Agamree (vamorolone) / ReveraGen, Santhera, Catalyst Pharma, Xoma - LARVOL DELTA

Health Canada Approves AGAMREE (vamorolone) as the First Treatment for Duchenne Muscular Dystrophy in Canada (PRNewswire) - "The Health Canada approval of AGAMREE was based on the data from the pivotal Phase 2b VISION-DMD study as supplemented with safety information collected from four open-label studies, including extension studies. In these trials, AGAMREE was administered at doses ranging from 2 to 6 mg/kg/day, extending for a period of up to 48 months."

Canada approval • Duchenne Muscular Dystrophy

A Study to Assess Vamorolone in Becker Muscular Dystrophy (BMD) (clinicaltrials.gov) - P2 | N=46 | Completed | Sponsor: ReveraGen BioPharma, Inc. | Active, not recruiting ➔ Completed

Trial completion • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Muscular Dystrophy

Mineralocorticoid receptor antagonism of vamorolone: Evidence from LIONHEART and VISION-DMD clinical trials. (PubMed, Steroids) - "In LIONHEART, 30 healthy adult males were randomized 1:1:1 to vamorolone 20 mg/kg, eplerenone 200 mg, or no treatment arms. A fludrocortisone challenge was administered between -9 h and 24 h after treatment...In VISION-DMD, boys with DMD aged 4-7 years were treated with vamorolone 2 or 6 mg/kg/d for 48 weeks or with prednisone 0.75 mg/kg/d or placebo for 24 weeks followed by vamorolone 2 or 6 mg/kg/d for 20 weeks following a 4-week washout...The VISION-DMD results showed vamorolone-specific increases in renin serum levels, as well as klotho, and calcium carrier proteins fetuin A and B, consistent with an MR antagonist effect. The available data confirm the MR antagonistic effect of vamorolone in humans."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Test-Retest Reliability of Motor Function and Myometry Outcomes From the Vamorolone Trials in Duchenne Muscular Dystrophy. (PubMed, Neurol Genet) - "We found NSAA, RWV, and CLIMBV to be the most reliable. This should be considered in the context of sensitivity to drug effect, and clinical meaningfulness of changes observed: all 5 motor outcomes were sensitive to drug effect of vamorolone and prednisone, whereas myometry was not."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Clinical studies of vamorolone: An anti-inflammatory corticosteroid with unique structure/activity relationships: not metabolized by HSD11B's, and a MR antagonist (ASBMR 2025) - No abstract available

Clinical • Orthopedics

Duchenne muscular dystrophy: Evolving therapeutic strategies and multidimensional evaluation approaches. (PubMed, Brain Dev) - "In this study, a comprehensive review of the current literature was conducted focusing on mutation-specific therapies (exon skipping and gene therapy), non-mutation-specific pharmacological interventions (steroids, vamorolone, and histone deacetylase inhibitors), and emerging modalities such as cell-based therapy...Vamorolones and givinostat are alternative drugs with improved safety profiles...Multidimensional stage-specific evaluations are essential to capture functional changes and their therapeutic effects. Ongoing research on gene-, pharmacological-, and cell-based therapies, coupled with robust outcome assessments, may further improve patient care and QOL."

Journal • Review • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Design and development of glucocorticoid receptor modulators. (PubMed, Trends Pharmacol Sci) - "A novel GRM, the dissociated steroid vamorolone, received marketing approval in 2024, confirming that altering the transrepression-transactivation profile is a valid strategy. Here, we review GR-mediated gene regulation and the transrepression-transactivation profile of GCs in relation to their anti-inflammatory efficacy and AEs. We highlight technological advances driving the design/development of novel GRMs, such as selective GR agonists and modulators (SEGRAMs), and provide insights into their mechanism of action."

Journal • Review

Vamorolone Versus Traditional Glucocorticoids in Duchenne Muscular Dystrophy: A Review and Meta-Analysis of Efficacy and Safety. (PubMed, J Pharm Technol) - "Search terms included (Vamorolone) AND (Corticosteroids OR Glucocorticoids OR Prednisone) AND (Duchenne Muscular Dystrophy OR related terms). Safety outcomes showed enhanced height percentile (MD = 16.28, 95% CI = 6.31-26.25, P = .001) and bone biomarkers (osteocalcin: MD = 15.68, P < .00001; P1NP: MD = 158.34, P < .00001), with no significant body mass index-z score difference. Vamorolone offers comparable efficacy with traditional glucocorticoids in DMD, with improved motor function and safer profiles in growth and bone health, suggesting its potential to transform DMD management."

