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Long-acting pasireotide improves clinical signs and quality of life in Cushing’s disease: results from a phase III study

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Abstract

Purpose

Cushing’s disease (CD) is associated with significant clinical burden, increased mortality risk, and impaired health-related quality of life (HRQoL). This analysis explored the effect of long-acting pasireotide on clinical signs of hypercortisolism and HRQoL in a large subset of patients with CD.

Methods

In this phase III study (clinicaltrials.gov: NCT01374906), 150 adults with CD and a mean urinary free cortisol (mUFC) level between 1.5 and 5.0 times the upper limit of normal (ULN) started long-acting pasireotide 10 or 30 mg every 28 days with dose increases/decreases permitted based on mUFC levels/tolerability (minimum/maximum dose: 5/40 mg). Changes in clinical signs of hypercortisolism and HRQoL were assessed over 12 months of treatment and were stratified by degree of mUFC control for each patient.

Results

Patients with controlled mUFC at month 12 (n = 45) had the greatest improvements from baseline in mean systolic (− 8.4 mmHg [95% CI − 13.9, − 2.9]) and diastolic blood pressure (− 6.0 mmHg [− 10.0, − 2.0]). Mean BMI, weight, and waist circumference improved irrespective of mUFC control. Significant improvements in CushingQoL total score of 5.9–8.3 points were found at month 12 compared with baseline, irrespective of mUFC control; changes were driven by improvements in physical problem score, with smaller improvements in psychosocial score.

Conclusions

Long-acting pasireotide provided significant improvements in clinical signs and HRQoL over 12 months of treatment, which, in some cases, occurred regardless of mUFC control. Long-acting pasireotide represents an effective treatment option and provides clinical benefit in patients with CD.

Clinical trial registration number

NCT01374906

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Acknowledgements

This study was funded by Novartis Pharma AG. Funding for this manuscript was provided by Novartis Pharmaceuticals Corporation. We thank Robert Jenn PhD, Mudskipper Business Limited, for his medical editorial assistance. We also thank the site investigators, study coordinators, and patients who participated in the trial.

Author information

Authors and Affiliations

  1. Centre hospitalier de l’Université de Montréal, 3840 Saint-Urbain, Montreal, H2W1T8, Canada

    A. Lacroix

  2. University of São Paulo Medical School, São Paulo, Brazil

    M. D. Bronstein

  3. Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany

    J. Schopohl

  4. Hacettepe University, Ankara, Turkey

    T. Delibasi

  5. Division of Endocrinology, Diabetes and Metabolism, and Pituitary Center, Johns Hopkins University, Baltimore, MD, USA

    R. Salvatori

  6. Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China

    Y. Li

  7. University of Michigan, Ann Arbor, MI, USA

    A. Barkan

  8. Nagoya Medical Center, National Hospital Organization, Nagoya, Japan

    N. Suzaki

  9. Novartis Pharma AG, Basel, Switzerland

    L. Tauchmanova & C.-E. Ortmann

  10. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    S. Ravichandran

  11. ENDOC Center for Endocrine Tumors, Hamburg, Germany

    S. Petersenn

  12. Università Federico II di Napoli, Naples, Italy

    R. Pivonello

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  1. A. Lacroix
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  2. M. D. Bronstein
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  3. J. Schopohl
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  11. S. Ravichandran
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Corresponding author

Correspondence to A. Lacroix.

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Conflict of interest

André Lacroix has received funding as an investigator or consultant from Novartis, Cortendo, Strongbridge Biopharma, and GLWL Research, Inc. Marcello D Bronstein has received consulting fees from Chiasma, Ipsen, Novartis, and Pfizer, speaker fees from Novartis and Ipsen, and research grants from Novartis and Ipsen, and is a principal investigator of clinical trials supported by Novartis and Ipsen. Jochen Schopohl has received lecture fees from Novartis, Ipsen, and Pfizer, and has served on advisory boards for Novartis and Ipsen. Tuncay Delibasi has no conflicts of interest to disclose. Roberto Salvatori has received grants as a clinical investigator from Novartis and Strongbridge Biopharma, consulting fees from Novo Nordisk and Novartis, and personal fees as an advisory board member from SteroTherapeutics. Yiming Li has received lecture fees from Novartis and Ipsen. Ariel Barkan has received an investigator-initiated grant from Novartis (paid to the University of Michigan). Noriyuki Suzaki has received speaker fees from Novartis and a research grant from Chugai Pharmaceutical Co Ltd. Libuse Tauchmanova, Christine-Elke Ortmann, and Shoba Ravichandran are employees of Novartis. Stephan Petersenn has served as a lecturer for Ipsen, Novartis, and Pfizer, and as an advisory board member for Ipsen and Novartis. Rosario Pivonello has received grants and personal fees from Novartis, Pfizer, HRA Pharma, Viropharma, Shire, and Ipsen, personal fees from Ferring and Italfarmaco, and grants from Corcept Therapeutics, Cortendo AB, and IBSA.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Lacroix, A., Bronstein, M.D., Schopohl, J. et al. Long-acting pasireotide improves clinical signs and quality of life in Cushing’s disease: results from a phase III study. J Endocrinol Invest 43, 1613–1622 (2020). https://doi.org/10.1007/s40618-020-01246-0

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  • DOI: https://doi.org/10.1007/s40618-020-01246-0

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