Strongbridge Biopharma plc Announces Presentation of New Data Comparing the In Vitro Effects of Levoketoconazole, the Active Ingredient in RECORLEV™, and Ketoconazole on Human Cortisol Production
In Vitro Data Show Preliminary Evidence That Levoketoconazole Inhibits ACTH Secretion and May Have Anti-Tumor Effect on Pituitary Adenoma Cells
First Study in Primary Human Adrenal Cells Suggests Levoketoconazole, the Pure 2S,4R Enantiomer of Ketoconazole,
Results Presented Alongside Encore SONICS Data at the 17th Annual
Led by Drs.
“These results provide important mechanistic insights that confirm prior studies demonstrating that levoketoconazole may inhibit steroidogenic enzymes more potently compared to racemic ketoconazole,” said Richard A. Feelders, M.D., Ph.D., lead investigator and endocrinologist at
In one analysis, the effects of two concentrations (0.05 and 5 µM) of levoketoconazole and ketoconazole on the steroid profile were studied in ACTH secretion-associated adrenal hyperplasia, which resulted in an accumulation of progesterone (>167% versus >96%; P < 0.01) and a decrease in cortisol (<37% versus <11%; P < 0.05) after exposure to levoketoconazole. A greater accumulation of 11-DOC (the immediate precursor of cortisol) was observed with racemic ketoconazole (P < 0.01 versus levoketoconazole). Under ACTH stimulation, steroid inhibition dose-response results indicate greater potency of levoketoconazole compared to racemic ketoconazole.
A separate analysis showed that when corticotroph pituitary tumor cells were treated with levoketoconazole and racemic ketoconazole, only levoketoconazole demonstrated inhibition of ACTH secretion after just three days of treatment (P = 0.0436 vs. racemic ketoconazole), whereas both levoketoconazole and racemic ketoconazole inhibited ACTH secretion after seven days of treatment. Furthermore, two primary ACTH-secreting corticotroph pituitary adenoma cultures were examined for cell amount and ACTH secretion after seven days of treatment with levoketoconazole and racemic ketoconazole. Levoketoconazole significantly inhibited cell proliferation in one culture (P < 0.001 versus control), and a significant difference between levoketoconazole and racemic ketoconazole was observed in both cultures, suggesting a stronger effect by levoketoconazole.
- Oral Presentation #OC24 – Levoketoconazole, the Single 2S,4R Enantiomer of Ketoconazole, is a Potential Novel Steroid Synthesis Inhibitor for Medical Treatment of Cushing’s Syndrome; Richard A. Feelders; NAPACA Oral Communications OC23-28, Nov. 23, 2018, 11:40 –
- Poster #PP57: Safety and Efficacy of Levoketoconazole in Cushing Syndrome: Initial Results From the Phase 3 SONICS Study; Rosario Pivonello; Poster Guided Session/Networking,
Nov. 22, 2018, 11:15 – 12:45 CET
About Endogenous Cushing’s Syndrome
Endogenous Cushing’s syndrome (CS) is a rare but serious and potentially lethal endocrine disease caused by chronic elevated cortisol exposure. Most people with CS have a variety of signs and symptoms – many of which, when they occur by themselves, are common and do not necessarily point to an underlying disease; this makes recognition of CS difficult. Common presenting symptoms include weight gain or obesity, fatigue, muscle weakness, headaches, mood or sleep disturbances, facial rounding or redness, excess body hair growth in women or baldness in men, thinned skin with stretch marks, easy bruising and other skin changes including acne, mood or sleep disturbances and irregular periods or loss of libido. Patients are often found by their doctors to have new-onset or worsening of high blood pressure, abnormal levels of blood lipids, such as cholesterol, polycystic ovaries and abnormal blood glucose or diabetes. People with uncontrolled disease are seriously ill and have a 2- to 4-fold higher mortality rate than age- and gender-matched controls, mainly due to metabolic and cardiovascular complications. Treatment options for CS include surgery, radiation therapy, and medical treatment. CS most commonly affects adults ages 20-50 and is more prevalent in females, accounting for about 70 percent of all cases.
About Strongbridge Biopharma
Strongbridge Biopharma is a global commercial-stage biopharmaceutical company focused on the development and commercialization of therapies for rare diseases with significant unmet needs. Strongbridge's rare endocrine franchise includes RECORLEV™ (levoketoconazole), a cortisol synthesis inhibitor currently being studied in Phase 3 clinical studies for the treatment of endogenous Cushing's syndrome, and veldoreotide extended release, a pre-clinical next-generation somatostatin analog being investigated for the treatment of acromegaly and potential additional applications in other conditions amenable to somatostatin receptor activation. Both RECORLEV and veldoreotide have received orphan drug designation from the FDA and the European Medicines Agency. The Company’s rare neuromuscular franchise includes KEVEYIS® (dichlorphenamide), the first and only FDA-approved treatment for hyperkalemic, hypokalemic, and related variants of primary periodic paralysis. KEVEYIS has orphan drug exclusivity in the
This press release contains forward-looking statements within the meaning of the federal securities laws. The words "anticipate," "estimate," "expect," "intend," "may," "plan," "potential," "project," "target," "will," "would," or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All statements, other than statements of historical facts, contained in this press release, are forward-looking statements, including statements related to the potential advantages of RECORLEV, the release of additional planned analyses of the SONICS study, Strongbridge's strategy, plans, status and results of SONICS and other clinical trials, outcomes of product development efforts and objectives of management for future operations. Forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from those expressed in such statement, including risks and uncertainties associated with clinical development and the regulatory approval process, the reproducibility of any reported results showing the benefits of RECORLEV, the adoption of RECORLEV by physicians, if approved, as treatment for any disease and the emergence of unexpected adverse events following regulatory approval and use of the product by patients. Additional risks and uncertainties relating to Strongbridge and its business can be found under the heading “Risk Factors” in Strongbridge’s Annual Report on Form 10-K for the year ended
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Source: Strongbridge Biopharma plc