Supernus Announces Positive Results from SPN-812 Study for ADHD

Supernus Pharmaceuticals has announced positive topline results from a Phase III study of SPN-812 in adults (P306) for the treatment of attention deficit hyperactivity disorder (ADHD).

At a daily dose of up to 600mg, the trial met the primary endpoint with robust statistical significance (p=0.0040) compared to placebo in improving the symptoms of ADHD from baseline to end of study as measured by ADHD Investigator Symptom Rating Scale (AISRS). In addition to meeting the primary efficacy endpoint, the Phase III study met the key secondary efficacy endpoint with statistical significance (p=0.0023) in the change from baseline of the Clinical Global Impression – Severity of Illness (CGI-S) Scale at week 6. The active dose was well tolerated.

SPN-812 is under review by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD in pediatric patients 6 to 17 years of age. As announced in November, 2020, the FDA issued a Complete Response Letter (CRL) regarding the New Drug Application (NDA) for SPN-812 for the treatment of ADHD in pediatric patients to indicate that the review cycle for the application was complete and that the application is not ready for approval in its present form. The Company will be meeting with the FDA in January 2021 to discuss the CRL. Assuming approval for pediatrics, the Company plans to submit a supplemental NDA (sNDA) to the FDA for SPN-812 in adults in the second half of 2021.

“These compelling data in adults will be important for our planned sNDA submission to make this treatment option available, if approved by the FDA, to the adult ADHD patient population, which represents approximately half of the total ADHD market in the U.S.,” said Jack Khattar, President and Chief Executive Officer of Supernus Pharmaceuticals. “We now have positive Phase III data proving the efficacy and safety of SPN-812 in a broad range of ADHD patient populations; children 6-11 years old, adolescents 12-17 years old, and adults.”

The study was a randomized, double-blind, placebo controlled, multicenter, parallel group clinical trial in adult patients diagnosed with ADHD. The study had a two-arm flexible dose design where treatment was administered orally once a day over six weeks, including the titration phase up to a total daily dose of 600mg SPN-812 or matched placebo.

A total of 374 adult patients were randomized across placebo and a daily dose of SPN-812 starting with 200mg with flexible dose administration up to 600mg. The primary objective was to assess the effect of SPN-812 in reducing the symptoms of ADHD. The primary outcome measure was the change from baseline to the end of the study in the AISRS. Safety and tolerability of SPN-812 were assessed by the monitoring of adverse events (AEs), clinical laboratory tests, vital signs, ECGs, suicidality and physical examinations. Patients who completed the study were offered the opportunity to continue into an ongoing open-label safety extension study.

At the end of the study, SPN-812 reached statistical significance compared to placebo in the primary endpoint. Patients receiving SPN-812 had a -15.5 point change from baseline in the primary endpoint compared to -11.7 for placebo at week 6 (p=0.0040).

This primary result, based on a Mixed Model Repeated Measures (MMRM) analysis using the Full Analysis Set (FAS) population, was confirmed by sensitivity analysis with a p-value of 0.0085.

The study demonstrated fast onset of action, reaching statistical significance as early as week 2 with a p-value of 0.0397, and maintaining statistical significance through the end of the trial at week 6.

Similar to the previously reported studies in pediatric patients 6 to 17 years of age, at the end of the P306 study, SPN-812 reached statistical significance compared to placebo on the hyperactivity/impulsivity and inattention subscales of the AISRS with p-values of 0.0380 and 0.0015, respectively.

In addition, SPN-812 met the CGI-S secondary endpoint with a p-value of 0.0023 compared to placebo at week 6 and showed significant improvement as early as week 2 with a p-value of 0.0203.

SPN-812 is a novel non-stimulant for the treatment of ADHD. Based on data generated to date, the Company believes SPN-812 could be a well-differentiated ADHD treatment due to its different pharmacological and pharmacokinetic profile. The active ingredient in SPN-812, viloxazine hydrochloride, has an extensive safety record in Europe, where it was previously marketed for many years as an antidepressant.