Regeneron Pharmaceuticals is years into an ambitious plan to become a top cancer drug developer. Over the past two days at the year’s biggest meeting on blood disease research, the New York biotechnology company showcased two experimental drugs it views as critical to its plan’s success.
Called odronextamab and linvoseltamab, the drugs are for the blood cancers lymphoma and multiple myeloma, respectively. Presentations at the American Society of Hematology’s annual meeting Sunday and Monday involved data from early- and mid-stage studies, building on evidence that could eventually support regulatory approvals.
Regeneron is counting on it. The drugs are important to the future of the biotech, which is best known for the eye drug Eylea and the anti-inflammatory medicine Dupixent. However, in recent years it has invested more heavily in oncology. The company has one cancer drug approved, the immunotherapy Libtayo. It views odronextamab and linvoseltamab as “foundational” to its next set of cancer therapies, according to Andres Sirulnik, head of translational and clinical sciences in its hematology division.
But Regeneron has a tough road ahead. The medicines are among a growing list of dual-targeting medicines known as bispecific antibodies in clinical development for lymphomas and multiple myeloma. One medicine from Roche, known as Lunsumio, has already been approved in Europe and could be cleared in the U.S. later this month. Another, the multiple myeloma drug Tecvayli from Johnson & Johnson, was OK’d by U.S. regulators in October. Others from Pfizer and Bristol Myers Squibb are advancing through testing and a drug from AbbVie and Genmab is currently under FDA review.
The fierce competition has analysts skeptical of Regeneron’s sales prospects. While odronextamab is likely headed for an approval, the drug is “unlikely to be a groundbreaking treatment or dramatic revenue driver” unless Regeneron “can find creative ways to further improve its positioning,” wrote RBC Capital Markets analyst Brian Abrahams on Monday.
Safety is a concern, too, as regulators have previously halted testing of odronextamab. Regeneron has tweaked its dosing schedule to reduce side effects.
“It’s a very crowded space,” Sirulnik said. “The question is who's going to make a big dent and help patients?”
Development of these medicines has been closely watched in recent years because they could be more convenient and safer alternatives to therapies known as CAR-T, which are personalized treatments made from a patient’s own cells. While CAR-T treatments can drive blood cancers into long-lasting remissions, access is largely limited to large treatment centers and production can take weeks — time that patients with fast-moving malignancies might not have.
Emerging results show these drugs’ potential. In an editorial published Sunday in The New England Journal of Medicine, Nancy Bartlett, an oncology professor at the Washington University School of Medicine, noted the remission rates seen in testing of another Roche drug called glofitamab rivals the durable responses seen with CAR-T in large B-cell lymphoma.
Though many questions still need to be answered, Bartlett wrote, bispecifics “will be an excellent option” for patients who don’t respond to second-line CAR-T treatment and potentially “considered as the initial choice” for second- or third-line care.
Regeneron hopes its medicines will be one of those options. According to Sirulnik, Regeneron’s plan is to first get its foot in the door in late-line settings, and then develop combinations that can boost their potency while running tests in earlier treatment. That’s a strategy that chief scientific officer George Yancopoulos, acknowledging the competition, described on a November earnings call.
“The future is going to be about moving into earlier lines of therapy,” Yancopoulos said on the call, noting “there is going to be a lot of art” to designing those trials.
But Regeneron needs initial approvals first, and the ASH data could help it get closer.
In a Phase 2 trial of odronextamab in follicular lymphoma, investigators reported a roughly 82% response rate among 121 evaluable patients after a median of 22.4 months. Three-quarters of participants went into remission. Regeneron believes those numbers set “a new benchmark” in follicular lymphoma, Sirulnik said. About 72% of those remissions lasted at least 12 months, and 59% of them extended out through 18 months.
In another study, meanwhile, just under half of 130 evaluable patients with diffuse large B-cell lymphoma responded, with about a third in remission after a median of just over 21 months. Some two-thirds of those remissions were ongoing after a year and 48% lasted a year and a half.
Yet that efficacy comes with safety worries. Regeneron has changed odronextamab’s dosing in an attempt to lower rates of a potentially dangerous immune response called cytokine release syndrome that’s associated with the therapy and other drugs like it. There were fewer instances of moderate or severe CRS in patients on the newer regimen. But five DLBCL patients and three follicular lymphoma patients died from treatment-related adverse events. Many were from infections that Sirulnik noted are often seen in patients with advanced lymphoma.
Abrahams, of RBC, called odronextamab “reasonably competitive” with Roche and AbbVie’s drugs, though those medicines may be more convenient. AbbVie’s epcoritamab is administered through a subcutaneous injection and Roche’s drug has a less complicated dosing regimen, he wrote.
For linvoseltamab, 64% of the 58 multiple myeloma patients who received the dose Regeneron chose for the Phase 2 portion of its trial responded to treatment. About half had what investigators described as a “very good” response or better. There were few instances of severe CRS, but Regeneron did report other blood-related side effects that were considered severe.
These results are from single-arm studies, meaning the Regeneron’s drugs weren’t compared to a placebo or another treatment. They may be enough to support accelerated approval applications, though the Food and Drug Administration, which has more closely scrutinized speedy clearances of late, is now requiring controlled, confirmatory studies be “well underway” first, Sirulnik said.
Regeneron recently delayed its filing timeline as a result. The company expects to submit an application for odronextamab in the second half of 2023. (Linvoseltamab is earlier in development.) That means the drugs will likely be well behind those from Roche and J&J, just as Libtayo reached market long after other, similar immunotherapies.
As with Libtayo, Regeneron is staying the course.
“It's a long road,” Sirulnik acknowledged. But the two drugs, and others the company is advancing behind it “may put us in the frontline to potentially get a win for patients.”