Supernus’ stocks down once more, despite positive phase 3 ADHD data for SPN-812

Supernus Pharmaceuticals unveiled topline results from two phase 3 studies of children with attention deficit hyperactivity disorder but failed to wow investors worried about how its nonstimulant treatment would take on already-established generics.

The company’s SPN-812, a norepinephrine reuptake inhibitor that modulates serotonin activity, showed early efficacy across a rubric of hyperactivity, impulsivity and inattention scales. Its active ingredient, viloxazine HCl, was previously sold in Europe as an antidepressant. The two studies randomized nearly 800 children ages 6 to 11 to placebo or 100-mg, 200-mg or 400-mg daily doses.

Both trials demonstrated statistical significance, with the lower doses of 100 mg and 200 mg showing onsets of activity as early as the first week in one study, according to Supernus. The second study, evaluating 200-mg and 400-mg doses, reached significance in the fifth week of the seven-week trial but showed similar treatment effects early on as well.

The Rockville, Maryland-based company said it plans to submit an NDA in the second half of next year—following the expected release of topline data from two additional phase 3 trials in adolescents with ADHD, including from one study by the end of the month—with a potential commercial launch slated for the second half of 2020.

“We believe these data from the two pivotal phase 3 studies, which are consistent with the phase 2b data, demonstrate that SPN-812 is a well-differentiated novel non-stimulant treatment option for many children with ADHD,” Jack Khattar, Supernus’ president and CEO, said in a statement.

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All doses were well-tolerated, the company said, with the trials showing discontinuation rates of 2.2% to 4.8%. Patients who completed the study were offered to continue in an ongoing, open-label phase.

The company’s main competition would come from generic versions of Eli Lilly’s Strattera (atomoxetine) nonstimulant treatment, which went off patent in May 2017.

Following the release of the latest phase 3 data, Supernus’ stocks dropped as much as 13% in premarket trading, with SPN-812’s numbers failing to knock Strattera out of the park. Supernus drew a similar reaction to its phase 2 data in 2016, which hit its primary endpoints, but shares still ticked down as investors sold on the news.

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With SPN-812’s average effect sizes being about the same as or smaller than Strattera’s, the company pointed to the early onsets as the main differentiator, including in the first week with the titration dose of 100 mg.

“We don’t need to match the effect sizes of stimulants or even the ones that Strattera got,” Khattar said on a conference call with investors, pointing to variabilities in previous studies for both drugs. However, Strattera has also demonstrated early onsets in previous studies.

But based on its confidence in the phase 3 data, Supernus projects that SPN-812 could claim a market share in the range of 3% to 5%, numbers Khattar described as “fairly conservative.” In addition, the company expects the eventual label to not carry warnings for liver or cardiovascular toxicity, compared to Strattera, he said.

At the end of the day, “physicians treat with the clinical efficacy that they see,” Khattar said, adding that doctors are looking for new treatments that aren’t reformulations of amphetamines or methylphenidates. “And parents don’t want to wait until six weeks into the school year to see if this thing works or not.”