Recordati Rare Diseases announces the publication of the long-term outcomes from the open-label extension period of the Phase III LINC 3 study of ISTURISA in The European Journal of Endocrinology. These data support the long-term utility of ISTURISA in the maintenance treatment of patients with Cushing's disease and reinforce ISTURISA as an effective and well-tolerated oral therapy. ISTURISA is indicated in the United States for the treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative. Cushing's disease is a rare and debilitating condition of hypercortisolism that is caused by a pituitary adenoma.
The Phase III LINC 3 study was the largest prospective trial of an adrenal steroidogenesis inhibitor to date. In total, 106 of the 113 patients who completed the 48-week core phase opted to continue receiving open-label ISTURISA during the extension phase, which ended after all patients completed ≥72 weeks of treatment or had discontinued the study. Median duration of exposure to ISTURISA from core study baseline to end of the extension was 130 weeks (range 1–245).
Key findings published in the manuscript entitled 'Long-term outcomes of osilodrostat in Cushing's disease: LINC 3 study extension' include:
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The normalization in mean urinary free cortisol (mUFC) achieved during the core phase was maintained, with mean mUFC ≤ upper limit of normal (ULN) throughout the extension; at
week 72, 86/106 (81.1%) patients had mUFC ≤ULN
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The median average ISTURISA dose from core study start to end of the extension was
7.4 mg/day (range 0.8–46.6); dose received stabilized during the extension, indicating that ISTURISA treatment provided a sustained response without need for up-titration over time.
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Observed improvements in most cardiovascular and metabolic-related parameters associated with Cushing's disease at the end of the core study were maintained or further improved with long-term treatment.
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Patient-reported quality of life (QoL) scores (CushingQoL and Beck Depression Inventory) also continued to improve during long-term treatment.
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Improvements in physician-rated severity scores for physical manifestations of hypercortisolism were evident within 12 weeks of ISTURISA treatment; the proportion of patients rated with an improvement was maintained or increased with longer follow-up, including improvement in hirsutism in female patients.
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In female patients, estradiol and testosterone levels tended to return to baseline levels with longer follow-up.
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ISTURISA was well tolerated in most patients, with no unexpected adverse events (AEs) compared with that observed in the core phase; AEs of special interest including hypocortisolism-related and adrenal hormone precursor-related AEs were generally less frequently reported during the extension phase than the core.
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The most common AEs regardless of study drug relationship were nausea (45.3%), headache, (36.5%) and fatigue (32.8%).