New Phase 3 Data Further Support Recorlev’s Ability to Safely Lower Cortisol Levels in Cushing’s Patients

Strongbridge Biopharma released additional positive results from a Phase 3 trial evaluating whether the company’s investigational therapy Recorlev (levoketoconazole) is safe and effective for people with endogenous Cushing’s syndrome.

The latest results were presented in the scientific poster “Safety and Efficacy of Levoketoconazole in Cushing Syndrome:  Initial Results From the Phase 3 SONICS Study,\” at the 18th Annual Congress of the European NeuroEndocrine Association (ENEA), which took place in Wrocław, Poland, last month.

The SONICS study (NCT01838551) was a multi-center, open-label Phase 3 trial evaluating Recorlev’s safety and effectiveness in 94 patients with endogenous Cushing’s syndrome.

The trial consisted of three parts: a dose-escalation phase to determine the appropriate Recorlev dose that achieved normalization of cortisol levels; a maintenance phase in which patients received the established dose for six months; and a final extended phase, in which patients were treated with Recorlev for an additional six months, with the possibility of dose adjustments.

Its primary goal was a reduction in the levels of cortisol in the patients’ urine after six months of maintenance treatment, without any dose increase during that period. Among secondary goals was a reduction in the characteristically high risk of cardiovascular disease in these people, through the assessment of multiple cardiovascular risk markers.

Strongbridge announced top-line results of the SONICS study in August, which showed that the trial had reached its primary and secondary goals. It concluded last month.

After six months of maintenance therapy, Recorlev successfully lowered to normal the levels of cortisol in 30% of patients without a dose increase. It also led to statistically and clinically significant reductions in cardiovascular risk biomarkers, including blood sugar, cholesterol levels, body weight, and body mass index.

Maria Fleseriu, MD, director of the Oregon Health Sciences University Northwest Pituitary Center, presented additional and detailed results of SONICS at the congress.

Additional analyses showed that among the 77 patients who completed the dose-escalation phase and entered the study’s maintenance phase, 81% had their cortisol levels normalized.

At the end of the six months of maintenance treatment, 29 (53%) of the 55 patients who had their cortisol levels assessed at the beginning of the study and at the end of the maintenance phase had achieved normalization of cortisol levels, regardless of dose increase.

Among all patients who completed maintenance treatment (including patients with some missing data) and regardless of dose increase, 38% had achieved normalization of cortisol levels and 48% recorded a 50% or more decrease or normalization.

The results also highlighted that Recorlev substantially reduced patients’ cortisol levels regardless of their levels at the study’s beginning (which were on average about five-fold higher than the upper limit of normal). In those patients with the highest levels of cortisol in their urine, Recorlev led to a median reduction of more than 80%.

As previously reported, Recorlev was found to be generally well-tolerated, with no new safety concerns, and only 12 participants (12.8%) stopped treatment due to adverse events.

Ten patients had three- or five-fold increased levels of alanine aminotransferase — a liver enzyme used to assess liver damage — which were fully resolved without further complications. These liver-related adverse events “were all noted in the first 60 days, thus suggesting a timeline interval for monitoring,” Fleseriu said in a press release.

“We continue to be encouraged by the positive efficacy results of SONICS and the overall benefit-to-risk profile of Recorlev and look forward to sharing additional planned analyses from the study in the near future,” said Fredric Cohen, Strongbridge’s chief medical officer.

From https://cushingsdiseasenews.com/2018/11/01/new-data-from-phase-3-trial-supports-recorlev-ability-to-safely-treat-cushings-syndrome/

Drug trial begins for Cushing’s syndrome therapy

Participant enrollment has concluded for a phase 3 trial investigating the safety and efficacy of levoketoconazole, a cortisol synthesis inhibitor, for the treatment of endogenous Cushing’s syndrome, according to a press release from Strongbridge Biopharma, the drug’s developer.

The single-arm, open-label SONICS study will include the 90 enrolled participants and may allow a small number of other patients to enroll also, according to the release.

After titration to a therapeutic dose of levoketoconazole (Recorlev), participants will maintain treatment for 6 months, the primary efficacy endpoint. Longer-term evaluation for safety will extend to 1 year. A planned 6-month double blind, placebo-controlled, randomized withdrawal extension, dubbed LOGICS, will include approximately half of the participants from SONICS.

