Investors had already been worried about the ability of Supernus’s non-stimulant ADHD contender SPN-812 to muscle in on a crowded market. And the project’s cause will not have been helped by it flunking its most recent phase III trial.
Today’s failure came after success in three previous pivotal studies, so Supernus might still have an approvable drug. But competing against generic versions of Lilly's similarly acting product, Strattera, now looks like an even tougher task.
The study reported today, called P304, evaluated SPN-812 dosed at 400mg or 600mg daily in adolescents with ADHD. The primary endpoint was change from baseline on ADHD-RS-5 scale with SPN-812 versus placebo.
The lower dose dose did numerically better on this measure than the higher one; indeed, the latter did not hit statistical significance. Unfortunately for Supernus, the statistical plan called for the 600mg dose to be evaluated first in the hierarchy, meaning that the p value for the 400mg, 0.0082, was only nominally significant.
The company’s press released claimed that the lower dose had met significance, but Supernus’s chief executive, Jack Khattar, admitted on a conference call today that the 400mg data from study P304 could only be considered supportive.
Still, Supernus believes that it has enough to file an NDA for SPN-812 – presumably not including the 600mg dose – which it plans to do in the second half of 2019.
Three other phase III trials, two in children and one in adolescents, hit their primary endpoints at all doses studied; none included a 600mg cohort.
|Reaching a plateau? Phase III data with SPN-812|
|Study||Setting||Change in ADHD rating scale-5||Trial ID|
|P301||Low dose in children||-10.9||-16.6||-17.7||NCT03247530|
|P303||High dose in children||-11.7||-17.6||-17.5||NCT03247543|
|P302||Low dose in adolescents||-11.4||-16.0||-16.5||NCT03247517|
|P304||High dose in adolescents||-13.2||-18.3*||-16.7**||NCT03247556|
|Note: *nominally positive, but statistically not significant; **did not meet statistical significance vs placebo; all other trials met significance vs placebo. Source: company press releases.|
Mr Khattar said today’s failure might be explained by a dose-plateauing effect with SPN-812, a serotonin and norepinephrine modulating agent. He added that the placebo response had been higher in this trial than in the others, which yielded data in December.
But even before today’s data investors had been sceptical of SPN-812’s chances on the market. SPN-812 has not shown better efficacy than Lilly’s Strattera, a norepinephrine reuptake inhibitor, which lost patent protection in 2017.
SPN-812 looks to take effect more rapidly than Strattera, and might also have a better safety profile. Strattera has warnings on its label for liver injury and serious cardiovascular events, something that SPN-812 has so far managed to avoid.
This might not be enough to tempt doctors away from prescribing cheaper alternatives, however. And SPN-812 is unlikely to escape a warning for suicidality, which also features on Strattera’s label. Supernus’s project also has a higher rate of somnolence, something that was seen again in study P304.
If Supernus hopes to take market share from stimulants used for ADHD, such as Ritalin, this could also be a non-starter: despite their side effects, the stimulants are seen as more effective, and non-stimulants only make up around 15% of the market, according to Stifel analysts. Supernus also plans to start trials of SPN-812 in adults with ADHD later this year.
The company’s stock barely moved today, after plunging on the previous pivotal wins. The latest data might not have changed the picture much, but the picture already looked gloomy.