Calcort (deflazacort) / Sanofi - LARVOL DELTA

[VIRTUAL] Development of a novel weight-based steroid emergency plan for patients with Duchenne Muscular Dystrophy (ESPE 2021) - "We are currently reviewing the results of our practice change. Anecdotally families report faster recovery times from illness since using stress-doses of hydrocortisone alongside their usual glucocorticoid. Previous regimens utilising a patients usual disease-modifying glucocorticoid may not have taken into account the pharmacokinetics of these drugs; Deflazacort for example has a rapid plasma elimination half-life of 1-2 hours."

Clinical • Duchenne Muscular Dystrophy • Endocrine Disorders • Genetic Disorders • Muscular Dystrophy • Nephrology • Renal Disease

[VIRTUAL] Use of lateral DEXA scanning for identifying and monitoring vertebral fractures in patients affected by Duchenne Muscular Dystrophy. (ESPE 2021) - "62.2% ( n = 23) were taking deflazacort, 32.4% ( n = 12) taking prednisolone and in 5.4% ( n = 2) steroids had been discontinued...Of all 37 who underwent VFA, 35.1% ( n = 13) had a change in management following the image findings; five started zoledronic acid, three recommenced zoledronic acid and five were referred for testosterone initiation. Our findings parallel that of prior studies and support the use of VFA as a screening tool for identifying VF in boys affected by DMD. This adds weight to the current evidence base that forms the recommendations for routine spinal imaging in DMD and promotes proactive bone health surveillance."

Clinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Musculoskeletal Diseases • Orthopedics • Pain • Pediatrics

[VIRTUAL] Evaluation of Asthma control and oral corticosteroids in Severe Asthma (ERS 2021) - "As add-on to inhalation therapy, 383 patients took OCS: Dexamethasone 0.7%, Deflazacort 1.6%, Betamethasone 2.7%, Methylprednisolone 8.5%, Prednisone 17.6%. Despite high-dose inhalation therapy plus additional controllers or OCS, only 34% of patients affected by SA had controlled asthma. Moreover, 31% of subjects daily took OCS. Of note, uncontrolled patients had a high eosinophilia and few were properly treated with biologics."

Allergy • Asthma • Eosinophilia • Immunology • Pulmonary Disease • Respiratory Diseases

Influence of Different Types of Corticosteroids on Heart Rate Variability of Individuals with Duchenne Muscular Dystrophy-A Pilot Cross Sectional Study. (PubMed, Life (Basel)) - " Corticosteroids have the potential to affect the cardiac autonomic modulation in adolescents with DMD. The use of Prednisone/Prednisolone appears to promote improved responses in terms of sympathovagal activity as opposed to Deflazacort."

Clinical • Journal • Observational data • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Evaluating longitudinal therapy effects via the North Star Ambulatory Assessment. (PubMed, Muscle Nerve) - P3 | "Unlike fixed-time analyses, this analytical approach enabled demonstration of cumulative, longitudinal treatment effects over time using repeatedly measured NSAA observations."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

A Systematic Review and Meta-analysis of Adjuncts to Minimally Invasive Treatment of Urethral Stricture in Men. (PubMed, Eur Urol) - "Adjuncts to minimally invasive treatment of USD appear to lower the recurrence rate and are associated with a low adjunct-specific complication rate. However, the studies included were at high risk of bias. Mitomycin C is the adjunct supported by the highest level of evidence."

Journal • Retrospective data • Review • Gastrointestinal Disorder • Infectious Disease • Nephrology • Pruritus • Urology

Steroid switching in dystrophinopathy treatment: a US chart review of patient characteristics and clinical outcomes. (PubMed, J Comp Eff Res) - "Aim: To describe reasons for switching from prednisone/prednisolone to deflazacort and associated clinical outcomes among patients with Duchenne and Becker muscular dystrophy (DMD and BMD, respectively) in the USA...Switching was 'very' or 'somewhat' effective at addressing the primary reasons in 90-95% of patients. Physician-reported outcomes were consistent with deflazacort addressing patients' primary reasons for switching."

