Global consumer healthcare company HRA Pharma’s affiliate, Rare Diseases has published data from PROMPT, the first ever prospective study to confirm that metyrapone is both an effective and safe way to treat endogenous Cushing’s Syndrome.
The first results of the study are being published in the e-ECE conference 2020 and confirmed that metyrapone controlled 80% of the patients at week 12 with either normalisation or at least 50% decrease of urinary free cortisol.
Cushing’s Syndrome is a severe condition caused by having too much of the hormone cortisol in your body, with excess mortality and significant morbidity necessitating effective biochemical control. The syndrome affects less than 1 in 10,000 people in the EU and is therefore considered as a rare disease. Metyrapone is a steroidogenesis inhibitor and works by suppressing the last step of cortisol synthesis in the adrenal gland. It is approved in Europe for the treatment of endogenous Cushing’s Syndrome based on observational retrospective studies published over more than 50 years.
A total of 50 patients with Cushing’s Syndrome of all etiologies took part in the single arm, open-label, multicentre and international Phase III/IV study and were treated with metyrapone between April 2015 and April 2020. The patients who had three baseline 24 hours urine free cortisol values at least 50% above the upper limit of normal (ULN-165 nmol/24h) were treated with metyrapone for at least 12 weeks (W12). Patients whose mean of 3 UFC values (mUFC) did not exceed 2-fold the ULN could enter a 6-month extension period.
Metyrapone was measured over 12 weeks to achieve normal mUFC and/or serum cortisol levels. The primary efficacy endpoint was the proportion of patients with mUFC≤ULN at W12 assessed in a central laboratory using LC-MS/MS. Secondary endpoint included mUFC decrease of ≥50% at W12.
The PROMPT data showed that at the end of the first open-label period of 12 weeks, mUFC control was achieved in 80% of patients with either normalisation or at least 50% decrease of mUFC. Improvement in clinical features of the disease, in associated comorbidities and quality of life at week 12 was observed. Metyrapone is well tolerated and has a manageable safety profile.
The next set of data on the 6-month optional extension is awaiting confirmation and the full study with the final results will be published next year.
Frederique Welgryn, Managing Director of HRA Pharma Rare Diseases, says, “Cushing’s Syndrome is a chronic disease that can lead to deterioration in patients’ condition if not treated appropriately. We are thrilled to announce that this first prospective study is confirming that metyrapone is both an effective and safe way to treat endogenous Cushing’s Syndrome – with a significant reduction or normalisation of mUFC levels after 12 weeks of treatment.”
David Wright, CEO of HRA Pharma, adds, “Rare diseases are an important part of the HRA Pharma portfolio. The PROMPT study is another piece of evidence demonstrating the commitment of HRA Pharma in making effective, safe and affordable treatments for patients with rare diseases.”