“The need for a safe and effective, next-generation cortisol synthesis inhibitor, such as Recorlev, in the treatment of Cushing’s syndrome is substantial. Through achieving target enrollment in the SONICS study, we are one step closer to better understanding the clinical value of Recorlev and potentially bringing a new therapeutic treatment option to this community,” said Matthew Pauls, president and chief executive officer of Strongbridge Biopharma.

The company expects to announce results of SONICS in the second quarter of 2018 and of LOGICS in the third quarter, according to the release.

For more information:

Clinicaltrials.gov/ct2/show/NCT01838551

From https://www.healio.com/endocrinology/adrenal/news/online/%7Bdddb8b5b-e4c8-412f-b4b8-82acde8f21a2%7D/drug-trial-begins-for-cushings-syndrome-therapy

Phase 3 SONICS Study Evaluating RECORLEV™ (levoketoconazole) in Endogenous Cushing’s Syndrome

DUBLIN, Ireland and TREVOSE, Pa., June 27, 2017 (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 it has met its enrollment target of 90 patients in the Phase 3 SONICS study evaluating the safety and efficacy of RECORLEV(levoketoconazole), a next-generation cortisol synthesis inhibitor, for the treatment of endogenous Cushing’s syndrome. Based upon strong interest in the SONICS study at the end of screening, a small number of additional potential study participants remain in screening and will be allowed to enroll, if qualified.

“We would like to sincerely thank our investigators, their clinical teams, and, most importantly, all of the patients from many countries around the globe for their continued dedication and participation in the SONICS study,” said Fredric Cohen, M.D., chief medical officer of Strongbridge Biopharma. “We currently still have patients in screening for SONICS due to the high level of interest and demand in the study.  Although we have reached target enrollment, we are pleased to extend the study for a brief period to accommodate those in screening who qualify. This will enable us to report top-line results in the second quarter of 2018,” Dr. Cohen added.

“The need for a safe and effective, next-generation cortisol synthesis inhibitor, such as RECORLEV, in the treatment of Cushing’s syndrome is substantial. Through achieving target enrollment in the SONICS study, we are one step closer to better understanding the clinical value of RECORLEV and potentially bringing a new therapeutic treatment option to this community,” said Matthew Pauls, president and chief executive officer of Strongbridge Biopharma. “Because we strongly believe in the potential of RECORLEV to become a best-in-class therapy, and as previously announced, we have strengthened our Phase 3 development plan to include LOGICS, a nine-week, placebo-controlled study, which will complement the long-term SONICS study. We anticipate availability of top-line data from the LOGICS study in the third quarter of 2018,” Pauls added.

SONICS and LOGICS are multinational Phase 3 studies designed to evaluate the safety and efficacy of RECORLEV when used to treat endogenous Cushing’s syndrome. SONICS is a single-arm, open-label study conducted in three treatment phases. Patients titrate to a therapeutic dose in the first phase and are maintained at the therapeutic dose for six months in the second phase, the end of which marks the primary efficacy time point. A six-month extended evaluation is included for long-term safety evaluations. LOGICS uses a placebo-controlled, double-blind, randomized-withdrawal design. Approximately 35 patients with Cushing’s syndrome will be randomized in LOGICS, of which approximately one-half will have previously completed SONICS. Together, the SONICS and LOGICS studies will include the participation of approximately 100 clinical research sites in over 20 countries in North America, Europe and the Middle East.

For more information on the SONICS study, please visit ClinicalTrials.gov and reference identifier: NCT01838551.

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. Cushing’s syndrome 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 first commercial product is KEVEYIS® (dichlorphenamide), the first and only FDA-approved treatment for hyperkalemic, hypokalemic, and related variants of Primary Periodic Paralysis. KEVEYIS has orphan drug exclusivity status in the U.S. through August 7, 2022. In addition to establishing this neuromuscular disease franchise, the Company has a clinical-stage pipeline of therapies for rare endocrine diseases. Strongbridge’s lead compounds include RECORLEV (levoketoconazole), a cortisol synthesis inhibitor currently being studied for the treatment of endogenous Cushing’s syndrome, and veldoreotide, a next-generation somatostatin analog being investigated for the treatment of acromegaly, with potential additional applications in Cushing’s syndrome and neuroendocrine tumors. Both RECORLEV and veldoreotide have received orphan designation from the U.S. Food and Drug Administration and the European Medicines Agency. For more information, visit www.strongbridgebio.com.

