Recorlev (levoketoconazole, COR-003) is an investigational treatment that Strongbridge Biopharma is developing for endogenous Cushing’s syndrome. Endogenous means that symptoms occur because the body is producing too much of the hormone cortisol. In contrast, exogenous Cushing’s syndrome occurs when people take too much cortisol-containing medication.
Too much cortisol throws off the body’s other systems causing symptoms such as obesity, high blood sugar levels, bone problems, and fatigue.
Recorlev is a cortisol synthesis inhibitor, meaning that it keeps the adrenal glands from producing too much cortisol.
Recorlev in clinical trials
A Phase 3 clinical trial (NCT01838551) to test the efficacy of ascending doses of Recorlev was completed in 2018. The international open-label trial, called SONICS, involved 94 participants with new, persistent, or recurrent Cushing’s syndrome who were not candidates for radiation therapy or surgery and had urinary cortisol levels at least 1.5 times the normal range.
Each participant received increasing oral doses of Recorlev for up to 21 weeks until the mean levels of cortisol in the urine — known as mean urinary free cortisol, or mUFC — fell into a normal range or they reached the maximum dosage of 600 mg twice daily.
Once a therapeutic dose was established, participants continued to take that dose for six months. The goal was to identify a range of safe and effective doses that could reduce urinary free cortisol by the end of the six-month maintenance period.
The results of the SONICS study were published in September 2019 in The Lancet Diabetes & Endocrinology. A total of 77 out of the 94 participants completed the dose-escalation phase and moved into the maintenance phase. By the end of the trial, 29 out of 94 patients were able to maintain normal mUFC levels without dose increases during the maintenance phase.
A second global Phase 3 clinical trial (NCT03277690), named LOGICS, is currently recruiting an estimated 54 participants ages, 18 or older in the U.S., Europe, and Israel. Participants must have either completed the SONICS study or been diagnosed with endogenous Cushing’s syndrome not caused by adrenal or pituitary cancer.
This is a double-blind trial designed to assess the effectiveness, safety, and tolerability of Recorlev, as well as how the body absorbs and processes it. After a period of taking Recorlev, either in the SONICS study or in this study, some participants will be switched to a placebo and some will remain on the medication. Researchers will assess how frequently Recorlev stops working in patients who have had a period of withdrawal versus patients who have remained on the medication. Response to treatment will be assessed by measuring mUFC.
In a financial update for the end of 2019, Strongbridge announced it reached over 70% enrollment in the LOGICS study. The company is projecting to complete the study in the second half of 2020 and submit a new drug application (NDA) for Recorlev to the U.S. Food and Drug Administration (FDA).
Strongbridge has also started an open-label Phase 3 extension study (NCT03621280), called OPTICS, for participants who have completed either the SONICS or LOGICS studies. This study will monitor levels of mUFC, late-night salivary cortisol, and adverse effects compared to baseline for up to three years.
Recorlev has yet to obtain U.S. approval as a Cushing’s disease treatment, but it does have orphan drug status in both the U.S. and Europe. Orphan drugs are medications that have shown potential as treatments for rare medical conditions. The orphan designation makes it easier for drug developers to get through the approval process.
Last updated: Jan. 22, 2020
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