Regeneron's LINKER-MM2 Trial Shakes Up Multiple Myeloma Treatment: A New Paradigm Emerges for Oncology Investors

The multiple myeloma treatment landscape is on the cusp of a transformation, and Regeneron's linvoseltamab may be the catalyst. Recent data from the Phase 1b LINKER-MM2 trial, presented at the 2025 ASCO Annual Meeting, underscores the drug's potential to redefine care for relapsed/refractory (R/R) patients while bolstering Regeneron's oncology pipeline valuation.

Efficacy: A Breakthrough in a Challenging Setting

The trial tested linvoseltamab in combination with proteasome inhibitors (PIs) carfilzomib or bortezomib in patients with heavily pretreated R/R multiple myeloma. Key efficacy metrics are staggering:
- Carfilzomib combo: In 21 evaluable patients, 90% achieved an objective response (ORR), with 76% attaining a complete response (CR). At 12 months, 87% maintained response, and 83% remained progression-free.
- Bortezomib combo: 85% ORR, including 50% CR, with median follow-up of 9 months.

These outcomes are particularly notable given the high-risk patient population: all had prior PI exposure, 52% had soft tissue plasmacytomas, and nearly 40% were over 75—a group often excluded from trials due to frailty. The results suggest linvoseltamab could fill a critical gap in earlier lines of therapy, potentially shifting treatment paradigms away from salvage regimens to more aggressive combinations earlier in the disease course.

Safety: Balancing Risks with Rewards

While efficacy is compelling, safety data requires careful consideration. Both combinations carried significant hematologic toxicities (neutropenia, thrombocytopenia) and infections (up to 91% in the carfilzomib arm), though severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were rare (0% Grade ≥3 in carfilzomib combo).

Investors should note that these risks are not uncommon in myeloma therapies targeting CD3, but Regeneron's step-up dosing and careful management of toxicities (e.g., one DLT of tumor lysis syndrome) suggest a manageable profile. The lack of Grade ≥3 CRS or ICANS in the carfilzomib arm is a positive signal compared to other bispecifics.

Regulatory and Commercial Momentum

Linvoseltamab is already approved in the EU for later-line R/R myeloma (as Lynozyfic™), and the FDA's review of the U.S. BLA is nearing its July 10, 2025, PDUFA date. The Phase 3 trial, which will compare the carfilzomib combo to standard-of-care in the same population, is poised to solidify linvoseltamab's role in earlier lines.

With an estimated global myeloma market exceeding $10 billion by 2030—and linvoseltamab's potential to expand into earlier lines—the drug's peak sales could approach $2–3 billion annually. This positions Regeneron's oncology pipeline as a rare growth engine in an increasingly crowded space.

Pipeline Valuation: A Strategic Asset

Regeneron's oncology portfolio has long been overshadowed by its eye care and inflammation assets, but linvoseltamab's success could reshape perceptions. The drug's BCMA-CD3 mechanism targets a validated pathway, and its combination flexibility with existing therapies (e.g., PIs, anti-CD38 antibodies) could enable broader label expansions.

Competitors like AbbVie's venetoclax and other BCMA-targeting bispecifics (e.g., Janssen's teclistamab) face limitations in response depth or toxicity. Linvoseltamab's CR rates and manageable safety profile may give it an edge in real-world adoption, especially if Phase 3 confirms the durability seen in Phase 1b.

Investment Thesis: Act Now, Before the FDA Rules

With linvoseltamab's EU approval and the FDA's decision looming, Regeneron stands at a pivotal moment. The stock has underperformed peers in recent quarters, but the LINKER-MM2 data could catalyze a revaluation. Key catalysts ahead include:
1. FDA Approval (July 2025): A green light would unlock immediate U.S. sales and provide runway for Phase 3 data.
2. Phase 3 Trial Readout: Positive results could support earlier-line indications and expanded use.

Investors should also consider the broader oncology landscape: as therapies move from late-line to earlier settings, the first-mover advantage matters. Linvoseltamab's data suggests it could claim that position.

Conclusion: A Paradigm Shift with Immediate Implications

The LINKER-MM2 trial marks a turning point in multiple myeloma treatment, offering high-response rates and manageable safety in a population with limited options. Regeneron's oncology pipeline, once a secondary focus, now harbors a transformative asset. With regulatory milestones imminent and a robust commercial path forward, the time to act is now—before the market fully prices in linvoseltamab's potential.

For investors seeking exposure to a breakthrough therapy with scalable commercial upside, Regeneron's stock presents a compelling opportunity. The question isn't whether linvoseltamab will redefine myeloma care—it's whether you're positioned to capitalize on it.