Forward-Looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties.  All statements, other than statements of historical facts, contained in this press release, are forward-looking statements. These statements relate to future events and involve known and unknown risks, including, without limitation, uncertainties regarding Strongbridge’s strategy, plans, anticipated investment, status and results of clinical trials and objectives of management for future operations. 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. 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.

Contacts:

Corporate and Media Relations
Elixir Health Public Relations
Lindsay Rocco
+1 862-596-1304
lrocco@elixirhealthpr.com

Investor Relations
U.S.:
The Trout Group
Marcy Nanus
+1 646-378-2927
mnanus@troutgroup.com

Europe:
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+47 21 04 62 19
strongbridgebio@firsthouse.no

USA
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Trevose, PA 19053
Tel. +1 610-254-9200
Fax. +1 215-355-7389

From http://www.globenewswire.com/news-release/2017/06/27/1029452/0/en/Strongbridge-Biopharma-plc-Completes-Target-Enrollment-of-90-Patients-in-the-Phase-3-SONICS-Study-Evaluating-RECORLEV-levoketoconazole-in-Endogenous-Cushing-s-Syndrome.html

Medical Therapies in Cushing’s Syndrome

Chapter

The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease

pp 165-179

Date: 03 December 2016

Medical Therapies in Cushing’s Syndrome

Abstract

Medical therapy has an important, albeit secondary, role in patients with Cushing’s syndrome. While medications are not currently used as definitive therapy of this condition, they can be very effective in controlling hypercortisolism in patients who fail surgery, those who are not surgical candidates, or those whose tumor location is unknown. Medical therapies can be particularly helpful to control hypercortisolism in patients with Cushing’s disease who underwent radiation therapy and are awaiting its salutary effects.

Currently available treatment options include several steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane, etomidate), which block one or several steps in cortisol synthesis in the adrenal glands, centrally acting agents (cabergoline, pasireotide), which decrease ACTH secretion, and glucocorticoid receptor antagonists, which are represented by a single agent (mifepristone). With the exception of pasireotide and mifepristone, available agents are used “off-label” to manage hypercortisolism. Several other medications are at various stages of development and may offer additional options for the management of this serious condition.

As more potential molecular targets become known and our understanding of the pathogenesis of Cushing’s syndrome improves, it is anticipated that novel, rationally designed medical therapies may emerge. Clinical trials are needed to further investigate the relative risks and benefits of currently available and novel medical therapies and examine the potential role of combination therapy in the management of Cushing’s syndrome.

Keywords

Cabergoline, Etomidate, Ketoconazole, Levoketoconazole, Metyrapone, Mifepristone, Mitotane, Osilodrostat, Pasireotide, Pituitary adenoma

Clinical Trial for levoketoconazole

This trial is testing the safety and effectiveness of a new investigational drug for the treatment of Cushing’s Syndrome. Under the supervision of qualified physicians, cortisol levels and symptoms of Cushing’s Syndrome will be closely followed along with any signs of side effects.

The investigational drug (levoketoconazole) is administered by mouth in the form of tablets.

This is a phase 3 trial.

There will be up to 90 participants worldwide in this trial. This page lists U.S. sites only.

Eligibility criteria

Participants must:

be at least 18 years old
have been diagnosed with endogenous Cushing’s Syndrome by a medical professional (endogenous means that it is caused by your body producing more cortisol than it needs, not caused by the use of steroid medications)
Participants must not:

have been treated with radiation for their endogenous Cushing’s syndrome in the past 4 years
be currently using weight loss medication
have a history of drug or alcohol abuse
have been diagnosed with uncontrolled hypertension, some forms of cancer, adrenal carcinoma, Hepatitis B / C, or HIV
Note: The study doctor will ultimately determine your eligibility
Study details

The length of this study and the number of study visits will vary from patient to patient. It has approximately 13 to 27 visits to the study site spread out over one to one and a half years. This study will enroll approximately 90 participants.

A placebo isn’t being used for this trial. All study participants will receive the investigational drug.

The sponsor of this trial is Cortendo AB.

The results of this trial are intended to be published. Individual patient information will not be included.

Reasonable travel expenses may be reimbursed.

This is a global study which will be conducted in multiple countries, with several sites in the US.

This information is intended for US audiences only.

Find out if you’re eligible here.

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