Recorlev Helps to Keep Cholesterol in Check, LOGICS Trial Data Show
Continuous treatment with Recorlev (levoketoconazole) helped to lower blood cholesterol levels in adults with endogenous Cushing’s syndrome, according to data from the Phase 3 LOGICS trial.
Scientists at Xeris Biopharma, the company that markets Recorlev, presented the findings in the poster “Levoketoconazole in the Treatment of Endogenous Cushing’s Syndrome: a Double-Blind, Placebo-Controlled, Randomized Withdrawal Study,” during the American Association of Clinical Endocrinology (AACE) Annual Meeting, held May 12–14.
Endogenous Cushing’s syndrome is characterized by excessive levels of the stress hormone cortisol, usually due to the presence of a tumor. Cushing’s disease is a form of Cushing’s syndrome caused by a tumor in the brain’s pituitary gland.
Recorlev blocks the synthesis, or the production, of cortisol in the body. It was approved in the U.S. late last year to treat endogenous Cushing’s syndrome in adults who are not eligible for surgery to remove the disease-driving tumor or whose surgery was not effective. The therapy has been available to U.S. patients through the specialty pharmacy PANTHERx Rare since February.
Its approval was supported by data from several clinical trials, including the Phase 3 LOGICS study (NCT03277690). In this trial, participants were initially treated for several months with varying doses of Recorlev until their urine cortisol levels were within a normal range. Then, 44 participants were randomly assigned to continue with Recorlev or to switch to a placebo for eight weeks.
Top-line results, reported in 2020, showed that nearly all who switched to placebo had higher-than-normal urine cortisol levels after eight weeks, as compared to less than half of the patients who remained on Recorlev.
Data presented in the poster showed the average levels of total cholesterol decreased slightly by 0.04 millimoles per liter (mmol/L) in patients who remained on Recorlev. By contrast, cholesterol levels increased — by 0.9 mmol/L on average — in those who switched to placebo.
Levels of LDL cholesterol — a particular form commonly referred to as “bad cholesterol” and associated with a higher risk of heart disease — followed the same pattern.
After the placebo-controlled portion of the trial, all patients were treated with Recorlev for an additional eight weeks in a so-called “restoration phase.”
At the start of the restoration phase, 20 patients who had been randomized to placebo showed elevated urine cortisol levels, the company reported in a recent press release. After eight weeks back on Recorlev, urine cortisol levels dropped to a normal range in 12 (60%) of these patients.
“Treatment with [Recorlev] benefitted patients with [endogenous Cushing’s syndrome] … by normalization of [urine cortisol levels] in half of the patients and concurrent improvements in serum cholesterol,” the researchers wrote.
In a separate poster presented by Xeris at the AACE Annual Meeting, researchers reported the findings from a survey of 55 adults with endogenous Cushing’s that was conducted to better understand the disease’s impact on their lives. The poster was titled, “Patient-Reported Burden of Illness in Endogenous Cushing’s Syndrome.”
Surveyed patients had an average age of 43.4. Most of them (85%) were female and 80% had undergone surgery to treat their disease.
The most common Cushing’s symptoms reported were weight gain, muscle fatigue, and weakness. Patients reported a mean lag of nearly a decade (9.9 years) from first experiencing symptoms to attaining a diagnosis.
The average score on the CushingQoL — an assessment of health-related quality of life (HRQ0L), measured on a scale from zero (worse) to 100 (best) — was 55.8, which demonstrates “moderate HRQoL impairment,” the researchers wrote.
How symptoms affected day-to-day life was measured on a scale from one (no impact) to seven (severe impact). The disease had a substantial impact, particularly for sexual activity level and self-confidence, with average scores of 5.1 and 4.9, respectively.
Nearly 9 in 10 (89%) patients were regularly taking over-the-counter pain medications. The average pain score was a 3.6 on a scale from zero to 10, where higher scores reflect more severe pain. Problems with sleep and anxiety also were present at higher rates among Cushing’s patients than would be expected in the general U.S. population, and 70% of the patients had moderate-to-severe levels of fatigue.
Overall, these findings highlight the substantial unmet needs among people with Cushing’s syndrome.
“The patient-reported burden of illness associated with endogenous CS [Cushing’s syndrome] is multi-factorial and includes inadequate symptom control despite treatment, as demonstrated by the impact of CS on HRQoL. … There is an unmet need for interventions that provide better symptom control and improve HRQoL in patients with endogenous CS,” the researchers wrote.
“Diagnostic delays and treatments that do not sufficiently address patient symptoms may play a role in long-term patient burden,” they added.
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