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

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

Evaluation of Vamorolone Mineralocorticoid Receptor Antagonism in Healthy Subjects (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Santhera Pharmaceuticals

New P1 trial

A Study to Assess Vamorolone in Boys Ages 2 to <4 Years and 7 to <18 Years With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P2 | N=54 | Completed | Sponsor: Santhera Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Corticosteroids, Vamorolone and Other Oral Treatments (ICNMD 2024) - "The randomized, blinded, placebo and prednisone-controlled Phase 3 study of vamorolone in DMD demonstrated similar muscle functional benefits to prednisone with some lessening of side effects. Future clinical studies and experience will shed light on a role for vamorolone in combination with other treatments developed for the medical management of patients with DMD and BMD. Key words: Duchenne muscular dystrophy, Becker muscular dystrophy, vamorolone, corticosteroids"

Becker Muscular Dystrophy • Cataract • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Ophthalmology

Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A Systematic Review. (PubMed, Paediatr Drugs) - "According to our results, vamorolone offers a statistically and clinically significant benefit in the management of Duchenne muscular dystrophy, with fewer side effects than glucocorticoids. However, the number of studies limits the interpretability and generalisability of these data, requiring more studies with more participants to perform a meta-analysis."

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

Efficacy and safety of different doses of vamorolone in boys with Duchenne muscular dystrophy: a systematic review and network meta-analysis. (PubMed, Front Neurol) - "We conducted a study to evaluate the efficacy of different doses of vamorolone in boys with DMD, and compare the safety of vamorolone vs. glucocorticosteroids, prednisone or deflazacort in boys with DMD. However, more large sample randomized controlled trials are needed to confirm our results. This systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration number: CRD42024562916)."

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

Registry Study to Observe Long-term Safety of Vamorolone (AGAMREE®) in Patients With Duchenne Muscular Dystrophy. (clinicaltrials.gov) - P=N/A | N=250 | Recruiting | Sponsor: Catalyst Pharmaceuticals, Inc.

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

A Study to Assess Vamorolone in Becker Muscular Dystrophy (BMD) (clinicaltrials.gov) - P2 | N=39 | Recruiting | Sponsor: ReveraGen BioPharma, Inc. | Trial completion date: Jan 2025 ➔ Jun 2025 | Trial primary completion date: Jan 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Muscular Dystrophy

Corticosteroids for the treatment of duchenne muscular dystrophy: a safety review. (PubMed, Expert Opin Drug Saf) - "When selecting a medication for a patient, the decision-making process will most likely rely on the minor differences in the adverse effect profiles. Whichever medication is utilized will surely be a part of a larger regimen that includes other novel therapeutic agents."

Adverse events • Journal • Review • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Adrenal suppression from vamorolone and prednisone in Duchenne muscular dystrophy: results from the phase 2b clinical trial. (PubMed, J Clin Endocrinol Metab) - "AS after vamorolone and prednisone was frequent and vamorolone-associated AS appeared dose-dependent. A lower stimulated cortisol threshold may be appropriate when using a monoclonal assay. We recommend hydrocortisone for glucocorticoid stress dosing in patients receiving vamorolone."

Clinical • Journal • P2b data • Duchenne Muscular Dystrophy • Endocrine Disorders • Genetic Disorders • Muscular Dystrophy • Nephrology • Pediatrics • Renal Disease

Bioengineered Model of Human LGMD2B Skeletal Muscle Reveals Roles of Intracellular Calcium Overload in Contractile and Metabolic Dysfunction in Dysferlinopathy. (PubMed, Adv Sci (Weinh)) - "Treatment with the ryanodine receptor (RyR) inhibitor dantrolene or the dissociative glucocorticoid vamorolone restores LGMD2B contractility, improves membrane repair, and reduces LD accumulation. Lastly, it is demonstrated that chemically induced chronic RyR leak in healthy myobundles phenocopies LGMD2B contractile and metabolic deficit, but not the loss of membrane repair capacity. Together, these results implicate intramyocellular Ca2+ leak as a critical driver of dysferlinopathic phenotype and validate the myobundle system as a platform to study LGMD2B pathogenesis."

Journal • Metabolic Disorders • Muscular Dystrophy