Strongbridge Reports Positive Results from Pivotal Cushing’s Syndrome Study

Rare Daily Staff

Strongbridge Biopharma reported positive results from its multinational, pivotal phase 3 study evaluating its experimental therapy Recorlev for the treatment of endogenous Cushing’s syndrome, a rare, serious, and potentially lethal endocrine disorder.

Endogenous Cushing’s syndrome is caused by chronic elevated cortisol exposure—often the result of a benign tumor of the pituitary gland. This benign tumor tells the body to overproduce high levels of cortisol for a sustained period, and this often results in undesirable physical changes. The disease is most common among adults between the ages of 30 to 50, and it affects women three times more often than men.

Women with Cushing’s syndrome may experience a variety of health issues including menstrual problems, difficulty becoming pregnant, excess male hormones (androgens), primarily testosterone, which can cause hirsutism (growth of coarse body hair in a male pattern), oily skin, and acne. Additionally, the internal manifestations of the disease are potentially life threatening. These include metabolic changes such as high blood sugar, or diabetes, high blood pressure, high cholesterol, fragility of various tissues including blood vessels, skin, muscle and bone, and psychologic disturbances such as depression, anxiety and insomnia. Untreated, the five-year survival rate is only approximately 50 percent.

Recorlev is an experimental cortisol synthesis inhibitor in development for the treatment of patients with endogenous Cushing’s syndrome. It has demonstrated, in two successful phase 3 studies, to significantly suppress serum cortisol and has the potential to be a next-generation cortisol inhibitor.

“The reporting of top-line data from our phase 3 LOGICS study marks a critical milestone for the company,” said John Johnson, CEO of Strongbridge Biopharma. The company said the results, coupled with previously reported positive results from its phase 3 SONICS study, will support a New Drug Application in the United States, which the company expects to submit to the U.S. Food and Drug Administration in the first quarter of 2021.

The phase 3 LOGICS study accepted Cushing’s syndrome patients with baseline mean urinary free cortisol (mUFC) at least 1.5 times the upper limit of normal (ULN). Patients who had previously completed the phase 3 SONICS study were also permitted to be considered for entry into the LOGICS study.

Prior to the randomized-withdrawal phase, seventy-nine (79) study participants entered a single-arm, open-label titration and maintenance phase of approximately 14 to 19 weeks. Forty-four (44) patients (including five who were randomized directly from SONICS) were entered into the 8-week randomized-withdrawal portion of the trial, with twenty-two (22) patients randomized to the Recorlev arm and twenty-two (22) patients to the placebo arm. Forty-three (43) patients completed the randomized-withdrawal phase.

At the end of the randomized-withdrawal phase of the LOGICS study, 54.5 percent more patients who were withdrawn to placebo had a loss of mUFC response as compared with those who remained on Recorlev (95.5 percent vs 40.9 percent). All 21 patients who lost response after being randomized to placebo received early rescue treatment within the 8-week randomized-withdrawal phase with a median time to early rescue of 22 days.

The secondary endpoint of normalization of mUFC at the end of the randomized-withdrawal phase was also highly statistically significant with 45.5 percent more patients treated with Recorlev maintaining mUFC normalization in the active arm than the placebo arm (50.0 percent vs 4.5 percent respectively).

In general, Recorlev was well tolerated, with 19 percent of the 79 patients initially dosed discontinuing during titration-maintenance due to adverse events (AEs). None of the 44 randomized patients discontinued because of AEs. The most common AEs reported in both phases (titration-maintenance and randomized-withdrawal) among 80 patients who received Recorlev continuously were nausea (29 percent), hypokalemia (28 percent), headache (21 percent), hypertension (19 percent), and diarrhea (15 percent). During the randomized-withdrawal phase, the AEs most commonly reported in at least 5 percent of patients, and with a higher frequency in the Recorlev group as compared with the placebo group, were hypertension, nausea, and fatigue.

Photo: John Johnson, CEO of Strongbridge Biopharma