08:00 uur 31-08-2022

Recordati Rare Diseases Announce Publication of Long-term Outcomes From the Extension to the Phase III LINC 3 Study of Isturisa® (Osilodrostat) in Patients With Cushing’s Disease in the European Journal of Endocrinology

Long-term findings from the multicentre, international LINC 3 study demonstrated that treatment with Isturisa® (osilodrostat) maintains cortisol normalisation and is well tolerated in most patients with Cushing’s disease.

PUTEAUX, France–(BUSINESS WIRE)– Recordati Rare Diseases announce today 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.1 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 EU for the treatment of adult patients with endogenous Cushing’s syndrome,2 a rare and debilitating condition of hypercortisolism that is caused by a pituitary adenoma (Cushing’s disease).3

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:1

  • The normalisation 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
  • The median average osilodrostat dose from core study start to end of the extension was

    7.4 mg/day (range 0.8–46.6); dose received stabilised during the extension, indicating that Isturisa treatment provides a sustained response without need for uptitration over time
  • 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
  • Patient-reported quality of life (QoL) scores (CushingQoL and Beck Depression Inventory) also continued to improve during long-term treatment
  • 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
  • In female patients, oestradiol and testosterone levels tended to return to baseline levels with longer follow-up
  • 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

“Findings from our large trial, where patients with Cushing’s disease opted to continue treatment with osilodrostat during the extension, support osilodrostat as an effective, long-term treatment option for patients with this chronic disease,” said Maria Fleseriu, Professor of Medicine (Endocrinology) and Neurological Surgery and Director of the Pituitary Center at Oregon Health & Science University, Portland, OR, USA. “Importantly, as well as providing long-term normalisation of cortisol, continued treatment with osilodrostat for over 72 weeks led to sustained improvements in clinical signs and physical manifestations of hypercortisolism and was generally well tolerated.”

“These data support Isturisa® as a viable long-term medical therapy option to maintain control of cortisol levels and signs and symptoms related to hypercortisolism in patients with Cushing’s disease, building on the core phase of the positive Phase III LINC 3 study, published in The Lancet Diabetes & Endocrinology in 2020,4” said Alberto M. Pedroncelli, Clinical Development & Medical Affairs Head, Global Endocrinology, Recordati AG. “Recordati Rare Diseases is committed to improving the lives of patients with this rare, debilitating and life-threatening condition. On behalf of Recordati Rare Diseases, I would like to extend our thanks to all those who have contributed to LINC 3 and the LINC clinical development programme.”

The full publication can be found here.

About Cushing’s syndrome

Cushing’s syndrome is a rare disorder caused by chronic exposure to excess levels of cortisol from either an exogenous (eg medication) or an endogenous source.5 Cushing’s disease is the most common cause of endogenous Cushing’s syndrome and arises as a result of excess secretion of adrenocorticotropic hormone from a pituitary adenoma, a tumour of the pituitary gland.5,6 There is often a delay in diagnosing Cushing’s syndrome, which consequently leads to a delay in treating patients.7 Patients who are exposed to excess levels of cortisol for a prolonged period have increased comorbidities associated with the cardiovascular and metabolic systems, which consequently reduce QoL and increase the risk of mortality.3,6 To alleviate the clinical signs associated with excess cortisol exposure, the primary treatment goal in Cushing’s syndrome is to reduce cortisol levels to normal.8,9

About LINC 3

LINC 3 is a prospective, multicentre, 48-week trial with an 8-week, double-blind, randomised withdrawal phase, with optional extension phase to evaluate the safety and efficacy of Isturisa in patients with Cushing’s disease. Assessment of mUFC response rate, change in mUFC, change in cardiovascular and metabolic-related parameters, change in patient-reported outcomes, changes in physical manifestations of hypercortisolism as well as general AEs and AEs of special interest were included as secondary endpoints. LINC 3 enrolled 137 patients with persistent or recurrent Cushing’s disease or those with de novo disease who were not candidates for surgery.4

About Isturisa®

Isturisa® is an oral inhibitor of 11β-hydroxylase (CYP11B1), which catalyses the final step of cortisol synthesis in the adrenal glands.2 Isturisa® is available as 1 mg, 5 mg and 10 mg film-coated tablets.2 Isturisa® is approved for the treatment of adult patients with endogenous Cushing’s syndrome in the EU.

