Strongbridge Biopharma plc Presents Detailed Results from Pivotal Phase 3 LOGICS Study of RECORLEV® (levoketoconazole) for the Treatment of Endogenous Cushing’s Syndrome at the 2021 Annual Meeting of the Endocrine Society (ENDO)

~ As Previously Reported, LOGICS Met its Primary Endpoint with Statistical Significance ~

~ Strongbridge Recently Submitted a New Drug Application (NDA) for
RECORLEV^® (levoketoconazole) to the U.S. Food & Drug Administration ~

DUBLIN, Ireland and TREVOSE, Pa., March 20, 2021 (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 detailed results from the previously reported Phase 3 LOGICS study of RECORLEV^® (levoketoconazole) in patients with endogenous Cushing’s syndrome were presented in a poster session at the Annual Meeting of the Endocrine Society (ENDO), being held virtually from March 20 – 23, 2021.

“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,” said Fredric Cohen, M.D., chief medical officer of Strongbridge Biopharma. “Together with SONICS, these LOGICS data demonstrate substantial evidence of RECORLEV efficacy and safety and serve as the basis of our New Drug Application (NDA), which was recently submitted to the U.S. Food and Drug Administration (FDA). We remain confident that, if approved, RECORLEV may be an important new treatment option for patients with endogenous Cushing’s syndrome.”

The poster presentation, which further evaluated the safety and efficacy of RECORLEV by comparing the effect of withdrawing RECORLEV treatment to placebo versus continuing treatment with RECORLEV on the cortisol therapeutic response established during open-label RECORLEV therapy, highlighted the following:

• As previously reported, LOGICS met its primary endpoint with statistical significance. At the end of the double-blind randomized-withdrawal (RW) phase, 54.5 percent more patients who were withdrawn to placebo had a loss of mean urinary free cortisol (mUFC) response as compared with those who remained on RECORLEV (p = 0.0002). Sensitivity analyses supported the primary endpoint inference.
• The key secondary endpoint of mUFC normalization at the end of the RW phase was also statistically significant with 45.5 percent more patients treated with RECORLEV maintaining mUFC normalization in the active arm than the placebo arm (p = 0.0015).
  • In the RW phase, median time on RECORLEV was 55.5 days (range, 16–62) and on placebo was 23.0 days (range, 16–62 days), indicating rapid loss of cortisol control upon RECORLEV cessation.
• The secondary endpoints of mean changes from the RW baseline to the end of the RW phase for total and LDL-cholesterol were significantly different (p<0.01) between treatment groups, with mean treatment differences of 37.1 and 25.1 mg/dL, respectively.
• During the titration-maintenance phase, mean change in body mass index (BMI) was -1.13 kg/m². Mean change in BMI from RW baseline to end of RW phase was -0.65 kg/m² in the RECORLEV group, and +0.59 kg/m² in the placebo group (treatment difference: -1.2 kg/m²; P<0.0001).
• Among 80 subjects treated with RECORLEV in both phases combined, the most commonly reported adverse events (occurring in 15 percent or more subjects) were nausea, hypokalemia, headache, hypertension, and diarrhea. Five percent of subjects had a serious adverse event considered to be drug related. Nineteen percent had an adverse event that contributed to drug discontinuation; no subjects discontinued due to adverse event in the RW phase.

On March 2, 2021, the Company announced it had submitted an NDA for RECORLEV for the treatment of endogenous Cushing’s syndrome to the FDA. The submission is supported by previously reported positive and statistically significant results of the SONICS and LOGICS trials: two Phase 3 multinational studies designed to evaluate the safety and efficacy of RECORLEV when used to treat adults with endogenous Cushing’s syndrome.

About Cushing’s Syndrome
Endogenous Cushing’s syndrome is a rare, serious and potentially lethal endocrine disease 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 of time, 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.

About the LOGICS Study
The Phase 3, multinational, double-blind, placebo-controlled, randomized-withdrawal study, LOGICS, randomized Cushing’s syndrome patients with baseline mean urinary free cortisol (mUFC) at least 1.5 times the upper limit of normal (ULN) following completion of a single-arm, open-label treatment phase of approximately 14 to 19 weeks, with RECORLEV individually titrated according to mUFC response.  

A total of 79 patients were dosed during the open-label titration-maintenance phase, 7 of whom had previously received RECORLEV during the SONICS study, and 72 who had not previously received RECORLEV. At study baseline, the median mUFC was 3.5 times the ULN, indicative of significant hypercortisolemia.

A total of 44 patients (39 who had completed the titration-maintenance phase and five who directly enrolled from the SONICS study), were randomized to either continue RECORLEV (n=22) or to have treatment withdrawn by receiving a matching placebo regimen (n=22) for up to 8 weeks, followed by restoration to the prior regimen using blinded drug. Of the 44 patients randomized, 11 patients (25 percent) had previously received RECORLEV during the SONICS study.  Patients who required rescue treatment with open-label RECORLEV during the randomized-withdrawal phase were considered to have lost mUFC response at the visit corresponding to their first dose of rescue medication. Patients who did not qualify for randomization were removed from open-label treatment prior to randomization and excused from the study. 

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 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 Phase 3 program for RECORLEV includes 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 at six months. The LOGICS study, which met its primary endpoint, 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. The ongoing long-term open label OPTICS study will gather further useful information related to the long-term use of RECORLEV.

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

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 preclinical 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.

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 potential advantages of RECORLEV, Strongbridge’s strategy, plans, 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 December 31, 2020 and its subsequent Quarterly Reports on Form 10-Q, as well as its other 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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