Five months after the FDA rejected Regeneron’s bid for accelerated approval of its T-cell engager odronextamab because of the immaturity of its confirmatory trial, the European Union has signed off on the treatment for two types of blood cancers.
In winning the nod from the European Commission for relapsed or refractory follicular lymphoma (FL) and for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), Ordspono becomes Regeneron’s first approved bispecific antibody. The endorsement covers patients who have undergone two or more lines of systemic therapy.
Separately, the EC also granted a first-time approval to SIFI’s Akantior (polyhexanide), which becomes the first therapy to treat the rare corneal infection acanthamoeba keratitis. The sudden, parasitic disorder can cause blindness and primarily affects those who wear soft contact lenses. The Italian company has received orphan drug designation from the FDA for polyhexanide as a potential treatment for both acanthamoeba keratitis and fungal keratitis.
Regeneron’s approval was backed by phase 1 and phase 2 trials that provided remarkable data. In the ELM-2 study, patients with FL showed an 80% overall response rate (ORR), with 73% achieving a complete response (CR). The median duration of response (DoR) for the complete responders was 25 months.
In the same study, patients with DLBCL who were CAR-T therapy-naïve had a 52% ORR, with 31% reaching CR and having an 18-month median DoR.
Despite the results, the FDA sent Regeneron two complete response letters in March, rejecting the company’s application for accelerated approval because its confirmatory trials for odronextamab were not yet underway. The FDA and Regeneron need to agree to timelines of the trials “prior to resubmission,” the company said.
The rejection came as the FDA is wrestling with how to adjudicate accelerated approvals. With the recent failures of some FDA-sanctioned drugs, the approval mechanism has come under scrutiny. A recent study published in the Journal of the American Medical Association showed that 80% of drugs approved under the pathway couldn't demonstrate survival benefits after five years.
In April, the FDA's Oncology Center of Excellence chief Richard Pazdur, M.D., addressed the issue.
“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.”
In the case of odronextamab, there are other new treatments from its drug class on the market in the indications. Over the last 15 months, AbbVie and Genmab’s bispecific antibody Epkinly has gained FDA nods for both FL and DLBCL. Meanwhile, Roche has two T-cell engagers on the market: Columvi earned an FDA nod in DLBCL in June, and Lunsumino was approved by the FDA as a treatment for FL in December of 2022.
All the endorsements for the therapies have been for third-line use. In clinical trials, each of the companies, including Regeneron, is combining the T-cell engagers with other medicines in attempt to move them into earlier treatment lines.
“Ordspono marks the first approval from our bispecific antibody platform, which we hope will increasingly contribute to our growing portfolio of practice-changing medicines for oncology and other diseases,” George Yancopoulos, M.D., Ph.D., Regeneron’s chief scientific officer, said in a release.