EFMODY Modified-release hard capsule Ref.[50004] Active ingredients:

Pharmacotherapeutic group: Corticosteroids for systemic use; glucocorticoids
ATC code: H02AB09

Mechanism of action

Hydrocortisone is a glucocorticoid. Glucocorticoids have multiple effects in multiple tissues through actions on the intracellular steroid receptors.

Pharmacodynamic effects

Hydrocortisone is a glucocorticoid and the synthetic form of endogenously produced cortisol. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastro-intestinal tract. Cortisol is the principal corticosteroid secreted by the adrenal cortex. Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have saltretaining properties, are used as replacement therapy in adrenocortical deficiency states. They are also used for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body’s immune responses to diverse stimuli.

Clinical efficacy and safety

A study in 122 participants with genetically diagnosed 21-hydroxylase deficiency randomised to Efmody or continuation of standard care with blinded titration of dose and regular overnight profiles failed to meet its primary endpoint of superiority in change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) profile for 17-hydroxyprogesterone 17-OHP. The 17-OHP SDS was lower in the Efmody cohort than standard therapy at 4 and 12 weeks. At 24 weeks the 17-OHP SDS was lower in the morning period (07:00 hrs to 15:00 hrs) but not in the evening or overnight (see also Figure 1 for the geometric mean 24-hour profile of 17-OHP after 24 weeks intensive treatment). A reduction in the 17-OHP area under the curve occurred in both groups, with greater reduction in the Efmody cohort. The percentage of patients with controlled 09:00 hrs 17-OHP (<36nmol/l) was 50% at baseline and at 24 weeks was 91% in the Efmody cohort and 71% in the standard therapy cohort. Efmody patients suffered no adrenal crises (compared to 3 in the control arm) and had fewer sick day episodes where increased dosing due to stress was required was required (26 vs 36 in the control arm) despite reporting more episodes of intercurrent infective or gastro-intestinal illness. Glucocorticoid daily dose, measured as a hydrocortisone equivalent dose, increased in most subjects during the study (see Table 2).

Table 2. Glucocorticoid daily dose changes during the phase 3 study DIUR-005:

Figure 1. End of study geometric mean 24-hour profile of 17-OHP after 24 weeks intensive treatment with either Efmody (closed circles) or standard therapy (open circles):

A safety extension study of 91 patients with titration by investigators was characterised by dose reductions with median daily dose of Efmody at 18 months interim analysis (n=50) being 20 mg (from a median baseline daily dose of 30 mg) with 17-OHP levels remaining in the clinically determined optimal range and androstenedione at or below the reference range for normal individual.

In the safety assessment of clinical studies, differences between the treatment arms in treatment related AE’s were reported (by preferred term [PT]). The most notable differences between the Efmody and standard glucocorticoid therapy pools, respectively, were observed for headache (7.5% vs 1.6%), increased appetite (5.8% vs 3.3%), weight increase (including abnormal weight gain) (9.2% vs1.6%), decreased appetite (5.0% vs 0%) and nausea (4.2% vs 1.6%).