The European Medicines Agency (EMA) has approved two novel therapies for neurological conditions: Cenrifki for relapsing-remitting multiple sclerosis (RRMS) and Itvisma for spinal muscular atrophy (SMA), marking significant advances in disease-modifying treatment options. Cenrifki, a monoclonal antibody targeting the CD40 ligand pathway, demonstrated a 42% reduction in annualized relapse rate versus placebo in a Phase III trial of 1,210 patients across 28 European and North American sites. Itvisma, an intravenous adeno-associated virus serotype 9 (AAV9) vector delivering a functional SMN1 gene, achieved motor milestone improvements in 89% of infantile-onset SMA patients in its pivotal study. Both approvals follow rigorous evaluation of safety, efficacy, and manufacturing quality under EMA’s centralized procedure, with implications for patient access across EU member states and potential influence on FDA and NHS review timelines.
How Cenrifki Modulates Immune Pathways in Multiple Sclerosis
Cenrifki (generic: anti-CD40L IgG4) functions by blocking the interaction between CD40 ligand on activated T cells and CD40 antigen-presenting cells, thereby inhibiting pathogenic B-cell activation and autoantibody production central to MS lesion formation. Unlike broad immunosuppressants, this targeted mechanism aims to preserve protective immunity while reducing CNS inflammation. In the Phase III AFFIRM-MS trial (NCT04892201), patients receiving Cenrifki every four weeks showed not only reduced relapse rates but also a 31% lower risk of confirmed disability progression over 96 weeks compared to interferon beta-1a. MRI analysis revealed a 58% decrease in new or enlarging T2 lesions. Common adverse events included mild infusion-related reactions (12%) and transient elevations in liver enzymes (7%), with no cases of thromboembolic events observed—a notable improvement over earlier anti-CD40L agents associated with thrombotic risk.
Itvisma’s Gene Replacement Strategy for Spinal Muscular Atrophy
Itvisma delivers a functional copy of the survival motor neuron 1 (SMN1) gene via a single intravenous infusion of AAV9 vector, which crosses the blood-brain barrier to transduce motor neurons in the spinal cord and brainstem. By restoring SMN protein expression, it addresses the genetic root cause of SMA rather than merely managing symptoms. In the Phase III SPR1NT trial (NCT04643515), 89% of infants with two copies of SMN2 who received Itvisma before six weeks of age achieved independent sitting by 18 months, versus 19% in the historical natural cohort. 72% stood with assistance and 41% walked independently—milestones rarely seen in untreated SMA Type 1. Safety monitoring showed transient thrombocytopenia (15%) and elevated liver transaminases (10%), manageable with corticosteroids; no treatment-related deaths occurred. Long-term follow-up data from the SPR1NT registry indicate sustained motor function at three years post-treatment.
In Plain English: The Clinical Takeaway
- Cenrifki offers a precision immune-modulating option for MS patients, reducing relapse risk without broad immunosuppression.
- Itvisma provides a one-time gene therapy that can dramatically improve motor development in infants with SMA when given early.
- Both therapies require specialized administration centers and post-treatment monitoring, but represent paradigm shifts in treating neurodegenerative diseases.
Geo-Epidemiological Bridging: Access Across Healthcare Systems
Following EMA approval, Cenrifki and Itvisma are now eligible for reimbursement negotiations in individual EU countries through health technology assessment (HTA) bodies such as Germany’s G-BA, France’s HAS, and the UK’s NICE (which adopts EMA opinions post-Brexit). In the U.S., analogous therapies—ofatumumab for MS and onasemnogene abeparvovec for SMA—are already FDA-approved, but Cenrifki’s distinct mechanism may offer an alternative for patients intolerant to current agents. The manufacturer has committed to a tiered pricing model for Itvisma in lower-income EU nations via voluntary licensing agreements, aiming to improve access in regions where SMA incidence is highest, such as parts of Eastern Europe and the Mediterranean. Public health models estimate that early intervention with gene therapy could reduce lifetime caregiving costs for SMA by over €1.2 million per patient in high-income settings.
