UPDATE: Shire's Vyvanse Approved in US for Children with ADHD
Shire plc (NASDAQ: SHPG), the global specialty biopharmaceutical company, today announced that the US Food and Drug Administration (FDA) approved the prescription medication Vyvanse^® (lisdexamfetamine dimesylate) Capsules, (CII) as a maintenance treatment in children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD). Vyvanse is currently approved as a maintenance treatment in adults with ADHD. With this new approval, Vyvanse becomes the only stimulant approved for maintenance treatment in children, adolescents, and adults (patients ages 6 and above) with ADHD.
The approval is based on results from a 32-week study: 26 weeks of open-label treatment with Vyvanse followed by a 6-week randomized withdrawal phase. The study was designed to evaluate the continued efficacy of Vyvanse in children and adolescents (aged 6 to 17 years). A significantly lower proportion of treatment failures occurred among Vyvanse patients (15.8%) compared to placebo (67.5%) at end point of the randomized withdrawal period, showing that significantly more patients treated with Vyvanse maintained ADHD symptom control compared with placebo.
Vyvanse is a Schedule II controlled substance. 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.
To evaluate the efficacy of Vyvanse for maintenance treatment in children and adolescents with ADHD, Shire elected to conduct a double-blind, placebo-controlled, randomized withdrawal clinical trial. In this design, patients who respond to a treatment are randomized to continue receiving that treatment or placebo. Using the proportion of patients experiencing symptom relapse as a primary outcome, this type of study in patients with ADHD can be used to demonstrate long-term efficacy in lieu of conducting a long-term, placebo-controlled, parallel-group study. The utility of this design is that the period of placebo exposure, with the potential for worsening of ADHD symptoms, is relatively short.
The double-blind, placebo-controlled, randomized withdrawal study was conducted in 276 children and adolescents aged 6 to 17 with ADHD. Of these patients, 236 participated in a preceding study and 40 directly enrolled. The study consisted of 4 phases:
o 4-week, open-label, dose-optimization phase in which patients received Vyvanse 30 mg/day, 50 mg/day, or 70 mg/day. Eligible subjects started on Vyvanse 30 mg/day and could be titrated in weekly increments of 20 mg until an optimal dose was reached (up to a maximum of 70 mg/day) o 20-week, open-label, maintenance phase o 2-week, open-label, fixed-dose phase in which patients were discontinued if they required further dose adjustments, experienced unacceptable tolerability, or had an Attention-Deficit/Hyperactivity Disorder Rating Scale, Version IV (ADHD-RS-IV) total score >22 or Clinical Global Impression Severity (CGI-S) score ≥3. Patients who maintained treatment response entered the randomized withdrawal phase. o 6-week, double-blind, randomized withdrawal phase in which patients either received ongoing treatment with the same dose of Vyvanse (N=78) or were switched to placebo (N=79).
The primary outcome measure was the proportion of patients who met criteria for relapse of ADHD symptoms (treatment failure) at end point during the double-blind, randomized withdrawal phase. The end point measurement was defined as the last post-randomization treatment week at which a valid ADHD-RS Total Score and CGI-S were observed. Treatment failure was defined as a ≥50% increase (worsening) in the ADHD-RS Total Score and a ≥2-point increase in the CGI-S score compared to scores at entry into the double-blind, randomized withdrawal phase. On the primary end point, significantly fewer patients met criteria for symptom relapse with Vyvanse (15.8%) versus placebo (67.5%) (P<.001).
During the 26-week open-label phase, 12 patients (4.3%) reported serious adverse events (SAEs), and 45 patients (16.3%) reported treatment-emergent adverse events (TEAEs) that resulted in Vyvanse discontinuation. During the randomized withdrawal phase, no SAEs were reported in the Vyvanse group, no patients in the Vyvanse group discontinued due to a TEAE, and 1 patient in the placebo group discontinued due to a TEAE. In addition, 39.7% (31/78) of patients receiving Vyvanse and 25.3% (20/79) on placebo reported TEAEs. The most common TEAEs (≥2%) reported in the Vyvanse treatment group during the randomized withdrawal phase included nasopharyngitis, headache, abdominal pain upper, oropharyngeal pain, decreased appetite, vomiting, weight decrease, abdominal pain, accidental overdose, aggression, cough, nausea and rhinitis.
Patients receiving Vyvanse demonstrated a moderate increase in mean pulse rate (~5 beats per minute) and blood pressure (~2 mm Hg systolic and diastolic blood pressure) between baseline and end point of the randomized withdrawal period. Patients treated with Vyvanse experienced a mean decrease in body weight of about 2 kg during the 26-week open-label period. Mean weight tended to increase in patients who switched to placebo during the randomized withdrawal phase. There were no deaths reported during the trial. The safety profile seen in this study was consistent with that of other studies of Vyvanse, and no new clinically relevant safety signals were associated with abrupt discontinuation of Vyvanse.
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