Mavenclad (cladribine) / EMD Serono - LARVOL DELTA

NICE recommends cladribine for treating active relapsing forms of multiple sclerosis (Pharm J) - "The National Institute for Health and Care Excellence (NICE) has expanded access to cladribine (Mavenclad; Merck) for adults with active relapsing-remitting multiple sclerosis (MS), if they would otherwise be offered highly effective disease-modifying drugs....The technology appraisal guidance, published on 15 April 2025, said that cladribine can be offered to people with MS as an alternative to Ocrevus (ocrelizumab; Roche Products) or Kesimpta (ofatumumab; Novartis) on the NHS....According to NICE’s evaluation committee, clinical trial evidence from the CLARITY and CLARITY-EXT trials shows that cladribine reduces relapses and increases the time until disability progresses compared with placebo."

NICE • Multiple Sclerosis

Serological screening and Vaccine Update in a cohort of Multiple Sclerosis Patients as a strategy to prevent infection reactivation during immunosuppressant therapy. (PubMed, Mult Scler Relat Disord) - "MS patients using immunosuppressant therapy may be susceptible to vaccine-preventable infectious diseases. The study demonstrates the feasibility of vaccine updates, and infectious diseases specialists can contribute assessing infection risks and providing individualized vaccines recommmendations."

Journal • CNS Disorders • Cytomegalovirus Infection • Hepatitis B • Hepatology • Herpes Zoster • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Influenza • Measles • Meningococcal Infections • Multiple Sclerosis • Mumps • Novel Coronavirus Disease • Pertussis • Pneumococcal Infections • Respiratory Diseases • Rubella • Tetanus • Varicella Zoster

Cladribine Tablets Level of Response Predictors in Clinical Practice (CLODINA) (clinicaltrials.gov) - P=N/A | N=360 | Active, not recruiting | Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2028 ➔ Jan 2029 | Trial primary completion date: Aug 2028 ➔ Jan 2029

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

A Study of Suboptimally Controlled Participants Previously Taking Oral or Infusion DMDs for RMS (MASTER-2) (clinicaltrials.gov) - P=N/A | N=291 | Completed | Sponsor: EMD Serono Research & Development Institute, Inc. | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Nov 2024 | Trial primary completion date: May 2025 ➔ Nov 2024

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Extended Follow Up Data on the Efficacy and Safety of Cladribine for Multiple Sclerosis in a Greater London Hospital (P12-1.009). (PubMed, Neurology) - "Dr. Mattoscio has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MERCK SERONO."

Journal • Retrospective data • CNS Disorders • Infectious Disease • Multiple Sclerosis

Concurrent Multiple Sclerosis and Primary Sclerosing Cholangitis Treated with Oral Cladribine (P12-1.008). (PubMed, Neurology) - "She was diagnosed with MS and started on glatiramer acetate...Ursodeoxycholic acid therapy did not result in any symptom improvement...Rodrigo Naves has nothing to disclose. Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff."

Journal • CNS Disorders • Dermatology • Fatigue • Fibrosis • Hepatology • Immunology • Multiple Sclerosis • Pain • Pruritus • Transplantation

Erdheim-Chester disease associated with Langerhans cell histiocytosis: A case of a mixed form (PubMed, Rev Med Interne) - "We report an observation of a mixed form of histiocytosis associating Langerhans cell histiocytosis and Erdheim-Chester disease, with a diagnostic delay of ten years, and having responded well to treatment with cladribine."

Journal • Cardiovascular • CNS Disorders • Dermatitis • Dermatology • Hematological Malignancies • Hypertension • Immunology • Langerhans Cell Histiocytosis • Metabolic Disorders • Oncology • Rare Diseases • Seborrheic Dermatitis

Assessment of Real-World Adverse Events Associated with Ozanimod in Relapsing Remitting Multiple Sclerosis (RRMS) (ISPOR 2025) - "AE reports and patient outcomes were extracted for all instances where DMTs (ozanimod, dimethyl fumarate, monomethyl fumarate, diroximel fumarate, fingolimod, ponesimod, siponimod, teriflunomide, cladribine, alemtuzumab, natalizumab, ocrelizumab, ublituximab, and ofatumumab) were the 'primary suspect' for the AE... Based on this descriptive analysis of the FAERS data, ozanimod has a lower proportion of AEs linked to serious outcomes than the other DMTs. Ozanimod generally had a larger share of the ten labeled AEs compared with the other DMTs; however, these labeled AEs made up a small percentage of all the AEs reported for ozanimod and the other DMTs."

