Efmody (hydrocortisone modified release) / Abiogen, Neurocrine - LARVOL DELTA

The Current Treatment Landscape for Congenital Adrenal Hyperplasia. (PubMed, Drugs) - "Modified-release hydrocortisone formulations, such as Efmody® and Plenadren®, as well as continuous subcutaneous infusion therapies, have been developed to help better mimic physiological cortisol rhythms...This review provides an overview of current standard-of-care treatments for CAH and highlights recent advancements in therapeutic strategies. By addressing the limitations of traditional glucocorticoid replacement, these innovations have the potential to improve long-term outcomes and quality of life for patients with CAH."

Journal • Review • Congenital Adrenal Hyperplasia • Endocrine Disorders • CYP1A2 • CYP21A2

A Double-blind Study of Modified-release Hydrocortisones, Chronocort versus Plenadren, in Adrenal Insufficiency (CHAMPAIN) (ENDO 2025) - "In adrenal insufficiency Chronocort provides physiological waking cortisol levels and is associated with reduced fatigue and improved QoL as compared to Plenadren."

Clinical • Endocrine Disorders • Fatigue • Nephrology • Renal Disease

Long-term outcomes in patients with congenital adrenal hyperplasia treated with hydrocortisone modified-release hard capsules. (PubMed, Eur J Endocrinol) - "MRHC treatment resulted in hydrocortisone dose reduction followed by a stable dose with improved biochemical control associated with fertility. Biochemical control could be reliably monitored by a single blood sample taken between 09:00h and 13:00h. The incidence of adrenal crises was below that reported previously in patients with CAH."

Journal • Congenital Adrenal Hyperplasia • Endocrine Disorders • Nephrology • Renal Disease

Switching Patients With Congenital Adrenal Hyperplasia to Modified-Release Hydrocortisone Capsules: Relative Bioavailability and Disease Control. (PubMed, Clin Endocrinol (Oxf)) - "MRHC showed comparable bioavailability to IRHC based on cortisol AUC after 20 mg administration. Switching patients treated with IRHC to a twice daily MRHC regimen on the same daily dose (giving approximately two thirds of the dose at night) is an effective protocol for starting MRHC treatment."

Journal • Congenital Adrenal Hyperplasia • Endocrine Disorders • Nephrology • Renal Disease

Achieving Spontaneous Pregnancy in a Patient with Classic Congenital Adrenal Hyperplasia through Modified-Release Hydrocortisone (ESPE-ESE 2025) - "To optimise disease control her treatment was adjusted multiple times, including the use of prednisolone and dexamethasone, dose escalations and additional fludrocortisone. The presented case of a female patient with classic CAH and infertility for over three years highlights the challenges of fertility treatment in CAH. The normalisation of morning follicular progesterone concentrations and the successful spontaneous pregnancy under MR-HC treatment, indicate that due to the circadian release MR-HC normalises adrenal steroid precursor synthesis in a more physiologic manner. Therefore, it could be a promising therapeutic option for fertility treatment in women with classic CAH."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Gynecology • Infertility • Sexual Disorders

A Double-blind Study of Modified-release Hydrocortisones, Chronocort versus Plenadren, in Adrenal Insufficiency (CHAMPAIN) (ESPE-ESE 2025) - "In adrenal insufficiency** Chronocort provides physiological waking cortisol levels and is associated with reduced fatigue and improved QoL as compared to Plenadren."

Clinical • Endocrine Disorders • Fatigue • Nephrology • Renal Disease

Treatment of children and adolescents with congenital adrenal hyperplasia with hydrocortisone modified-release hard capsules (ESPE-ESE 2025) - "Context: The standard treatment for congenital adrenal hyperplasia (CAH) in childhood includes hydrocortisone and, for salt-wasting CAH, fludrocortisone supplementation...Conventional fast- acting hydrocortisone often fails to adequately suppress the early morning surge of 17-OH progesterone (17OHP), and the requirement for three daily doses poses adherence challenges... HMRC treatment in children with CAH improves morning pre-dose 17OHP levels, while growth rates align more closely with the parental target height. No significant adverse effects or severe complications were observed. Further research is needed to assess long-term outcomes and quality of life."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders

17OHP and cortisol day curve profiles for children using hard-capsule modified release hydrocortisone as compared with immediate release hydrocortisone (ESPE 2024) - "Patient characteristics are shown in Table 1. Subject 8 (with SAI) stopped MRH due to a lack of symptomatic improvement after 1 month so had no cortisol profiles. Subject 9 (with SAI) had no cortisol day curves obtained before transitioning to adult services."

Clinical • Congenital Adrenal Hyperplasia • Endocrine Disorders • Nephrology • Pediatrics • Rare Diseases • Renal Disease

Effects of the modified release hydrocortisone preparation Efmody® on hormones, spermatogenesis and body weight in males with congenital adrenal hyperplasia (ESPE 2024) - "The median Efmody® dose required for optimal cortisol replacement was 16 mg/m2 (10-22.7), corresponding to 30 mg/day (25-50), with one third of the daily dose taken at 7:00 a.m. and two thirds taken at 11.00 p.m. The dose of fludrocortisone was not changed. The modified release hydrocortisone preparation Efmody® seems to be a valid alternative to conventional glucocorticoid replacement in men with CAH, with potential beneficial effects on hypothalamic-pituitary-adrenal and -gonadal axis hormone concentrations, semen quality and body weight."

Congenital Adrenal Hyperplasia • Endocrine Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Orthopedics • Pain • CYP1A2

3D printed, personalized hydrocortisone for hypocortisolemia. (ESPE 2024) - "3D printed SR and DR hydrocortisone tablets were developed for patients with AI. The quality of 3D tablets is higher than pharmacy compounded capsules, while manufacturing costs are feasible. The 3D therapy is once-daily, compared to three times a day of the SOC, reducing pill-frequency."

