AbbVie, Genmab's Epkinly shows promise in follicular lymphoma. Will FDA get on board?

Merely a month into an FDA approval, AbbVie and Genmab’s bispecific drug Epkinly has chalked up a positive readout that might enable an expansion in blood cancer, although the exact regulatory path remains unclear.

Epkinly significantly beat back tumors in 82% of patients with relapsed or refractory follicular lymphoma in a phase 1/2 trial, the companies said Tuesday. The patients had received a minimum two—and a median three—prior lines of systemic therapy.

The median duration of response hasn’t been reached in Epkinly’s study, and investigators are still following patients. The companies also didn’t disclose the complete response rate. Full results from the study will be shared at a future medical meeting.

Epkinly snagged an FDA approval for previously treated diffuse large B-cell lymphoma (DLCLC) in May, and AbbVie and Genmab said they will talk to regulators about next steps in FL, an indolent form of lymphoma. If approved in the indication, Epkinly would go up against Roche’s first-in-class Lunsumio. The two parties are already battling it out in DLBCL thanks to an FDA go-ahead for Roche’s Columvi a few days ago. All three drugs are CD20xCD3 T-cell engagers.

Based on Lunsumio’s precedent, it’s possible for Epkinly to win an FDA nod based on a single-arm trial.

At first glance, Epkinly’s data look mixed compared with Lunsumio’s by cross-trial comparison. Lunsumio triggered a response in 80% of FL patients who had previously tried a median three prior lines of therapy in a phase 2 trial. Half of the Lunsumio patients were refractory to both anti-CD20 antibody and alkylating agents. Epkinly’s 82% overall response rate had 70% of patients who were double refractory.

On the safety side, Epkinly recorded 66.4% cytokine release syndrome, which is a common  side effect among T-cell therapies. These include 1.6% cases that are grade 3 or higher. Lunsumio’s overall CRS rate is much lower at 39%, including 2.5% of grade 3 or above. Between Lunsumio and Columvi, Roche has directed Lunsumio at FL—instead of the more aggressive DLBCL—because it’s more tolerable.

But William Blair analyst Matt Phipps, Ph.D., suggested that Epkinly will only get a smaller market in previously treated FL, reaching $289 million sales in 2027 in the U.S. alone. Lunsumio’s first-to-market status and the lack of hospitalization requirements during dose escalation give the Roche drug an edge over Epkinly, Phipps said in a Wednesday note to clients.

The 128-patient data that AbbVie and Genmab disclosed didn’t include anyone from a phase 2a optimization part of the trial, Phipps pointed out in his note, citing Genmab. Investigators are testing alternative dosing regimens to mitigate the risk of CRS, and early data from the first few patients indicated a “clinically meaningful” improvement in CRS rate, Genmab said in a release Wednesday.

AbbVie and Genmab added the optimization part in accordance with the FDA’s Project Optimus, which is asking drug developers to more carefully examine the optimal dose of drugs, according to Genmab. The request “suggests the FDA is focusing on reducing these [CRS] rates even further going forward,” Phipps said. How much data the FDA wants to see from an optimized dosing schedule of Epkinly could determine the timing of the drug’s regulatory filing, he added.

Drugs for FL contributed to the idea of Project Optimus. The FDA has previously pushed for the market withdrawals of several PI3K inhibitors by Gilead Sciences, TG Therapeutics and Secura Bio in FL because of safety concerns. The agency cited the lack of optimal dose exploration as a reason for the drugs’ failure.