AbbVie's Epkinly follows Roche's Lunsumio in follicular lymphoma bispecific rivalry

AbbVie has announced that its bispecific antibody, Epkinly, has received accelerated approval from the FDA to treat follicular lymphoma in patients who have undergone at least two prior lines of therapy. This new approval allows Epkinly to compete directly with Roche’s Lunsumio, which received a similar approval for third-line follicular lymphoma treatment at the end of 2022. Both Epkinly and Lunsumio are CD20xCD3 bispecific T-cell engagers.

Epkinly is now distinguished as the first bispecific antibody approved to treat both follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). It initially received FDA approval in May 2023 for third-line treatment of DLBCL. In the DLBCL arena, Roche markets another CD20xCD3 drug, Columvi, and is exploring Lunsumio in combination therapies for earlier stages of treatment.

Despite the new approval, analyst Matt Phipps, Ph.D., from William Blair, predicts limited near-term sales growth for Epkinly. He attributes this to the restricted market size for later-line lymphoma treatments and Lunsumio’s first-mover advantage in follicular lymphoma, along with its suitability for outpatient settings.

Epkinly’s approval is backed by data from the phase 1/2 EPCORE NHL-1 trial, which demonstrated an overall response rate (ORR) of 82%, including 60% complete responses among 127 patients who had a median of three prior lines of therapy. After a median follow-up of 14.8 months, the median duration of response had not been reached. These findings are comparable to Lunsumio’s results in its GO29781 trial, which showed an 80% ORR with 60% complete responses and an estimated median duration of response of 22.8 months after a median follow-up of 14.9 months.

A significant advantage of Epkinly is its subcutaneous administration, unlike Lunsumio, which requires intravenous infusion. Roche is developing subcutaneous forms of its bispecific antibodies as well. Columvi and Lunsumio are administered for a fixed duration, meaning patients stop treatment after several cycles, whereas Epkinly is given indefinitely until disease progression or unacceptable toxicity.

Both Epkinly and Lunsumio are off-the-shelf therapies, making them more accessible than CD19 CAR-T treatments. The subcutaneous dosing of Epkinly offers convenience and can be administered without the need for mandatory hospitalization, according to AbbVie’s Mariana Cota Stirner, M.D., Ph.D. The 3-step-up dosing regimen during the first treatment cycle has shown a lower incidence and severity of cytokine release syndrome and neurotoxicity, while maintaining consistent efficacy compared to the original administration method used for DLBCL. Phipps noted that there is no requirement for hospitalization with the first cycle of Epkinly in follicular lymphoma, similar to Lunsumio’s label.

The follicular lymphoma approval comes shortly after the FDA halted Regeneron’s rival T-cell engager, odronextamab, for both follicular lymphoma and DLBCL. The FDA cited issues with patient enrollment in Regeneron’s confirmatory trials as reasons for the decision, aiming to ensure fair competition among pharmaceutical companies.

As attention shifts to earlier treatment settings, Genmab is conducting the phase 3 EPCORE FL-1 trial, which combines Epkinly with Roche's Rituxan and Bristol Myers Squibb's Revlimid for second-line follicular lymphoma. Concurrently, Roche is running the phase 3 CELESTIMO trial, investigating Lunsumio and Revlimid in a similar context.