Recorlev Also Helps Lower Cholesterol and Body Fat, Phase 3 Trial Finds

Recorlev (levoketoconazole), Strongbridge Biopharma’s oral candidate to treat endogenous Cushing’s syndrome, was superior to a placebo at lowering cholesterol levels and body mass index, a measure of body fat, according to newly released data from the pivotal Phase 3 LOGICS trial.

These findings, concerning most of the trial’s secondary goals, added to top-line data released last year that showed Recorlev met the study’s main goal, that of normalizing urine cortisol levels in treated patients.

Data from LOGICS (NCT03277690), as well as the SONICS Phase 3 trial (NCT01838551), supported Strongbridge’s recent application to the U.S. Food and Drug Administration (FDA) requesting that Recorlev be approved to treat endogenous Cushing’s syndrome.

“Together with SONICS, these LOGICS data demonstrate substantial evidence of Recorlev efficacy and safety,” Fredric Cohen, MD, chief medical officer of Strongbridge Biopharma, said in a press release. “We remain confident that, if approved, Recorlev may be an important new treatment option for patients with endogenous Cushing’s syndrome.”

Rosario Pivonello, MD, with the Università Federico II di Napoli in Italy, presented these findings at the 2021 Annual Meeting of the Endocrine Society (ENDO) in the poster titled “Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushing’s Syndrome (LOGICS): Results From a Double-Blind, Placebo-Controlled, Randomized Withdrawal Study.”

Recorlev is an oral suppressor of cortisol production, which is excessive in patients with endogenous Cushing’s syndrome, being developed by Strongbridge to treat the disease.

LOGICS, which assessed the safety, tolerability, and effectiveness of Recorlev in adult patients, followed the launch of SONICS. That trial also met its primary goal, demonstrating that Recorlev was superior to a placebo at normalizing cortisol levels in patients’ urine after six months of maintenance therapy, without any dose increase.

LOGICS opened with 79 patients given Recorlev in an open-label titration and maintenance phase for several months, to determined their best dose. It included some people previously treated in the SONICS trial.

Of this group, 44 were determined eligible to advance to the trial’s next phase and be randomly assigned, 1:1, to either Recorlev tablets (up to 1200 mg daily) or a placebo tablet — as a treatment withdrawal group — for about eight weeks. Eleven of these 44 patients (25%) were recruited from SONICS.

Previously reported top-line data showed that, by the end of the randomized phase, significantly fewer patients on continuous Recorlev saw their urine cortisol levels rise (40.9%), compared with those who had moved to a placebo (95.5%). This corresponded to a reduction of 54.5% in favor of Recorlev.

Data also showed that a key secondary trial goal was achieved, with 45.5% more patients on continuous Recorlev use reaching normal urine cortisol levels by this trial phase end than did those moved to a placebo (50.0% vs. 4.5%). This difference was found to be statistically significant.

During the randomization phase, patients staying with Recorlev were treated for a median of 55.5 days, and those given a placebo for 23 days, supporting that cortisol control is lost rapidly upon stopping Recorlev.

Newly released interim trial data found that placebo-group patients also lost the cholesterol-lowering benefits of Recorlev. Significantly higher levels of total and low-density lipoprotein (LDL)-cholesterol (also called “bad-cholesterol”) were seen in patients withdrawn from treatment by randomization compared with those who weren’t:  a difference of 35.6 mg/dL in total cholesterol and 25.0 mg/dL in LDL-cholesterol between these groups.

This was accompanied by a statistically significant increase in body mass index (BMI), a measure of body fat, in patients on a placebo (+0.59 kg/m²).  BMI decreased over this trial phase (-0.65 kg/m²) in those continuously treated with Recorlev.

Nausea, low potassium blood levels (hypokalemia), headache, high blood pressure, and diarrhea were the most common (reported in at least 15% of patients) adverse side effects associated with Recorlev. Among 80 people treated in both study parts, 19% stopped with Recorlev due to side effects. None of the 44 patients who in moved into the trial’s randomized phase discontinued its use.

“We are pleased to share these detailed results of the LOGICS study with the scientific community, which build upon the robust and positive data from our Phase 3 SONICS study and further demonstrate the overall treatment benefit of Recorlev in adult patients with endogenous Cushing’s syndrome,” Cohen said.

Recorlev’s long-term safety and effectiveness is being evaluated in the Phase 3 OPTICS study (NCT03621280). The open-label trial, which enrolled endogenous Cushing’s syndrome patients who finished either SONICS, LOGICS, or both studies, is due to conclude in June 2023.