Shire plc (LSE: SHP, NASDAQ: SHPG) announces top-line results from two pivotal Phase 3 investigational studies evaluating the efficacy and safety of Vyvanse® (lisdexamfetamine dimesylate) Capsules (CII) versus placebo as an adjunctive treatment for major depressive disorder (MDD) in adults who inadequately responded to antidepressant monotherapy with a SSRI or SNRI. Vyvanse did not meet the primary efficacy endpoint versus placebo for either study. The safety profile for Vyvanse in these two studies appears to be generally consistent with the known profile established in studies in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Based on these clinical trial results, Shire will no longer pursue this clinical development program.
“While this news in major depressive disorder is disappointing for patients and Shire, we will later in the year be filing with the FDA for a new indication for Vyvanse in Binge Eating Disorder in adults, and Vyvanse is an effective and leading treatment for ADHD,” said Flemming Ornskov, M.D., Shire’s Chief Executive Officer. “We remain committed to serving patients with ADHD and will invest in solutions to meet their treatment needs accordingly. Shire’s portfolio of treatments in rare diseases is also growing, strengthened recently with the acquisition of ViroPharma. Rare Diseases is an area of great unmet patient need and it’s where we will increasingly focus our strategic development and investment."
Vyvanse is a prescription medicine currently only approved for the treatment of ADHD in the United States, Canada, Australia, several European countries (trade name: Elvanse®/Tyvense®) and Brazil (trade name: Venvanse™). Vyvanse should only be used in accordance with locally approved prescribing information.
CNS stimulants (amphetamines and methylphenidate-containing products) have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy.
ABOUT THE MDD STUDIES
Each of the two identically designed Phase 3, multi-center, randomized, double-blind, parallel-group, placebo-controlled, dose-optimized studies was designed to assess the efficacy, safety, and tolerability of Vyvanse in patients aged 18 to 65 who met DSM-IV-TR® criteria for a diagnosis of MDD. The first study randomized (404 adults), and the second study randomized (426 adults). The primary efficacy endpoint for the studies was defined as the change from augmentation baseline (Week 8) to Week 16 in Montgomery-Çºsberg Depression Rating Scale (MADRS) total score. Vyvanse did not meet the primary efficacy endpoint versus placebo for either study (p=0.883, p=0.583). In the first study, subjects experienced a mean reduction of 6.1 in MADRS total score for Vyvanse compared with 6.3 for placebo. Augmentation baseline MADRS scores for Vyvanse and placebo groups were 25.4 and 25.2 respectively. In the second study, subjects experienced a mean reduction of 7.3 in MADRS total score for Vyvanse compared with 6.8 for placebo. Augmentation baseline MADRS scores for Vyvanse and placebo groups were 26.0 and 25.7 respectively.
Safety and tolerability of Vyvanse were evaluated based on treatment-emergent adverse events (TEAEs), vital signs, weight, clinical laboratory results, and electrocardiogram (ECG) results.
In study SPD489-322, 3 patients treated with Vyvanse and 5 patients treated with placebo experienced serious adverse events (SAEs). Eight (8) patients on Vyvanse and 7 patients on placebo had TEAEs that led to study discontinuation. The most commonly reported (>5% of subjects) TEAEs in subjects taking Vyvanse included insomnia, dry mouth, decreased appetite, headache, nausea, nasopharyngitis, and dizziness.
In study SPD489-323 1 patient treated with Vyvanse and 1 patient treated with placebo experienced serious adverse events (SAE). Two (2) patients on Vyvanse and 1 patient on placebo had treatment-emergent adverse events (TEAEs) that led to study discontinuation. The most commonly reported (>5% of subjects) TEAEs in subjects taking Vyvanse included headache, dry mouth, nasopharyngitis, decreased appetite, insomnia, hyperhidrosis and restlessness.
Further evaluation of the safety information related to vital signs, ECG, and clinical laboratory results and other safety assessments is currently under way.
The 16-week studies consisted of an 8-week single blind lead-in phase with an antidepressant (selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI)), and an 8-week double-blind adjunctive treatment phase. Subjects who demonstrated an inadequate response to the antidepressant treatment at Week 8, defined in the study protocol as having a MADRS total score ≥ 18 and a <50% reduction in the MADRS total score from the lead-in baseline (Week 0), entered the adjunctive treatment phase and were randomized to Vyvanse or placebo treatment groups. During the double blind period, Vyvanse dosing was optimized over the range of 20 to 70 mg, based on clinical criteria.
Subjects were excluded if they had inadequate response to a treatment regimen with two or more approved single antidepressant agents in their current episode of MDD, a lifetime history of treatment resistant depression, or were considered a suicide risk; certain medical comorbidities (cardiovascular risk, moderate to severe hypertension); a history of ADHD diagnosis, symptoms or treatment with ADHD medication; and/or a lifetime history of amphetamine, cocaine, or other stimulant abuse and/or dependence.
ABOUT Vyvanse® (lisdexamfetamine dimesylate)
Vyvanse is indicated for the treatment of ADHD in patients ages 6 and above. Efficacy was established in short-term controlled studies in children aged 6 to 17 and in adults. Vyvanse is also approved as a maintenance treatment for patients ages 6 and above with ADHD based on one maintenance study in patients aged 6 to 17 and one maintenance study in adults.
IMPORTANT SAFETY INFORMATION
WARNING: ABUSE AND DEPENDENCE
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For further information please contact:
+1 781 482 0999
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NOTES TO EDITORS
Shire enables people with life-altering conditions to lead better lives.
Our strategy is to focus on developing and marketing innovative specialty medicines to meet significant unmet patient needs.
We provide treatments in Neuroscience, Rare Diseases, Gastrointestinal and Internal Medicine and we are developing treatments for symptomatic conditions treated by specialist physicians in other targeted therapeutic areas.
The Vyvanse®, Elvanse®, Tyvense®, and Venvanse™ marks used in this release are trademarks of Shire plc or companies within the Shire group.
FORWARD - LOOKING STATEMENTS - "SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included in this announcement that are not historical facts are forward-looking statements. Forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, that:
and other risks and uncertainties detailed from time to time in Shire’s filings with the U.S. Securities and Exchange Commission, including its most recent Annual Report on Form 10-K.
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