Isturisa® was granted marketing authorisation by the European Commission on 9 January 2020. For detailed recommendations on the appropriate use of this product, please consult the summary of product characteristics.2

References

1. Fleseriu M, Newell-Price J, Pivonello R et al. Long-term outcomes of osilodrostat in Cushing’s disease: LINC 3 study extension The European Journal of Endocrinology 2022.

2. Isturisa® summary of product characteristics. May 2020.

3. Ferriere A, Tabarin A. Cushing’s syndrome: Treatment and new therapeutic approaches. Best Pract Res Clin Endocrinol Metab 2020;34:101381.

4. Pivonello R, Fleseriu M, Newell-Price J et al. Efficacy and safety of osilodrostat in patients with Cushing’s disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol 2020;8:748-61.

5. Lacroix A, Feelders RA, Stratakis CA et al. Cushing’s syndrome. Lancet 2015;386:913-27.

6. Pivonello R, Isidori AM, De Martino MC et al. Complications of Cushing’s syndrome: state of the art. Lancet Diabetes Endocrinol 2016;4:611-29.

7. Rubinstein G, Osswald A, Hoster E et al. Time to Diagnosis in Cushing’s Syndrome: A Meta-Analysis Based on 5367 Patients. J Clin Endocrinol Metab 2020;105.

8. Nieman LK, Biller BM, Findling JW et al. Treatment of Cushing’s syndrome: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100:2807-31.

9. Fleseriu M, Auchus R, Bancos I et al. Consensus on diagnosis and management of Cushing’s disease: a guideline update. Lancet Diabetes Endocrinol 2021;9:847-75.

Recordati Rare Diseases, the company’s EMEA headquarters are located in Puteaux, France, with global headquarter offices in Milan, Italy.

For a full list of products, please click here: www.recordatirarediseases.com/products.

Recordati, established in 1926, is an international pharmaceutical group, listed on the Italian Stock Exchange (Reuters RECI.MI, Bloomberg REC IM, ISIN IT 0003828271), with a total staff of more than 4,300, dedicated to the research, development, manufacturing and marketing of pharmaceuticals. Headquartered in Milan, Italy, Recordati has operations in Europe, Russia and the other C.I.S. countries, Ukraine, Turkey, North Africa, the United States of America, Canada, Mexico, some South American countries, Japan and Australia. An efficient field force of medical representatives promotes a wide range of innovative pharmaceuticals, both proprietary and under license, in several therapeutic areas including a specialised business dedicated to treatments for rare diseases. Recordati is a partner of choice for new product licenses for its territories. Recordati is committed to the research and development of new specialties with a focus on treatments for rare diseases. Consolidated revenue for 2021 was € 1,580.1 million, operating income was € 490.2 million and net income was € 386.0 million.

For further information:

Recordati website: www.recordatirarediseases.com

This document contains forward-looking statements relating to future events and future operating, economic and financial results of the Recordati group. By their nature, forward-looking statements involve risk and uncertainty because they depend on the occurrence of future events and circumstances. Actual results may therefore differ materially from those forecast as a result of a variety of reasons, most of which are beyond the Recordati group’s control. The information on the pharmaceutical specialties and other products of the Recordati group contained in this document is intended solely as information on the Recordati group’s activities and therefore, as such, it is not intended as medical scientific indication or recommendation, nor as advertising.

EMEA/HQ/PRO/IST/OTH/Aug-22/365

Contacts

Celine Plisson, MD

Medical Affairs Director

Telephone: +33(0)147739463

Email: PLISSON.C@recordati.com

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