~ As previously reported, LOGICS has reached its primary end point with statistical significance ~
~ Strongbridge recently submitted a new drug application (NDA) for
RECORLEV® (levoketoconazole) for the US Food & Drug Administration ~
DUBLIN, Ireland and TREVOSE, Pa., March 20, 2021 (GLOBE NEWSWIRE) – Strongbridge Biopharma plc, (Nasdaq: SBBP), a global biopharmaceutical company in a commercial stage focused on the development and commercialization of therapies for rare diseases with significant unattended needs, announced today that the detailed results of the previously reported Phase 3 LOGIC study from RECORLEV® (levocetoconazole) 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 20 to 23 March 2021.
“We are pleased to share these detailed results of the LOGICS study with the scientific community, which are based on the robust and positive data from our Phase 3 SONICS study and further demonstrate the overall benefit of RECORLEV treatment in adult patients with Cushing’s syndrome. endogenous, ”said Fredric Cohen, MD, medical director at Strongbridge Biopharma. “Together with SONICS, this data from LOGICS demonstrates substantial evidence of the effectiveness and safety of RECORLEV and serves as the basis for our New Drug Application (NDA), which was recently submitted to the US 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 assessed the safety and efficacy of RECORLEV by comparing the effect of withdrawing treatment from RECORLEV with placebo versus continuous treatment with RECORLEV on the cortisol therapeutic response established during open label RECORLEV therapy, highlighted the following:
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As previously reported, LOGICS has reached its primary endpoint with statistical significance. At the end of the randomized double-blind (RW) withdrawal phase, 54.5 percent more patients who were withdrawn to placebo experienced a loss of mean response to urinary free cortisol (mUFC) compared to those who remained on RECORLEV (p = 0.0002). Sensitivity analyzes supported the inference of the primary endpoint.
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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 in the placebo arm (p = 0.0015).
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In the RW phase, the mean time with RECORLEV was 55.5 days (range, 16-62) and in the placebo was 23.0 days (range, 16-62 days), indicating rapid loss of cortisol control after cessation RECORLEV.
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The secondary outcomes 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.
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During the titration maintenance phase, the mean change in body mass index (BMI) was -1.13 kg / mtwo. The mean change in BMI from the baseline of RW at the end of the RW phase was -0.65 kg / mtwo in the RECORLEV group, and +0.59 kg / mtwo in the placebo group (treatment difference: -1.2 kg / mtwo; P <0.0001).
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Among 80 subjects treated with RECORLEV in both combined phases, the most commonly reported adverse events (occurring in 15 percent or more individuals) were nausea, hypokalemia, headache, hypertension and diarrhea. Five percent of the individuals had a serious adverse event considered to be related to the drug. Nineteen percent had an adverse event that contributed to the discontinuation of the medication; no subject interrupted due to an adverse event in the RW phase.
On March 2, 2021, the Company announced that it had submitted an NDA for RECORLEV to the FDA for the treatment of endogenous Cushing’s syndrome. Submission is supported by positive and statistically significant results previously reported from the SONICS and LOGICS trials: two multinational Phase 3 studies designed to assess 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 exposure to elevated cortisol – usually the result of a benign pituitary gland tumor. This benign tumor tells the body to overproduce high levels of cortisol for a sustained period of time, and this usually results in undesirable physical changes. The disease is more common in adults between the ages of 30 and 50 and affects women three times more than men. Women with Cushing’s syndrome can have a variety of health problems, including menstrual problems, difficulty getting pregnant, excess male hormones (androgens), especially testosterone, which can cause hirsutism (body hair growth in a male pattern), skin oily and acne. In addition, the internal manifestations of the disease are potentially fatal. This includes metabolic changes, such as high blood sugar or diabetes, high blood pressure, high cholesterol, fragility of various tissues, including blood vessels, skin, muscles and bones, and psychological disorders such as depression, anxiety and insomnia. Left untreated, the five-year survival rate is only about 50 percent.
About the LOGICS study
The Phase 3, multinational, double-blind, placebo-controlled study, randomized withdrawal, LOGICS, patients with Cushing’s syndrome randomized with baseline mean free urinary cortisol (mUFC) at least 1.5 times the upper limit of normal ( LSN) after completing a single and open arm treatment phase of approximately 14 to 19 weeks, with RECORLEV titrated individually according to the mUFC response.
A total of 79 patients were administered during the maintenance phase of the open titration, 7 of whom had received RECORLEV previously during the SONICS study and 72 who had not received RECORLEV previously. At the beginning of the study, the median mUFC was 3.5 times the ULN, indicative of significant hypercortisolemia.
A total of 44 patients (39 who completed the titration maintenance phase and five who enrolled directly in the SONICS study) were randomized to continue RECORLEV (n = 22) or to have treatment suspended receiving a corresponding placebo regimen (n = 22) for up to 8 weeks, followed by restoration to the previous regimen using blind medication. Of the 44 randomized patients, 11 patients (25 percent) had previously received RECORLEV during the SONICS study. Patients who required rescue treatment with open label RECORLEV during the random withdrawal phase were considered to have lost the mUFC response at the visit corresponding to their first dose of the rescue drug. Patients who did not qualify for randomization were removed from open treatment before randomization and were discharged from the study.
About RECORLEV
RECORLEV® (levocetoconazole) is an inhibitor of cortisol synthesis in development for the treatment of patients with endogenous Cushing’s syndrome, a rare but serious and potentially lethal endocrine disease caused by chronic exposure to elevated cortisol. RECORLEV is the pure 2S, 4R enantiomer of ketoconazole, an inhibitor of steroidogenesis. RECORLEV has shown in two successful Phase 3 studies that it significantly suppresses 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 assess the safety and effectiveness of RECORLEV when used to treat endogenous Cushing’s syndrome. The SONICS study achieved its primary and secondary objectives, demonstrating a statistically significant rate of normalization of urinary free cortisol in six months. The LOGICS study, which achieved its primary objective, is a double-blind, placebo-controlled, randomized withdrawal study of RECORLEV that was designed to complement the long-term efficacy and safety information provided by SONICS. The ongoing long-term open OPTICS study will gather more useful information related to the long-term use of RECORLEV.
RECORLEV has received an orphan 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 biopharmaceutical company in a commercial stage focused on the development and commercialization of therapies for rare diseases with significant unmet needs. Strongbridge’s rare endocrine franchise includes RECORLEV® (levocetoconazole), an inhibitor of cortisol synthesis currently being studied in Phase 3 clinical studies for the treatment of endogenous Cushing’s syndrome, and extended release of veldoreotide, a preclinical analogue of the latest generation of somatostatin being investigated for the treatment of acromegaly and potential additional applications in other conditions susceptible to activation of the somatostatin receptor. Both RECORLEV and veldoreotide have been designated as an orphan drug by the FDA and the European Medicines Agency. The company’s rare neuromuscular franchise includes KEVEYIS® (dichlorphenamide), the first and only FDA approved treatment for hyperkalaemia, hypokalemia 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 in accordance with federal securities laws. The words “anticipate”, “estimate”, “expect”, “intend”, “can”, “plan”, “potential”, “project”, “target”, “will”, “would” or the negative of these similar terms or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All statements, except 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, results of product development efforts and management objectives for future operations. Forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from those expressed in such a 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 doctors, if approved, as treatment for any disease and the appearance of unexpected adverse events after regulatory approval and use of the product by patients. Additional risks and uncertainties related to Strongbridge and its businesses 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, also like your other files 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 assumes no obligation to update any forward-looking statements, except as required by applicable law.
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