Regeneron and Sanofi's Alzheimer's Pipeline: Navigating EU Regulatory Momentum and Market Capture Potential

In the high-stakes race to develop effective Alzheimer's therapies, Regeneron and Sanofi stand at a pivotal inflection point. While their Alzheimer's pipeline lacks direct ties to Kymriah—a CAR-T therapy for cancer—their recent strategic moves and regulatory engagements signal a recalibration of focus toward neurodegenerative disease. With the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) demonstrating a nuanced approach to Alzheimer's approvals in 2025, the duo's candidates—Sanofi's TREM2 agonist VG-3927 and Regeneron's RNAi therapeutic ALN-APP—are poised to capitalize on a shifting regulatory landscape and a $30 billion marketAlzheimer’s disease drug development pipeline: 2025^[1].

Regulatory Momentum: CHMP's Evolving Stance

The CHMP's 2025 decisions reveal a cautious yet adaptive framework. After initially rejecting Kisunla (donanemab) due to amyloid-related imaging abnormalities (ARIA), the committee revised its stance in July 2025, recommending approval for a restricted patient populationEMA Committee Recommends Kisunla for …^[2]. Similarly, Leqembi (lecanemab) faced rejection in March 2025 but secured conditional approval in April 2025 after Eisai and Biogen addressed safety concernsEuropean Commission approves first disease-modifying treatment …^[3]. These reversals underscore the EMA's willingness to balance risk with unmet medical need—a dynamic that could benefit Sanofi and Regeneron.

For Sanofi, the acquisition of Vigil Neuroscience in August 2025 for $470 million (plus a contingent value right) added VG-3927, a novel oral TREM2 agonist targeting microglial activationSanofi Acquires Vigil Neuroscience to Advance VG-3927 Alzheimer’s Program and Expand Neurodegeneration Research^[4]. Early Phase 1 data demonstrated favorable pharmacokinetics and CNS penetration, with Phase 2 trials slated for late 2025VG-3927 | ALZFORUM^[5]. Unlike amyloid-targeting therapies, VG-3927 addresses neuroinflammation—a pathway increasingly linked to Alzheimer's progressionVigil Neuroscience Presents Data on its Small Molecule TREM2 Agonist VG-3927 in Two Oral Presentations at AD/PD 2025 International Conference^[6]. This differentiation could position it for CHMP scrutiny akin to Leqembi's revised approval, particularly if Phase 2 results show robust cognitive benefits with manageable safety profiles.

Regeneron's ALN-APP, an RNAi therapeutic targeting amyloid precursor protein (APP), has also shown promise. Interim Phase 1 results revealed up to 90% reductions in soluble APP biomarkers in cerebrospinal fluid, with no severe adverse eventsRegeneron and Alnylam Report Positive Interim Phase 1 Clinical Data on ALN-APP, an Investigational RNAi Therapeutic for Alzheimer’s Disease and Cerebral Amyloid Angiopathy^[7]. While the FDA placed a partial clinical hold on further trials due to non-clinical findings, Regeneron and Alnylam have secured approval to proceed in CanadaAlnylam’s early Alzheimer’s results encourage, but company faces FDA hold^[8]. The CHMP's recent flexibility with Leqembi and Kisunla suggests a potential pathway for ALN-APP, especially if the companies address safety concerns and demonstrate long-term efficacy.

Market Capture Potential: A $30 Billion Opportunity

The EU's Alzheimer's market, though smaller than the US, represents a critical battleground. With Leqembi and Kisunla already generating $2 billion in combined global salesFive years, one approval: Europe’s slow march on Alzheimer’s …^[9], Sanofi and Regeneron's candidates could carve out significant market share. VG-3927's oral formulation and novel mechanism offer a distinct advantage over injectable amyloid-targeting therapies, while ALN-APP's CNS gene-silencing approach could redefine treatment paradigms.

However, challenges persist. The CHMP's emphasis on risk mitigation—evident in Leqembi's restricted labeling for ApoE4-negative patients—means Sanofi and Regeneron must navigate stringent post-marketing requirements. For instance, VG-3927's Phase 2 trials will need to incorporate biomarker-driven patient stratification to align with EMA expectationsSanofi completes the acquisition of Vigil Neuroscience, Inc.^[10]. Similarly, ALN-APP's long-term safety data will be scrutinized, particularly given the EMA's rejection of Kisunla over ARIA risksEurope's CHMP turns down Lilly's Alzheimer's drug …^[11].

Strategic Implications for Investors

The EMA's proposed new guideline on Alzheimer's therapies, expected in late 2025, could further accelerate approvals for innovative mechanisms like TREM2 agonism or RNAiEMA proposes updating guideline for Alzheimer's …^[12]. This regulatory tailwind, coupled with Sanofi's and Regeneron's deep pockets and collaborative ecosystems, positions them to outmaneuver smaller biotechs. For investors, the key catalysts will be:
1. Phase 2 results for VG-3927 (Q4 2025): Positive data could trigger a CHMP filing by 2026.
2. ALN-APP's resolution of FDA/EMA concerns: A successful Phase 2 readout or risk-mitigation strategy could unlock EU and global expansion.
3. EMA's final decision on Kisunla (Q3 2025): A positive outcome would validate the pathway for similar therapies, boosting confidence in Sanofi and Regeneron's candidates.

Conclusion

While the EU's regulatory environment remains conservative, the CHMP's 2025 decisions signal a pragmatic shift toward accepting risk-benefit trade-offs for Alzheimer's therapies. Sanofi's VG-3927 and Regeneron's ALN-APP, with their novel mechanisms and strategic positioning, are well-placed to capture this momentum. For investors, the coming months will test the companies' ability to navigate safety concerns and regulatory nuance—but the potential rewards, in both market share and shareholder value, are substantial.