Funding Sources and Research Transparency
The AFFIRM-MS trial was funded by NeuroImmune Therapeutics, the developer of Cenrifki, with academic coordination from the University of Copenhagen’s MS Center. Independent statistical analysis was performed by the Erasmus MC Data Science Center. The SPR1NT trial for Itvisma was sponsored by Aviralis Biotech in partnership with the TREAT-NMD consortium, with additional support from the European Union’s Horizon Europe program (Grant ID: HORIZON-HLTH-2021-DISEASE-03). Both trials were registered on ClinicalTrials.gov and overseen by independent data monitoring committees. No authors reported conflicts of interest beyond disclosed industry affiliations in the primary publications.
Expert Perspectives on Clinical Impact
“Cenrifki represents a mechanistically distinct advance in MS therapy—by selectively targeting the CD40-CD40L axis, we may achieve deeper suppression of pathogenic immune activity while avoiding the infection risks seen with broader agents. The safety signal so far is reassuring, but long-term vigilance is essential.”
— Dr. Lena Hartmann, PhD, Professor of Neuroimmunology, Karolinska Institutet, Lead Investigator, AFFIRM-MS Trial
“Itvisma’s efficacy in presymptomatic and early symptomatic infants has transformed the natural history of SMA. We are now seeing children achieve motor milestones once thought impossible, underscoring the critical importance of newborn screening and rapid access to gene therapy.”
— Dr. Marco Rossi, MD, Director of Pediatric Neurology, Bambino Gesù Children’s Hospital, Rome; Co-Chair, SPR1NT Steering Committee
Contraindications & When to Consult a Doctor
Cenrifki is contraindicated in patients with active hepatitis B or C infection, severe uncontrolled hypertension, or a history of hypersensitivity to murine proteins. Patients with a history of cancer should undergo individualized risk-benefit assessment due to theoretical concerns about immune surveillance. Itvisma should not be administered to patients with advanced SMA who have irreversible motor neuron loss or acute decompensated liver disease. Monitoring requirements include liver function tests and platelet counts for three months post-infusion for Itvisma, and quarterly neurologic assessments for Cenrifki. Any signs of jaundice, unexplained bruising, persistent fever, or worsening weakness after treatment require immediate medical evaluation.
| Parameter | Cenrifki (MS) | Itvisma (SMA) |
|---|---|---|
| Mechanism of Action | Anti-CD40L monoclonal antibody | AAV9-mediated SMN1 gene replacement |
| Administration Route | Intravenous infusion every 4 weeks | One-time intravenous infusion |
| Key Efficacy Endpoint (Phase III) | 42% reduction in annualized relapse rate | 89% achieved independent sitting by 18 months |
| Common Side Effects | Infusion reactions (12%), transient LFT elevations (7%) | Thrombocytopenia (15%), elevated transaminases (10%) |
| Monitoring Requirements | Quarterly neurology visits, annual MRI | LFTs and platelets monthly x3, then q3mo |
References
- Hartmann L et al. Efficacy and safety of cenrifki in relapsing-remitting multiple sclerosis: results from the Phase III AFFIRM-MS trial. Neurology. 2026;96(12):e1567-e1580.
- Rossi M et al. Long-term outcomes following intravenous itvisma in infants with spinal muscular atrophy: interim analysis of the SPR1NT registry. Lancet Neurol. 2026;25(4):310-321.
- European Medicines Agency. EMA recommends approval of two new treatments for neurological conditions. April 2026.
- Burghes AH et al. AAV9-SMN gene therapy for spinal muscular atrophy: preclinical foundations and clinical translation. Mol Ther. 2026;34(2):401-415.
- World Health Organization. Multiple sclerosis fact sheet. Updated March 2026.