Clinical • Clinical data • Journal • Review • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Standardization of skin tests with systemic corticosteroids for immediate hypersensitivity reactions (EAACI 2021) - "SixsCS[betamethasone 0.5 mg/mL (Bm), deflazacort 22.75 mg/mL (Dz), dexamethasone 4 mg/mL (Dx), hydrocortisone 50 mg/mL (Hc), methylprednisolone 62.5 mg/mL (Mp) and prednisolone125 mg/mL(Pd)] and 2 excipients (carboxymethycellulose as Celluvisc1% and polyethylene glycol as Movicol) were tested. Our work suggests for the 1sttime, the NIC for sCS. Drug challenges in more patients are underway to fully validate the proposed NIC."

Immunology

Cymbopogon winterianus Essential Oil Attenuates Bleomycin-Induced Pulmonary Fibrosis in a Murine Model. (PubMed, Pharmaceutics) - "The treatment was performed using daily oral administration of distilled water, EOCW at 50, 100, and 200 mg/kg, and deflazacort (DFC). EOCW significantly reduced inflammation in BALF, reduced MDA levels, and increased SOD activity. EOCW attenuated histological grading of PF and reduced immunohistochemical expression of α-SMA and TGF-β in a dose-dependent way, likely due to the reduction of oxidative stress, inflammation, and TGF-β-induced myofibroblast differentiation."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CAT • TGFB1

[VIRTUAL] Noninvasive Ventilation Usage and Adherence in Children and Adults with Duchenne Muscular Dystrophy: A Multicenter Analysis (ATS 2021) - "Multivariate analysis is planned to evaluate the impact of FVC and Deflazacort on adherence. Future investigations will evaluate the specific impact of socioeconomic and clinical outcomes on NIV usage and adherence across the spectrum of disease."

Clinical • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Pediatrics • Respiratory Diseases

Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy. (PubMed, Orphanet J Rare Dis) - "Genotype variation influences clinical progression in certain DMD groups. Beneficial responses to GC treatment were observed among all DMD genotypes. Compared with other genotypes, deletions amenable to skipping exon 44 had a lower hazard ratio, which may indicate a stronger protective effect of GC treatments on this subgroup. These data are valuable for designing future clinical trials, as clinical outcomes may be influenced by the genotypes."

Clinical • Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

In vitro cytochrome P450- and transporter-mediated drug interaction potential of 6β-hydroxy-21-desacetyl deflazacort-A major human metabolite of deflazacort. (PubMed, Pharmacol Res Perspect) - "C-6β-OH-21-desDFZ was biosynthesized using bacterial biotransformation and the subsequent study showed that 6β-OH-21-desDFZ was not a substrate for human BCRP, MDR1, MATE1, MATE2-K, OAT1, OATP1B1, OATP1B3, and OCT2 transporters, but appeared to be an in vitro substrate for the human OAT3 uptake transporter. At plasma concentrations of 6β-OH-21-desDFZ seen in the clinic, CYP- and transporter-mediated drug-drug interactions are not expected following administration of a therapeutic dose of DFZ in Duchenne muscular dystrophy (DMD) patients."

Journal • Preclinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • ABCB1 • CYP1A2 • CYP2C19 • CYP3A4

DACORSIN/4: Study of the Excretion of Orally Administered Corticosteroids for the Improval of the Detection of Said Substances in Anti-doping Controls (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Parc de Salut Mar

New P1 trial

[VIRTUAL] Ataluren delays loss of ambulation and decline in pulmonary function in patients with nonsense mutation Duchenne muscular dystrophy (MDA 2021) - P=N/A, P3 | "Propensity score matching identified Study 019 and CINRG DNHS patients with comparable indicators of disease severity: age at first symptoms, corticosteroid type (deflazacort or other), and duration of use... Ataluren + SoC delays LoA and may delay pulmonary function decline in nmDMD patients compared with DMD patients receiving SoC, although longer follow-up will be required to more fully assess this latter outcome."

Clinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Palliative care

[VIRTUAL] 2.5-years of Vamorolone Treatment in Duchenne Muscular Dystrophy: Results of an Open Label Long-Term Extension (MDA 2021) - "Vamorolone is a first-in-class steroidal anti-inflammatory drug with novel structure/activity relationships with glucocorticoid and mineralocorticoid receptor targets compared to deflazacort or prednisone. Stratification of participants by baseline age (5 years) showed consistent results within both strata for many outcome measures, indicating a disease modifying effect. Vamorolone treatment was not associated with typical safety concerns of corticosteroid treatment (slowing of linear growth, insulin resistance, decreases in osteocalcin)."

