Phase III trial of SHP 465 (triple-bead mixed amphetamine salts) in ADHD demonstrates efficacy and should lead to resubmission with FDA- Shire

Shire has announced positive topline results from a four-week Phase III, randomized, double-blind, multi-center, placebo-controlled, dose-optimization, safety and efficacy study, SHP465-305, with SHP 465 (triple-bead mixed amphetamine salts) in children and adolescents aged 6-17 years with Attention-Deficit/Hyperactivity Disorder (ADHD). The primary efficacy analysis of study 305 demonstrated that SHP465, administered as a daily morning dose, was superior to placebo on the change from baseline in ADHD-RS-IV (ADHD rating scale) total score, with a Least Squares (LS) mean difference from placebo at Week 4 of -9.9, suggesting a significant improvement in ADHD symptoms.

SHP465 was also superior to placebo in the key secondary efficacy analysis on the clinical global impression improvement scale (CGI-I), with an LS mean difference from placebo at Week 4 of -0.8, indicating a significantly higher proportion of patients were rated improved on the CGI-I rating scale. The CGI-I is a standardized assessment tool that allows clinicians to rate the severity of ADHD illness, change over time and efficacy of medication. Treatment-emergent adverse events of at least 5% for SHP 465-305 were decreased appetite, headache, insomnia, irritability, nausea, weight decrease and dizziness. Adverse events were generally mild to moderate in severity and similar to those observed in previous SHP465 studies and with other amphetamine compounds. The completion of SHP465-305 addresses an FDA requirement to evaluate the safety and efficacy of SHP465 in children and adolescents prior to filing a Class 2 resubmission of the medicine for FDA approval.

Comment: Pending FDA approval, Shire anticipates launching the medicine in the second half of 2017. This update follows Shire’s announcement on October 9, 2014, that it was engaging the FDA to determine the parameters of clinical data requirements in order to submit the Class 2 resubmission.