Journal • Retrospective data • Review • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Pharmacological Insights on USFDA-Approved Novel Drug Therapies in the Year 2023. (PubMed, Curr Drug Discov Technol) - "The novel drug therapies approved by the USFDA hold significant potential to enhance the patient's care by providing advanced treatment modalities. This manuscript, reporting the comprehensive description of therapeutic aspects of the mentioned new drug therapies, underscores the commitment of the pharmaceutical sector to address the unmet medical needs and reshape the landscape of the healthcare service system by instilling optimism among patients and healthcare providers."

FDA event • Journal • Pediatrics • Rare Diseases

A phase II open-label, multiple dose study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of vamorolone in boys ages 2 to <4 years and 7 to <18 years with Duchenne Muscular Dystrophy (DMD) (clinicaltrialsregister.eu) - P2 | N=54 | Sponsor: Santhera Pharmaceuticals (Schweiz) AG

New P2 trial • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

The Long-Term Effects of Duchenne Muscular Dystrophy and its Treatment on Bone Strength (ESPE-ESE 2025) - "In an effort to attenuate the adverse effects of CS therapy in DMD, regimens alternative to daily CS have been implemented (such as prednisone 10 days on/off); however, this saltatory approach comes at a cost to muscle strength. Recently, a novel steroid (vamorolone) has been studied in DMD...In an effort to improve the convenience of osteoporosis treatment and minimize first exposure adverse events, denosumab has been tried in this setting...Overall, it is recognized that DMD is the ideal setting to consider not only prevention of first-ever fractures but also osteoanabolic agents, given the limitations of bisphosphonate monotherapy in low bone turnover states such as DMD. Strategic planning for primary osteoporosis prevention is currently underway by members of The OPTIMIZE DMD Consortium, an international working group dedicated to education, advocacy and research in endocrine and bone health care for people with DMD."

Acute Respiratory Distress Syndrome • Duchenne Muscular Dystrophy • Endocrine Disorders • Gene Therapies • Genetic Disorders • Muscular Dystrophy • Musculoskeletal Diseases • Nephrology • Orthopedics • Osteoporosis • Pediatrics • Renal Disease • Respiratory Diseases • Rheumatology

New perspectives - Glucocorticoids/vamorolone (ESPE-ESE 2025) - No abstract available

Duchenne Muscular Dystrophy

Santhera shares updates on commercial rollout of AGAMREE (GlobeNewswire) - "Santhera Pharmaceuticals...announces the latest progress on the commercial rollout of AGAMREE for the treatment of Duchenne Muscular Dystrophy (DMD)....Funding from National Health Service (NHS) England is now available for AGAMREE for the treatment of DMD, enabling prescribing in England to commence."

Reimbursement • Duchenne Muscular Dystrophy

Catalyst Pharmaceuticals Announces Health Canada’s Acceptance of AGAMREE New Drug Submission with Priority Review for Sub-Licensee Kye Pharmaceuticals (GlobeNewswire) - "Catalyst Pharmaceuticals...reported that its sub-licensee in Canada, Kye Pharmaceuticals, Inc. (Kye), has announced that Health Canada has accepted the New Drug Submission (NDS) for AGAMREE, a novel corticosteroid treatment for Duchenne muscular dystrophy (DMD), for review. The submission has been granted Priority Review, expediting the regulatory process with the potential for marketing authorization before the end of 2025. If approved, AGAMREE would be the first and only treatment option indicated for patients diagnosed with DMD in Canada."

Canada approval • Canada filing • Priority review • Duchenne Muscular Dystrophy

Vamorolone: a novel metabolism resistant steroid that suppresses joint destruction in chronic polyarthritis with reduced systemic side effects. (PubMed, Rheumatology (Oxford)) - "The findings suggest that at the effective anti-inflammatory dose examined in this study, vamorolone possesses a reduced profile of deleterious systemic effects relative to prednisolone. Whilst highlighting its potential for broader clinical application in inflammatory conditions, it remains unclear whether these side effects would remain mild at markedly higher doses."

Adverse events • Journal • Immunology • Inflammatory Arthritis • Oncology • Osteoporosis • Rheumatoid Arthritis • Rheumatology • IL6

Full Year Trading Update (GlobeNewswire) - "CHF 39.1 million (2023 CHF103.4 million), driven by strong underlying revenue growth offset by significant licensing milestones recognised in 2023 from out-licensing activities in major territories; CHF 14.8 million (2023 CHF 0.8 million) driven by the successful launch of AGAMREE in Germany and Austria...launches expected to follow in Italy, Spain, Nordics, Benelux, Portugal, Ireland, France and Switzerland through 2025 and the first half 2026. UK reimbursement has been secured, with initial sales already achieved in Scotland and the rest of the UK expected to follow by early Q2 2025; The Company...looks forward to long-term data readout from the GUARDIAN study, expected in Q4-25."

