The European medicines regulator has issued a positive opinion expanding the approved uses for hydrocortisone (Efmody, Neurocrine Netherlands) to include the treatment of adrenal insufficiency in adults and adolescents aged 12 years and older. The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended updating the marketing authorization to cover this broader patient population.

Adrenal insufficiency is a potentially life‑threatening endocrine disorder defined by inadequate cortisol production, whether from primary adrenal failure (eg, Addison disease) or secondary causes (pituitary/adrenal axis dysfunction). Lifelong cortisol replacement is essential to prevent adrenal crises and manage symptoms such as fatigue, weight loss, hypotension, and electrolyte imbalances.

Efmody is a modified‑release hydrocortisone formulation (oral capsules) designed to mimic the physiological diurnal rhythm of cortisol secretion using controlled‑release hard capsules. Unlike immediate‑release hydrocortisone tablets, which require multiple daily dosing and produce peaks and troughs, the modified‑release design aims to deliver hydrocortisone in a smoother profile, potentially aligning better with endogenous cortisol patterns.

Efmody received its initial marketing authorization in Europe in May 2021 for the treatment of congenital adrenal hyperplasia in adults and adolescents aged 12 years or older.

Clinical Rationale 

Although the pivotal clinical trials of Efmody were conducted in patients with congenital adrenal hyperplasia, the underlying principle of cortisol replacement is also shared with primary and secondary adrenal insufficiency. 

Efmody’s previous EMA approval was based on a pivotal 24-week study of 122 patients with congenital adrenal hyperplasia, where Efmody was compared with standard corticosteroid therapy. The primary endpoint — a composite score based on 17-hydroxyprogesterone (17-OHP) levels — fell by 0.403 with Efmody vs 0.172 with standard treatment. While the difference did not demonstrate clear superiority, Efmody showed better control of morning 17-OHP levels, supporting a more physiological cortisol profile. Robust comparative outcome data in adrenal insufficiency populations are still needed.

Several lines of clinical and pharmacological evidence support the use of Efmody as a physiologically relevant cortisol replacement strategy. Besides its ability to approximate the endogenous 24-hour circadian cortisol rhythm, Efmody is currently the only oral glucocorticoid formulation capable of reproducing the late-night and early-morning rise in cortisol, a phase that is absent in standard therapy and is thought to contribute to early-morning fatigue and impaired well-being in patients with primary adrenal insufficiency.

While the formulation does not replicate ultradian cortisol pulsatility, it offers the most complete circadian coverage currently achievable with an oral therapy, without the technical complexity and burden of subcutaneous hydrocortisone pump infusion.

Marketing Authorization Details 

Neurocrine Netherlands holds the marketing authorization for this medicinal product. The CHMP opinion represents a modification to the existing authorization rather than a new approval, expanding the eligible patient population.

Detailed recommendations will be included in the updated Summary of Product Characteristics, to be published on the EMA website in all official European Union languages following the European Commission’s decision on the marketing authorization change.