Strongbridge Biopharma plc Announces RECORLEV™ (levoketoconazole) Phase 3 SONICS Data Published in The Lancet Diabetes & Endocrinology

~ RECORLEV Resulted in Sustained Improvements in Urinary Free Cortisol (UFC) and Provided Clinical Benefit, As Demonstrated By Improvements in Comorbidities and Characteristic Signs and Symptoms of Cushing’s Syndrome ~

~ RECORLEV Was Generally Well-Tolerated, With No Unexpected Safety Signals Observed ~

DUBLIN, Ireland and TREVOSE, Pa., Sept. 19, 2019 (GLOBE NEWSWIRE) -- Strongbridge Biopharma plc, (Nasdaq: SBBP), a global commercial-stage biopharmaceutical company focused on the development and commercialization of therapies for rare diseases with significant unmet needs, today announced that comprehensive results from the positive pivotal Phase 3 SONICS study of RECORLEV™ (levoketoconazole) for the potential treatment of endogenous Cushing’s syndrome were published online in The Lancet Diabetes & Endocrinology.

“The Phase 3 SONICS study demonstrated RECORLEV, the 2S,4R enantiomer of ketoconazole, was safe and effective in a representative population of patients with endogenous Cushing’s syndrome,” said Maria Fleseriu, M.D., FACE, professor of Medicine and Neurological Surgery and director of the Oregon Health Sciences University Northwest Pituitary Center and principal investigator of the study. “Importantly, treatment with RECORLEV was shown to be effective for reducing and normalizing mUFC concentrations and biomarkers of cardiovascular risk, as well as improving clinical signs and quality of life in patients with endogenous Cushing’s syndrome. These data are highly encouraging given medical needs remain very high for this rare endocrine disorder, despite the availability of approved treatments.”

SONICS enrolled 94 patients experiencing a mean urinary free cortisol (mUFC) of 671∙4 nmol/24 hours (243∙3 μg/24 hours), which is nearly five times the upper normal limit (UNL). Seventy seven patients advanced into the six-month maintenance phase, and 61 patients completed this phase of the study. The SONICS study met its primary endpoint, with 30 percent of patients achieving mUFC normalization at the end of the maintenance phase among the intent-to-treat (ITT) population (n=94), without a dose increase (p=0.015 vs null hypothesis of ≤20%).

“Publication of these data in a prestigious journal such as The Lancet Diabetes & Endocrinology underscore their importance to the endocrinology community,” said Fredric Cohen, M.D., chief medical officer of Strongbridge Biopharma. “We look forward to continuing to advance our clinical development program for RECORLEV with top-line data expected from LOGICS, our second Phase 3 trial, at the end of the first quarter of 2020, and NDA submission at the end of the third quarter of 2020.”

The manuscript, entitled “Safety and efficacy of levoketoconazole in the treatment of endogenous Cushing’s syndrome (SONICS): A Phase 3, open-label, single-arm trial,” includes mUFC responder analyses which found:

• For the patients who advanced into the maintenance phase, 81 percent had achieved mUFC normalization by the end of the dose titration phase
• 36 percent of patients achieved normalization of mUFC during the maintenance phase, regardless of dose increase, ITT analysis
• 46 percent of patients achieved a 50 percent or more decrease or normalization of mUFC during the maintenance phase, regardless of dose increase, ITT analysis
• 62 percent of maintenance phase completers had normalized mUFC at month six based on 55 maintenance phase completers with both baseline and month six mUFC data available

For key secondary endpoints of cardiovascular risk biomarkers, such as fasting glucose, weight and LDL-cholesterol, RECORLEV demonstrated statistically significant and clinically meaningful mean improvements from baseline at the end of the maintenance phase. RECORLEV was generally well-tolerated during the dose titration and maintenance phases of the study and no unexpected safety signals were observed. The most common adverse effects were nausea (32%) and headache (28%). Adverse events leading to discontinuation of treatment occurred in 12 of the 94 patients (13%) enrolled.

The full manuscript can be accessed online at: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30313-4/fulltext.

About the SONICS Study
SONICS is an open-label, Phase 3 study of RECORLEV as a treatment for endogenous Cushing’s syndrome that enrolled 94 patients at centers in North America, Europe and the Middle East. Following a screening phase, SONICS has three treatment phases:

(1) Dose Titration Phase: Patients started RECORLEV at 150 mg twice daily (300 mg total daily dose) and titrated in 150 mg increments with the goal of achieving a therapeutic dose – a dose resulting in mUFC normalization – at which point titration was stopped; (2) Maintenance Phase: The dose was fixed and should not have been changed other than for safety reasons or loss of efficacy. At the end of the six-month maintenance phase, the mUFC response rate was measured; and (3) Extended Evaluation Phase: Patients continued on RECORLEV for another six months to evaluate long-term safety and tolerability and explore efficacy durability.

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 United States.

About RECORLEV
RECORLEV™ (levoketoconazole) is an investigational cortisol synthesis inhibitor in development for the treatment of patients with endogenous Cushing’s syndrome, a rare but serious and potentially lethal endocrine disease caused by chronic elevated cortisol exposure. RECORLEV is the pure 2S,4R enantiomer of ketoconazole, a steroidogenesis inhibitor. RECORLEV is believed to significantly suppress serum cortisol in healthy subjects and has the potential to be a next-generation cortisol inhibitor.

The Phase 3 program for RECORLEV consists of SONICS and LOGICS: two multinational studies designed to evaluate the safety and efficacy of RECORLEV when used to treat endogenous Cushing’s syndrome. The SONICS study met its primary and secondary endpoints, demonstrating a statistically significant normalization rate of urinary free cortisol (UFC) at six months. The ongoing LOGICS study is a double-blind, placebo-controlled randomized-withdrawal study of RECORLEV that is designed to supplement the long-term efficacy and safety information supplied by SONICS.

RECORLEV has received orphan drug designation from the FDA and the European Medicines Agency for the treatment of endogenous Cushing's syndrome.

Forward-Looking Statements

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, Strongbridge’s strategy, plans, status and results of clinical trials, 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 December 31, 2018 and subsequent filings with the SEC. These forward-looking statements are based on current expectations, estimates, forecasts and projections and are not guarantees of future performance or development and involve known and unknown risks, uncertainties and other factors. The forward-looking statements contained in this press release are made as of the date of this press release, and Strongbridge Biopharma does not assume any obligation to update any forward-looking statements except as required by applicable law.

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