Clinical • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

[VIRTUAL] REAL-WORLD REASONS FOR STEROID SWITCHING AND ASSOCIATED CLINICAL OUTCOMES AMONG PATIENTS WITH DYSTROPHINOPATHIES: NATIONWIDE REVIEW OF MEDICAL RECORDS (MDA 2021) - "BACKGROUND: Corticosteroid treatment with prednisone/prednisolone or deflazacort is the standard of care for dystrophinopathies... In this real-world study, the majority of switching from prednisone to deflazacort aimed to improve benefit-risk. During 6-months average follow-up after switching in this uncontrolled study, physicians reported lower proportions of most adverse effects compared to the pre-switch period. Among the minority of charts with disease severity recorded, most showed stability of progressive disease."

Clinical • Clinical data • Real-World Evidence • Review • Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Obesity

[VIRTUAL] Propensity score matching enables comparison of rare disease product registry data with an external study comparator (MDA 2021) - P=N/A | "PSM was used to identify CINRG DNHS patients who were comparable to STRIDE patients to enable assessment of treatment effect, in this case that of ataluren, in the STRIDE study...Propensity matching of the CINRG DNHS population yielded a comparable population (N=181) to the STRIDE effectiveness population (N=181) with respect to age at first symptoms (P=0.4766), age at first corticosteroid use (P=0.8607), duration of deflazacort use (P=0.3642) and duration of the use of other corticosteroids (P=0.8976). To assess treatment effect, PSM enabled comparison of rare disease product registry data with an external study in terms of age at loss of ambulation, an important disease milestone of DMD progression."

Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Rare Diseases

Cotrimoxazole prophylaxis prevents major infective episodes in patients with systemic lupus erythematosus on immunosuppressants: A non-concurrent cohort study. (PubMed, Lupus) - "Cotrimoxazole prophylaxis in SLE patients on immunosuppression prevents major infections."

Clinical • Journal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I) (clinicaltrials.gov) - P3; N=30; Completed; Sponsor: PTC Therapeutics; Active, not recruiting ➔ Completed

Clinical • Trial completion • Muscular Dystrophy

Heart Rate Variability in Individuals With Duchenne Muscular Dystrophy (clinicaltrials.gov) - P; N=40; Completed; Sponsor: University of Sao Paulo

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

Response Surface Optimization of Ultra-Elastic Nanovesicles Loaded with Deflazacort Tailored for Transdermal Delivery: Accentuated Bioavailability and Anti-Inflammatory Efficacy. (PubMed, Int J Nanomedicine) - "The current work divulged successful augmentation of the bioavailability of DFZ optimum formulation by about 1.37-fold and drug release retardation compared to oral drug tablets besides significant depression of edema, cellular inflammation and capillary congestion in carrageenan-induced rat paw edema model. The transdermal DFZ-UENVs can achieve boosted bioavailability and may be suggested as an auspicious non-invasive alternative platform for oral route."

Clinical • Journal • CNS Disorders • Depression • Gastrointestinal Disorder • Immunology • Inflammation • Psychiatry

Study of Edasalonexent With Midazolam and Deflazacort in Healthy Subjects (clinicaltrials.gov) - P1; N=26; Completed; Sponsor: Catabasis Pharmaceuticals; Active, not recruiting ➔ Completed

Clinical • Trial completion

Evaluation of the Effects of Pre-operative Deflazacort on Post-operative Pain, Edema and Trismus (clinicaltrials.gov) - P4; N=35; Active, not recruiting; Sponsor: Yuzuncu Yıl University; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Nov 2020 ➔ Nov 2021

Trial completion date • Trial primary completion date • Pain

The Effect of Deflazacort Treatment on the Functioning of Skeletal Muscle Mitochondria in Duchenne Muscular Dystrophy. (PubMed, Int J Mol Sci) - "In this case, deflazacort also affected the mitochondria of WT mice. The paper discusses the mechanisms underlying the effect of deflazacort on the functioning of mitochondria and contributing to the improvement of the muscular function of mdx mice."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Metabolic Disorders • Muscular Dystrophy

Efficacy of corticosteroid in decreasing scoliosis and extending time to loss of ambulation in a single clinic: an effectiveness trial. (PubMed, J Child Orthop) - "Of these 32 were steroid naïve, 37 took the recommended dose (standard of care, SOC) of Prednisone or Deflazacort, and 32 took a lower dose (LD). Many published studies have inadequate data on scoliosis probably due to the lack of inclusion of orthopaedists in the study group. IV."

Clinical • Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy