Regeneron bets big on Lynozyfic

Regeneron’s Lynozyfic is behind in the BCMA-targeting T-cell engager race, but the group is pushing on, highlighting four new pivotal trials in its fourth-quarter presentation last week.

In particular, the company will begin a phase 3 study this year in high-risk smouldering multiple myeloma head to head versus Darzalex, the Johnson & Johnson and Genmab anti-CD38 antibody that recently received FDA approval in this setting. Notably, J&J doesn’t appear to be pursuing pivotal trials of its own BCMA T-cell engager, Tecvayli, in this use.

Instead, J&J has so far relied on investigator-sponsored trials of Tecvayli in smouldering multiple myeloma, namely the Immuno-Prism and Revive studies. Pfizer’s Elfexfio is also in an academic-led phase 2, called Erasmm, in this setting.

Transplant-eligible

Still, the big use for anti-BCMA T-cell engagers looks like being the front line, where all three companies are vying for a piece of the pie.

The new Lynozyfic trials, called Linker-MM7 and Linker-MM8, will both evaluate first-line transplant-eligible patients. The former will test monotherapy versus standard of care, while the latter will evaluate an as-yet-undisclosed combo versus autologous stem cell transplantation.

Regeneron hopes that minimal residual disease (MRD) negativity will be enough to support a filing, in line with new FDA guidance that supports this endpoint in early multiple myeloma lines.

MRD data are due from Linker-MM7 in 2028, and from Linker-MM8 in 2030, with PFS results expected in 2030 and 2032 respectively.

Regeneron appears to be taking a different approach from J&J, which with its Majestec-4 trial is testing Tecvayli (with or without Revlimid) in post-transplant patients. Pfizer also has a post-transplant study of Elrexfio, Magnetismm-7.

Magnetismm-7 completes in 2027, and Majestec-4 in 2028, potentially putting all three trials on a similar timeline.

Transplant-ineligible

Meanwhile, in newly diagnosed transplant-ineligible patients, Lynozyfic is already in an investigator-sponsored pivotal study, Linker-MM6, testing monotherapy versus Darzalex, Revlimid and dexamethasone.

Regeneron is again banking on MRD data, which are due in 2028.

And again the group’s approach differs from that of J&J and Pfizer, which are both testing Darzalex/Revlimid combos, J&J in the Majestec-7 study, and Pfizer in Magnetismm-6. The Magnetismm-6 trial completes in 2030, and Majestec-7 in 2031.

All this suggests that, in earlier lines at least, Lynozyfic could be catching up. Still, the next readout for Regeneron’s drug is expected next year from the Linker-MM3 trial in patients with one to four prior lines of therapy. The study is comparing monotherapy versus Empliciti, Pomalyst and dexamethasone.

Tecvayli has already produced positive results in the second-line plus setting, as part of a Darzalex combo in Majestec-3, and as monotherapy in Majestec-9, recently toplined as a success.

However, the latter study focused exclusively on post-Darzalex patients, while Linker-MM3’s clinicaltrials.gov entry only states that patients in the EU, UK and Israel must have received a prior anti-CD38 antibody.

Pfizer is also running two pivotal trials in relapsed/refractory multiple myeloma: Magnetismm-5 tests Elrexfio with or without Darzalex in double class-exposed disease; and Magnetismm-32 tests monotherapy in patients who have received one to four prior therapy lines, including an anti-CD38 MAb. Both are now due to complete this year, versus 2025 previously.

Ongoing and planned phase 3 trials of Lynozyfic in multiple myeloma

Notes: *MRD negativity expected to be registrational endpoint; **investigator-sponsored; ^ph2/3; ASCT=autologous stem cell transplant; D=Darzalex; d=dexamethasone; E=Empliciti; P=Pomalyst. Source: OncologyPipeline & company presentation.