ASH: Regeneron makes frontline case for Lynozyfic in myeloma

Regeneron has been a bit of a latecomer in the market for BCMA-directed therapies for multiple myeloma, but is pushing to catch up with rival therapies from Johnson & Johnson and Pfizer.

The company's BCMAxCD3 bispecific antibody Lynozyfic (linvoseltamab) got its first FDA approval as a fifth-line or later therapy for relapsed/refractory multiple myeloma in the summer – around two years after J&J's Tecvayli (teclistamab) and Pfizer's Elrexfio (elranatamab), its two closest rivals in the anti-BCMA category.

At ASH, Regeneron made the case to move Lynozyfic into the previously untreated multiple myeloma setting with the results of the phase 1/2 LINKER-MM4 study, which tested three doses of the bispecific. The headline result is a 70%-plus very good partial response or better (VGPR+) rate with the drug and a high, 95% rate of minimum residual disease (MRD) negativity.

According to Regeneron, LINKER-MM4 is the first clinical trial to evaluate a BCMAxCD3 bispecific monotherapy in treatment-naïve multiple myeloma, which lead investigator Robert Orlowski of MD Anderson Cancer Center said was an impressive result, given that most newly diagnosed patients are often treated with "complicated combinations of quadruplet or triplet regimens, each with its own toxicities."

That makes LINKER-MM4 an important study, even if it also shows that combinations will be required to drive response rates up towards 100%, as not all patients are able to tolerate more aggressive treatment. The study included both transplant-eligible and transplant-ineligible patients.

"Lynozyfic monotherapy is already achieving MRD negativity rates comparable to quadruplet regimens, but earlier in the treatment course, and these compelling results are expected to deepen with longer follow-up," said Orlowski.

The new study is one of several Regeneron is running to expand the label for Lynozyfic across newly-diagnosed and relapsed/refractory multiple myeloma – including in combination with other drugs – and catch up with its rivals in the BCMA-directed class.

Those also feature GSK's relaunched antibody-drug conjugate Blenrep (belantamab mafodotin), as well as well-established CAR-T therapies from Bristol Myers Squibb and J&J/Legend Biotech.

Regeneron hopes Lynozyfic will be able to stand out thanks to its "patient-centric response-adapted dosing regimen," which requires infusions every two weeks after an initial induction period, and every four weeks in patients who have a very good partial response (VGPR) after 24 weeks.

In contrast, Tecvayli and Elrexfio and given as subcutaneous injections by healthcare professionals, initially once a week after induction and subsequently every other week if deemed appropriate. Blenrep, meanwhile, is administered as an IV infusion every three weeks.