Endocrine Disorders • Nephrology • Pediatrics • Renal Disease

Long-term Safety Study of Chronocort in the Treatment of Participants with Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P3 | N=76 | Enrolling by invitation | Sponsor: Diurnal Limited | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Congenital Adrenal Hyperplasia • Endocrine Disorders

Comparison of modified-release hydrocortisone capsules versus prednisolone in the treatment of congenital adrenal hyperplasia. (PubMed, Endocr Connect) - "MRHC reduces 17OHP at 09:00h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients."

Journal • Congenital Adrenal Hyperplasia • Endocrine Disorders

CHAMPAIN Study: Initial Results From A Phase II Study Of Efficacy, Safety And Tolerability Of Modified-release Hydrocortisones: Chronocort® (Efmody®) Versus Plenadren®, In Primary Adrenal Insufficiency (ENDO 2024) - "Abstract is embargoed at this time."

Clinical • Late-breaking abstract • P2 data • Endocrine Disorders • Nephrology • Renal Disease

CHAMPAIN Study: Initial Results From A Phase II Study Of Efficacy, Safety And Tolerability Of Modified-release Hydrocortisones: Chronocort® (Efmody®) Versus Plenadren®, In Primary Adrenal Insufficiency (ENDO 2024) - "Chronocort® provides more physiological waking cortisol levels than Plenadren®. Further analysis will test the hypothesis that waking with physiological cortisol levels improves fatigue and QoL in patients with PAI. 1.Mah PM, et al."

Clinical • Late-breaking abstract • P2 data • Congenital Adrenal Hyperplasia • Endocrine Disorders • Fatigue • Nephrology • Rare Diseases • Renal Disease

Incidence of Adrenal Crisis in Congenital Adrenal Hyperplasia (CAH) Patients During a Prospective Monitored Long-Term Study of Modified-Release Hydrocortisone (MRHC) Capsules, (Efmody) (ENDO 2024) - "Data from this longest prospectively monitored study in CAH suggest that the incidence of adrenal crisis on MRHC is at the low end of that reported in retrospective studies and the safety profile of MRHC is otherwise similar to immediate release hydrocortisone. Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins."

Clinical • Cardiovascular • Congenital Adrenal Hyperplasia • Endocrine Disorders • Fatigue • Musculoskeletal Pain • Myocardial Infarction • Nephrology • Renal Disease

Morning Cortisol Levels in Patients With Established Primary Adrenal Insufficiency (ENDO 2024) - "We have developed a modified-release formulation of hydrocortisone to replace the physiological cortisol circadian rhythm and are undertaking a Double-Blind, Double-Dummy, Two-Way Cross-Over, Randomised, Phase II Study of Modified-Release Hydrocortisones: Chronocort® Versus Plenadren® in PAI... In patients with an established diagnosis of PAI, the majority had undetectable morning cortisol, but cortisol was detectable in 41% of patients and above 140 nmol/L in 13% confirming previous publications 2. Retesting patients with a cortisol >50nmol/L showed very similar results suggesting that the detectable cortisol was not an artefact and likely due to background cortisol secretion. 1."

Clinical • Endocrine Disorders • Immunology • Nephrology • Renal Disease

CHAMPAIN: Chronocort Versus Plenadren Replacement Therapy in Adults With Adrenal Insufficiency (clinicaltrials.gov) - P2 | N=58 | Completed | Sponsor: Diurnal Limited | Active, not recruiting ➔ Completed

Trial completion • Endocrine Disorders • Nephrology • Renal Disease

Long-term Safety Study of Chronocort in the Treatment of Participants With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P3 | N=81 | Enrolling by invitation | Sponsor: Diurnal Limited | N=181 ➔ 81 | Trial completion date: Apr 2026 ➔ Dec 2024 | Trial primary completion date: Apr 2026 ➔ Dec 2024

Enrollment change • Trial completion date • Trial primary completion date • Congenital Adrenal Hyperplasia • Endocrine Disorders

CONnECT: Comparison of Chronocort Versus Standard Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P3 | N=55 | Completed | Sponsor: Diurnal Limited | Active, not recruiting ➔ Completed

Trial completion • Congenital Adrenal Hyperplasia • Endocrine Disorders • BGLAP

Novel agents to treat adrenal insufficiency: findings of preclinical and early clinical trials. (PubMed, Expert Opin Investig Drugs) - "CHSI has significant potential for individualized glucocorticoid dosing, however would require a suitable biomarker of glucocorticoid adequacy to be implementable. Avenues of future research include determine a glucocorticoid sufficiency biomarker, development of interstitial or systemic cortisol monitoring or development of glucocorticoid receptor modulators."

Journal • Preclinical • Review • Endocrine Disorders • Nephrology • Renal Disease

Long-term Safety Study of Chronocort in the Treatment of Participants With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P3 | N=181 | Enrolling by invitation | Sponsor: Diurnal Limited | Trial completion date: Jan 2025 ➔ Apr 2026 | Trial primary completion date: Jan 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Congenital Adrenal Hyperplasia • Endocrine Disorders

CONnECT: Comparison of Chronocort Versus Standard Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia (clinicaltrials.gov) - P3 | N=53 | Active, not recruiting | Sponsor: Diurnal Limited | N=150 ➔ 53 | Trial completion date: Aug 2024 ➔ Feb 2024 | Trial primary completion date: Jul 2024 ➔ Feb 2024

Enrollment change • Trial completion date • Trial primary completion date • Congenital Adrenal Hyperplasia • Endocrine Disorders • BGLAP