Adverse events • Clinical • Real-world • Real-world evidence • Back Pain • Cardiovascular • CNS Disorders • Hypertension • Hypotension • Infectious Disease • Multiple Sclerosis • Musculoskeletal Pain • Pain • Respiratory Diseases

BONE MARROW HEMOPOIESIS IN PRE-TREATED MULTIPLE SCLEROSIS BEFORE AUTOLOGOUS STEM CELL TRANSPLANTATION (EBMT 2025) - "A 6-month wash-out from anti-CD20 and 1,5 months from cyclophosphamide (cy) to harvest was performed. No differences in BM populations were observed between pre-treated MSp and HS, although the comparison was limited by the small number of HS and lack of matching for age and sex. The slight decrease of M in favour of MP in MSp can be explained by transient neutropenia induced by previous treatments (cy, cladribine) with subsequent BM recovery through expansion of MP. Although our data are not directly comparable with the study by Shi et al because of pre-test mature red blood cells lysis, we did not find in a broader MSp population neither increased myeloid expansion and commitment nor decreased MSC suggesting that MS treatments can directly or indirectly affect BM cellular populations.Furthermore, no significant differences in median B lymphocyte count were observed, irrespective of previous treatments, likely reflecting the efficacy of anti-CD20 and Cy wash-out in..."

Bone Marrow Transplantation • CNS Disorders • Hematological Disorders • Hematological Malignancies • Multiple Sclerosis • Myelodysplastic Syndrome • Neutropenia • Oncology • Transplantation • CD34

BONE MARROW HEMOPOIESIS IN PRE-TREATED MULTIPLE SCLEROSIS BEFORE AUTOLOGOUS STEM CELL TRANSPLANTATION (EBMT 2025) - "A 6-month wash-out from anti-CD20 and 1,5 months from cyclophosphamide (cy) to harvest was performed. No differences in BM populations were observed between pre-treated MSp and HS, although the comparison was limited by the small number of HS and lack of matching for age and sex. The slight decrease of M in favour of MP in MSp can be explained by transient neutropenia induced by previous treatments (cy, cladribine) with subsequent BM recovery through expansion of MP. Although our data are not directly comparable with the study by Shi et al because of pre-test mature red blood cells lysis, we did not find in a broader MSp population neither increased myeloid expansion and commitment nor decreased MSC suggesting that MS treatments can directly or indirectly affect BM cellular populations.Furthermore, no significant differences in median B lymphocyte count were observed, irrespective of previous treatments, likely reflecting the efficacy of anti-CD20 and Cy wash-out in..."

Bone Marrow Transplantation • CNS Disorders • Hematological Disorders • Hematological Malignancies • Multiple Sclerosis • Myelodysplastic Syndrome • Neutropenia • Oncology • Transplantation • CD34

Effect of Cladribine Tablets on the Pharmacokinetics of a Combined Oral Contraceptive in Pre-Menopausal Women With Relapsing Multiple Sclerosis. (PubMed, Clin Transl Sci) - "Repeat-dose administration of CladT had no apparent effect on serum luteinizing hormone, follicle-stimulating hormone, progesterone, or sex hormone-binding globulin concentrations during concomitant treatment with COC. Therefore, the concomitant use of CladT is not expected to decrease the efficacy of COCs containing EE and LNG. Trial Registration: EudraCT Number: 2018-001015-70."

Clinical • Journal • PK/PD data • CNS Disorders • Multiple Sclerosis

Recommendations for essential medicines for multiple sclerosis in low-resource settings. (PubMed, Mult Scler) - "Recommendations for the minimum essential DMTs for MS in low-resource settings were developed based on robust consideration of evidence and relevant context."

Journal • CNS Disorders • Multiple Sclerosis

First insights into the safety and effectiveness of additional courses with cladribine tablets under real-world conditions. (PubMed, Mult Scler Relat Disord) - "Administering additional cladribine courses is an effective option to maintain disease control and did not trigger any serious adverse events attributable to the therapy. Patients with elevated serum transaminase levels should be regularly monitored."

Journal • Real-world evidence • CNS Disorders • Multiple Sclerosis

CLADREXIT: Cladribine Tablets as an Exit Therapy Strategy (clinicaltrials.gov) - P=N/A | N=450 | Not yet recruiting | Sponsor: University Hospital, Strasbourg, France

New trial • CNS Disorders • Multiple Sclerosis

European experience of cladribine tablets in elderly patients with multiple sclerosis: Could it be the last treatment? (PubMed, Mult Scler J Exp Transl Clin) - "The first one had 2 relapses after switching from fingolimod with a 2-month interval between treatments. The 2 remaining were naïve patients that had a relapse between the 2 courses of CladT. Last/exit therapy with CladT seems to avoid MS disease reactivation in older PWMS and may be an interesting alternative solution to continue immunosuppression/immunomodulation."

Journal • CNS Disorders • Immunology • Multiple Sclerosis

Cladribine Is Associated With Stable Cortical Gray Matter Lesion Burden in Multiple Sclerosis: A 7T MRI Study. (PubMed, J Neuroimaging) - "These observational data suggest that cladribine therapy stabilizes cortical demyelination in MS over the first year of treatment. Overall, LME burden remained stable over 1 year; however, within-subject resolution and accrual were noted."

