Recorlev (levoketoconazole, COR-003) is an investigational treatment that Stonebridge 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 occurs when people take too much cortisol-containing medication.
Too much cortisol throws off the body’s other systems. There is a wide range of Cushing’s symptoms, including obesity, high blood sugar levels, bone problems, and fatigue.
How Recorlev works
Recorlev is a cortisol synthesis inhibitor, meaning that it keeps the adrenal gland from producing too much cortisol.
According to Stonebridge Biopharma, Recorlev is a safe, effective, and well-tolerated option for patients with endogenous Cushing’s syndrome.
Recorlev in clinical trials
A Phase 3 dose-escalation clinical trial (NCT01838551) 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 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.
Results of the SONICS study were published in September 2019 in The Lancet Diabetes & Endocrinology. The study found that 77 of the 94 patients 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 recruiting participants who are 18 or older and who have either completed the SONICS study or who have been diagnosed with endogenous Cushing’s syndrome that is not due to 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. The study is expected to last up to 51 weeks and recruit 54 participants.
In a financial update for the end of 2019, Strongbridge announced they have over 70% enrollment in the LOGICS study and they project they have enough people in titration and maintenance phases to finished enrollment. Strongbridge is projecting to complete the study in the second or third quarter of 2020 and submit a new drug application (NDA) for recorlev.
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. The study will monitor levels of mUFC, late-night salivary cortisol, and adverse effects compared to baseline for up to 3 years.
Recorlev has yet to obtain U.S. approval as a Cushing’s 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. 16, 2020
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