Launch Europe • Reimbursement • Duchenne Muscular Dystrophy

Association of DMD Gene Variant Classes With Motor Outcomes in a Drug Registration Clinical Trial Setting. (PubMed, Neurol Genet) - "We evaluated associations with baseline motor outcomes and treatment response (prednisone and vamorolone). This suggests that they may fail inclusion criteria (failure to follow commands; poor motor function). Subgroup analyses in DMD clinical trials at a young age range based on gene variant class may not reveal significant differences and would be relatively noninformative."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Early Cardiac Dysfunction in Duchenne Muscular Dystrophy: A Case Report and Literature Update. (PubMed, Int J Mol Sci) - "This case report presents a rare instance of early-onset cardiac involvement in a 3-year-old male with a confirmed deletion in exon 55 of the dystrophin gene...Genetic mechanisms and genotype-phenotype correlations related to cardiac involvement were reviewed, highlighting emerging therapies such as exon skipping, vamorolone, ifetroban, and rimeporide...While current DMD care standards improve survival, optimizing management through early intervention and novel therapies remains essential. Further research is needed to better understand genotype-phenotype correlations and improve cardiac outcomes for patients with DMD."

Journal • Review • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Genetic Disorders • Heart Failure • Muscular Dystrophy

A Parent Project Muscular Dystrophy-sponsored International Workshop Report on Endocrine and Bone Issues in Patients with Duchenne Muscular Dystrophy: An Ever-changing Landscape. (PubMed, J Neuromuscul Dis) - "Emerging knowledge about vamorolone (a novel dissociative steroid) and its effects on muscle, bone and endocrine health, and 9. Experiences implementing an endocrine-bone health management strategy nation-wide (in the UK). At the conclusion of the meeting, it was agreed that an endocrine-bone working group should be struck to continue the narrative, following which the International OPTIMIZE DMD Consortium was ignited to move the dial in these important areas."

Journal • Duchenne Muscular Dystrophy • Endocrine Disorders • Genetic Disorders • Muscular Dystrophy • Musculoskeletal Diseases • Nephrology • Orthopedics • Osteoporosis • Renal Disease • Rheumatology

The latest developments in synthetic approaches to duchenne muscular dystrophy. (PubMed, Expert Rev Neurother) - "Although corticosteroids remain the standard treatment, newly approved drugs such as exon-skipping therapies, vamorolone, delandistrogene moxeparvovec, and givinostat provide new treatment options...The accelerated FDA review process has enabled faster approval of new medications; however many have provided minimal clinical benefit to patients. Despite these challenges, continued drug development and innovative research offer hope to patients."

Journal • Review • Cardiomyopathy • Cardiovascular • Duchenne Muscular Dystrophy • Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Muscular Dystrophy • Respiratory Diseases

A Study to Assess Vamorolone in Becker Muscular Dystrophy (BMD) (clinicaltrials.gov) - P2 | N=39 | Active, not recruiting | Sponsor: ReveraGen BioPharma, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Muscular Dystrophy

Meta-analysis of the efficacy and safety of vamorolone in Duchenne muscular dystrophy. (PubMed, Neurol Sci) - "The results of our systematic review and meta-analyis are suggestive of improved efficacy and safety of vamorolone for DMD compared to standard glucocorticosteroids but the external validity of these findings as well as the medication's long-term effects remain to be determined."

Journal • Retrospective data • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

GUARDIAN: A Study on Safety and Effectiveness of Long-term Treatment With Vamorolone in Boys With Duchenne Muscular Dystrophy (clinicaltrials.gov) - P4 | N=80 | Recruiting | Sponsor: Santhera Pharmaceuticals

New P4 trial • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Evaluation of Vamorolone CYP3A4 Induction on Midazolam (a Sensitive CYP 3A4 Substrate) Pharmacokinetics (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Santhera Pharmaceuticals

New P1 trial

Metabolic Characterization of Vamorolone in Human Liver Microsomes: Implications for Anti-Doping. (PubMed, Drug Test Anal) - "The findings not only enhance the understanding of its metabolic mechanisms but also offer a scientific basis for evaluating its safety and efficacy in sports medicine. Meanwhile, these discoveries can contribute to better regulation and control of Vamorolone's use in competitive sports, ensuring fairness in competitions."

Journal