This Neuroscience update covers clinical readouts, regulatory actions, biomarker advances, biosimilar access shifts, and neurodegeneration pipelines shaping multiple sclerosis, Alzheimer’s disease, and broader neuroscience innovation.
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💊 PIPE-307 Phase 2 in RRMS misses primary [1] [22 Dec 2025]
Context: VISTA Phase 2, 168 RRMS patients, 30 weeks, binocular 2.5% LCLA primary endpoint.
Key point: PIPE-307 did not meet the prespecified primary endpoint; company will analyze exploratory endpoints.
Implication: May influence prescriber choice and payer reviews pending full data.
🤖 AI identifies two biological MS subtypes via MRI+sNfL [2] [31 Dec 2025]
Context: ~600 MS patients, SuStaIn model, serum NfL plus MRI.
Key point: “Early sNfL” vs “late sNfL” profiles suggest differing disease aggressiveness.
Implication: Could inform practice and payer discussions, interpretation depends on study design and confounding control.
✅ NICE backs natalizumab for highly active RRMS, incl. biosimilar [3] [02 Jan 2026]
Context: Adults with highly active RRMS after ≥1 DMT when cladribine unsuitable; Tysabri (SC) and Tyruko (IV).
Key point: Guidance adds pregnancy-suitable option and widens access.
Implication: Introduces competition that may affect pricing and formulary access.
🧪 Immune signal ratio linked to progressive MS inflammation [4] [02 Jan 2026]
https://neurosciencenews.com/immune-signal-multiple-sclerosis-30080/
Context: Summary of Nature Immunology work on leptomeningeal inflammation and BTK inhibitor effects in mice.
Key point: Elevated CXCL13:BAFF associated with compartmentalized inflammation in progressive MS.
Implication: Could inform practice and payer discussions, interpretation depends on study design and confounding control.
🧬 Tyruko (natalizumab-sztn) US availability announced [5] [17 Dec 2025]
Context: Sandoz launch communication, FDA-approved for all Tysabri indications; REMS in place, Labcorp JCV testing support.
Key point: First US MS biosimilar offering a cost-effective natalizumab option.
Implication: Introduces competition that may affect pricing and formulary access.
🛑 FDA issues CRL for tolebrutinib in nrSPMS [6] [24 Dec 2025]
Context: nrSPMS NDA received CRL; EU and other reviews ongoing; expanded access protocol submitted at FDA request.
Key point: Sanofi expresses disappointment and plans to engage FDA on next steps.
Implication: May influence prescriber choice and payer reviews pending full data.
🧠 QALSODY (tofersen) long-term VALOR/OLE data published [7] [22 Dec 2025]
Context: JAMA Neurology publication, >3.5 years follow-up in SOD1-ALS.
Key point: Early initiation associated with numerically slower functional decline and reduced risk of death or permanent ventilation, with sustained neurofilament reductions.
Implication: May influence prescriber choice and payer reviews pending full data.
🧫 NurExone exosomes show anti-inflammatory activity in vitro [8] [19 Dec 2025]
Context: LPS-stimulated RAW 264.7 assay vs commercial exosomes; concentration-response reported.
Key point: Company reports reduced IL-6 and TNF-α vs control, outperforming comparator.
Implication: Could inform practice and payer discussions, interpretation depends on study design and confounding control.
⚡ Biohaven’s BHV-7000 fails Phase 2 in MDD [9] [02 Jan 2026]
Context: ~300-patient, 6-week study, Kv7.2/7.3 activator vs placebo.
Key point: No benefit on MADRS; psychiatry deprioritized while epilepsy program proceeds.
Implication: May influence prescriber choice and payer reviews pending full data.
🧓 AXS-05 for Alzheimer’s agitation gets FDA Priority Review [10] [31 Dec 2026]
Context: sNDA accepted with Priority Review; PDUFA action goal set.
Key point: Filing includes four randomized Phase 3 studies plus long-term safety.
Implication: May influence prescriber choice and payer reviews pending full data.
🔋 NAD+-restoring small molecule reverses AD phenotypes in mice [11] [02 Jan 2026]
Context: Cell Reports Medicine paper on P7C3-A20 in amyloid and tau models.
Key point: Improved memory and anxiety behaviors in advanced-stage AD mice; human AD tissue showed lower NAD+.
Implication: Could inform practice and payer discussions, interpretation depends on study design and confounding control.
🩸 Nature study maps AD pathology with pTau-217 blood test [12] [31 Dec 2025]
Context: >11,400 samples from Norway’s HUNT study; Quanterix Simoa pTau-217 assay.
Key point: Age-linked pathology prevalence with identification and rule-out utility for clinical planning.
Implication: Could inform practice and payer discussions, interpretation depends on study design and confounding control.
📒 Thermo Fisher launches CorEvitas AD Registry [13] [18 Dec 2025]
Context: International longitudinal registry, clinician-reported data, MRI safety monitoring.
Key point: Aims to generate regulatory-grade RWE on safety, patterns, plaque clearance and outcomes.
Implication: Could inform practice and payer discussions, interpretation depends on study design and confounding control.
🌱 Hope Biosciences MSCs in Parkinson’s show clinician-rated gains [14] [23 Dec 2025]
Context: Single-site Phase 2, 60 patients, six infusions over 32 weeks.
Key point: Reported MDS-UPDRS Part III improvement vs placebo; divergent patient-reported Part II not detailed.
Implication: Could inform practice and payer discussions, interpretation depends on study design and confounding control.
🧩 IRLAB starts Phase Ib of IRL757 for PD apathy [15] [23 Dec 2025]
https://finance.yahoo.com/news/irlab-receives-approval-phase-ib-070000864.html
Context: 75-patient signal-finding study across Germany, Bulgaria, Poland, Spain; funded by MSRD (Otsuka).
Key point: Prior Phase 1 in young and older adults showed good exposure and tolerability over 10 days.
Implication: Signals pipeline investment and modality expansion.
Why it matters
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Biomarkers, AI subtyping and RWE infrastructure are maturing in MS and AD, enabling stratified trials and earlier intervention.
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UK guidance and a US biosimilar expand natalizumab access, which can shift pricing and formulary dynamics.
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Regulatory actions in MS and AD reset timelines, while mixed CNS efficacy signals underscore the need for robust endpoints.
FAQ
What did Continuem report for PIPE-307 in RRMS?
PIPE-307 did not meet the Phase 2 VISTA primary endpoint on low-contrast letter acuity over 30 weeks; exploratory analyses are planned for publication [1].
How does NICE’s decision change MS care?
NICE recommended natalizumab for highly active RRMS after at least one DMT when cladribine is unsuitable, including Tysabri (SC) and Tyruko (IV), which broadens options and may aid pregnancy planning [3].
What is the CXCL13:BAFF ratio’s potential role in MS?
A higher ratio correlated with leptomeningeal inflammation linked to progressive MS, and BTK inhibitors normalized this ratio in mice. Clinical utility will depend on validation and prospective studies (endpoint not specified) [4].
What happened with tolebrutinib’s US filing?
FDA issued a CRL for nrSPMS; Sanofi plans to work with FDA while reviews continue in other regions [6].
What Alzheimer’s diagnostics and therapies advanced?
AXS-05 for AD agitation received FDA Priority Review with an action goal date set; Quanterix’s pTau-217 assay supported population-level detection in a Nature study; Thermo Fisher initiated a global AD registry to gather RWE [10][12][13].
Any notable ALS updates?
JAMA Neurology published long-term VALOR/OLE data where earlier QALSODY initiation was associated with numerically slower decline and reduced risk of death or permanent ventilation, with sustained neurofilament reduction [7].