Viloxazine

Unassigned

New Medicines

Attention-deficit hyperactivity disorder (ADHD) in children aged 6 to 17 years

Information

New molecular entity
Supernus Pharmaceuticals
Supernus Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Not approved
Nov 20 · Supernus reports that it was on track to initiate commercial launch of SPN-812 in Jan 21, before it received a CRL from the FDA. The company plans to provide updates on the NDA status and expected launch timing once it has had further discussions with the FDA and has agreed on the path forward [7,8].
Nov 20 · US FDA issues a Complete Response Letter regarding the NDA for viloxazine hydrochloride for the treatment of paediatric patients with ADHD. The regulatory authority indicated that the application was not eligible for approval in the present form, citing the company ´s newly shifted in-house laboratory as the primary issue. The company has reported of its intention to hold discussions with the FDA so as to clarify that product release was not solely dependent on the said facility, as well as will discuss steps for a potential re-submission. No safety or efficacy issues were identified [6].
Dec 19 · Supernus plans to launch in the US in H2 20 [5].
Nov 19 · Supernus submits a new drug application (NDA) to the FDA for extended-release formulation of viloxazine hydrochloride for treatment of patients with ADHD. The NDA submission was supported by data from extensive development program consisting of four PIII trials that studied the paediatric patient population from the age of 6 to 17 years, two PII trials, several PI trials, long-term open label extension study, preclinical testing and drug manufacturing data [5].
Jun 19 · Supernus markets their products through their own sales force in the US and seek strategic collaborations with other pharmaceutical companies to commercialise products outside of the U.S. via license agreements. No plans currently announced for EU development [3].
Feb 19 · Supernus expects to submit a New Drug Application (NDA) for SPN-812 in H2 19, and to launch it, pending U.S. Food and Drug Administration (FDA) approval, in H2 20 [3].

Category

Norepinephrine reuptake inhibitor with selective serotonin modulation activity
The prevalence of ADHD is estimated to be around 2.4% of children in the UK, more common in boys [2].
Attention-deficit hyperactivity disorder (ADHD) in children aged 6 to 17 years
Oral

Trial or other data

Nov 20 · In the phase III P304 trial, SPN 812 (400 mg) exhibited statistical significance compared with placebo in the primary endpoint. At week 7, treatment with SPN 812 (400 mg) showed an -18.3 LS mean change from baseline (p=0.0082) versus LS mean change of-13.2 from baseline for placebo. Also, patients receiving SPN 812 (600 mg) had LS mean change of -16.7 (p=0.0712) from baseline in the primary endpoint. At week 7, in the intent-to-treat (ITT) population, the data based on the Mixed Model Repeated Measures (MMRM) analysis was similar to the results from the sensitivity analyses using Analysis of Covariance (ANCOVA) (400 mg, p=0.0191; 600 mg, p=0.1002). At the 400 mg dose, SPN 812 demonstrated statistically significant onset of action from week 2 (p=0.0063), to the end of study at week 7 (p=0.0082). At 600 mg dose, SPN 812 demonstrated statistically significant difference from placebo in the primary endpoint during the last week of titration (week 2 dosed at 400 mg, p=0.0456) and the first week of maintenance (week 3 dosed at 600 mg, p=0.0238). SPN 812 at the dosage of 400 mg reached statistical significance compared with the placebo on the hyperactivity/impulsivity (p=0.0484) and inattention subscales (p=0.0042) of the ADHD-RS-5 scale. When compared with the placebo, SPN 812 (400 mg) met the Clinical Global Impression-Improvement secondary endpoint (p=0.0051). However, SPN 812 at 600 mg dose was not statistically significant [6].
Mar 19 · PIII P304 trial that evaluated the efficacy and safety of high doses of extended-release formulation of viloxazine hydrochloride in adolescents with ADHD completes (P304; NCT03247556). The randomised, open-label, parallel, three-arm, placebo-controlled trial was initiated in Oct 17 and enrolled 297 patients, aged 12 years to 17 years, in the US [4].
Feb 19 · During Dec 18, Supernus announced positive topline results from the two paediatric PIII trials (P301; NCT03247530 and P303; NCT03247543) and from the first adolescent PIII trial (P302; NCT03247517). All three trials met the primary endpoint with robust statistical significance. Topline data from the second and final adolescent PIII trial (P304) are expected by end Q1 19 [3].
Dec 18 · In PIII trial SPN-812 200 mg and 400 mg reached statistical significance compared to placebo on the hyperactivity/impulsivity and inattention subscales of the ADHD-RS-5 scale with p-values ranging from 0.0005 to 0.0424 [1].