go-ahead in May 2023 for the third-line treatment of DLBCL. In DLBCL, Roche is selling another CD20xCD3 med, Columvi, and is testing Lunsumio as part of a combination in an earlier treatment setting.
Nevertheless, William Blair analyst Matt Phipps, Ph.D., sees only a limited near-term sales expansion for Epkinly. In making that projection, he cited the “limited market size for later-line lymphoma indications, as well as Lunsumio’s first-mover advantage in follicular lymphoma and similar applicability in outpatient settings,” according to a Thursday note.
Epkinly’s latest nod features tumor shrinkage data from the phase 1/2 EPCORE NHL-1 trial. The trial showed an overall response rate (ORR) of 82%, including 60% complete responses, for Epkinly among 127 patients who had previously tried a median of three lines of therapy. The median duration of response was not reached after a median follow-up of 14.8 months among responders.
Epkinly’s efficacy data look very similar to Lunsumio’s result from its own GO29781 trial, which recorded an 80% ORR, with 60% complete responses. After a median follow-up of 14.9 months among responders, the estimated median duration of response was 22.8 months.
Compared with Lunsumio, which is administered as an intravenous infusion, Epkinly boasts the advantage of being a subcutaneous injection. Roche, for its part, is eagerly advancing subcutaneous versions of its bispecifics.
Roche developed Columvi and Lunsumio in fixed durations, meaning patients stop treatment after a few cycles. Epkinly, by comparison, is given indefinitely until disease progression or unacceptable toxicity.
As readily available off-the-shelf therapies, Epkinly and Lunsumio are simpler to access than CD19 CAR-T therapies.
“Subcutaneous dosing offers convenience, and Epkinly can be given to patients without mandatory hospitalization using a 3-step-up dosing regimen,” AbbVie’s therapeutic area head for hematology, Mariana Cota Stirner, M.D., Ph.D., said in a statement Wednesday.
The 3-step-up dosing protocol for the first cycle of treatment has shown lower incidence and severity of cytokine release syndrome and neurotoxicity but consistent efficacy compared with Epkinly’s original administration strategy used in the DLBCL indication, William Blair’s Phipps pointed out.
In his note, Phipps said his team is “notably encouraged to see no requirement for hospitalization upon first cycle administration” of Epkinly in the follicular lymphoma indication, similar to the label of Roche’s Lunsumio.
AbbVie and Genmab added the follicular lymphoma label three months after the FDA blocked Regeneron’s rival T-cell engager odronextamab in both follicular lymphoma and DLBCL.
In its complete response letters, the FDA cited concerns around enrollment for Regeneron’s confirmatory trial programs. In explaining the decision at an American Association for Cancer Research event in April, the FDA’s oncology chief Richard Pazdur, M.D., said the move was meant to level the playing field among drug developers.
“If we really believe that there are no other therapeutic alternatives, then there will be obviously some degree of flexibility,” Pazdur said. “When we do see, however, that there may be accelerated approval with the same class of drugs with the same diseases and with sponsors previously having most of the confirmatory study accrual already completed at the time of accelerated approval, we have to have a level playing field for all of the pharmaceutical companies.”
With the late-line uses now endorsed by the FDA, attention around the rival bispecifics has turned to earlier treatment settings.
Genmab’s phase 3 EPCORE FL-1 trial is combining Epkinly with Roche's Rituxan and Bristol Myers Squibb's Revlimid in second-line follicular lymphoma. For Roche, the phase 3 CELESTIMO trial is investigating Lunsumio and Revlimid also in the second-line setting.