Journal • CNS Disorders • Multiple Sclerosis

Long-Term Management and Therapeutic Sequencing for Patients with Relapsing Multiple Sclerosis in France: A Vignette Study. (PubMed, Neurol Ther) - "These findings suggest that the management of RMS in France has shifted in recent years towards a desire to achieve earlier and more effective control of disease activity for people with RMS. Better guidance on the sequencing of DMTs for different scenarios within the overall management of RMS may be warranted. This study offers valuable insights into the current practices of French neurologists in managing RMS, emphasizing the complexity of therapeutic decisions, the diversity of strategies, and the significance of an individualized approach in treatment management."

Journal • CNS Disorders • Multiple Sclerosis

cladribine (Mavenclad) (Scottish Medicines Consortium) - "Indication: Treatment of adult patients with relapsing forms of multiple sclerosis (RMS) with active disease as defined by clinical or imaging features; Submission type: Full"

Reimbursement • Multiple Sclerosis

MS patients in England to benefit from major roll out of take-at-home pill (Guardian) - "Thousands of patients with multiple sclerosis (MS) in England are to become the first in Europe to benefit from a major roll out of an immunotherapy pill...The new tablet, cladribine, can be swallowed at home, and needs to be taken only 20 times in the first two years of a four-year cycle. The regime consists of a maximum of 10 days of treatment in the first year and 10 days in the second; no additional treatment is needed in the next two years...The NHS in England is the first healthcare system in Europe to widely introduce the drug to patients with active relapsing-remitting MS after it received the go-ahead from the National Institute for Health and Care Excellence (Nice)....It was previously approved only for patients with more severe, highly active MS, but cladribine, made by Merck, will now be available to many more patients."

NICE • Multiple Sclerosis

The gut-brain-axis one year after treatment with cladribine tablets in patients with relapsing remitting multiple sclerosis: a pilot study. (PubMed, Front Immunol) - "Overall, we showed that we can measure a treatment effect from cladribine tablets with our analyses. Future research on data from the BIA study, with a larger sample size and extended follow-up, can possibly confirm the reliability of our findings."

Journal • Observational data • CNS Disorders • Multiple Sclerosis • B3GAT1

Assessment of the impact of reconstitution therapies-cladribine tablets and alemtuzumab-on the atrophy progression among patients with relapse-remitting multiple sclerosis. (PubMed, Front Neurosci) - "The study was limited by the small number of both groups. Therefore, further studies are needed to fully assess the effect of reconstitution therapies on neurodegenerative processes in patients with RRMS."

Journal • CNS Disorders • Multiple Sclerosis

Herpes Zoster Infections With Multiple Sclerosis Disease-Modifying Therapies: A Real-World Pharmacovigilance Study. (PubMed, Neurol Clin Pract) - "We queried the Food and Drug Administration Adverse Event Reporting System (FAERS) and OpenVigil 2.1 for reports of HZ involving immunosuppressive MS DMTs (ocrelizumab [OCR], ofatumumab [OFT], rituximab [RTX], natalizumab [NTZ], alemtuzumab, dimethyl fumarate and diroximel fumarate [DRF], fingolimod [FING], siponimod [SIP], ozanimod [OZ], mitoxantrone [MITO], cladribine [CLAD], and teriflunomide [TERF]) and calculated reporting odds ratios and their 95% CIs...Immunosuppressive MS DMTs are associated with greater HZ reporting in the FAERS. These findings emphasize the importance of pre-DMT HZ vaccination because of avoidable HZ infections."

Adverse events • Journal • Real-world evidence • CNS Disorders • Herpes Zoster • Infectious Disease • Multiple Sclerosis • Varicella Zoster

ChariotMS - Cladribine to Halt Deterioration in People With Advanced Multiple Sclerosis (clinicaltrials.gov) - P2/3 | N=200 | Recruiting | Sponsor: Queen Mary University of London | Trial primary completion date: Dec 2024 ➔ Dec 2027

HEOR • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Real-world Treatment Outcomes in People with Multiple Sclerosis Switched from Platform MS Treatments to Fumarates Versus Other Oral Disease-modifying Therapies (AAN 2025) - "Objective:Assess the real-world effectiveness of fumarates (FUM) compared to sphingosine 1-phosphate receptor modulators (S1Ps) and cladribine (CLAD) in people with multiple sclerosis (MS) switching from platform MS disease-modifying therapies (DMTs) by evaluating annualized relapse rates (ARR), healthcare resource utilization (HCRU), and healthcare costs (HCC).Background:MS is a chronic autoimmune disease causing significant morbidity and healthcare utilization...In MS patients switching from platform therapies, FUM provides similar effectiveness and HCRU compared to S1Ps and CLAD."

Clinical • HEOR • Real-world • Real-world evidence • CNS Disorders • Immunology • Multiple Sclerosis

From Trials to Real-world Data: National Insights on Cladribine Tablets in Multiple Sclerosis After Four Years and Beyond (AAN 2025) - "Most PwMS do not require additional treatment 4-5 years after initiating cladribine tablets, despite not being treatment-naïve like majority in the CLARITY trial. Retreatment appears to be a beneficial strategy for less stable patients, but further FU is needed to assess its long-term efficacy."

Clinical • Real-world • Real-world evidence • CNS Disorders • Multiple Sclerosis