Auspex ends the year on a high note
Results from Auspex Pharmaceuticals’ SD-809 in Huntington’s chorea could not look much better. The very least the company had to demonstrate was that its modified version of Xenazine, SD-809, is better tolerated than Xenazine itself: not only does this appear to be the case, but ‘809’s effectiveness in calming the uncontrolled movements associated with the degenerative neurological disease also looks superior.
Auspex did not test the two drugs side by side so these conclusions are drawn with the usual caveats of comparing different studies. However, the data certainly look strong enough for approval and SD-809 will be sent to the FDA next year for review. The near doubling of the company’s market value today suggests investors are betting on a green light, and further clinical wins for the drug.
SD-809 is a deuterated form of Xenazine – the molecule has been engineered to substitute hydrogen with deuterium – a process designed to improve the pharmacokinetics of the original molecule.
With Xenazine there is certainly room for improvement. The drug carries black box warnings for depression and suicidal thoughts and behaviour, can only be dosed up to 50mg a day before patients must be genotyped for the drug metabolizing enzyme CYP2D6, and in trials was associated with various CNS concerns as well as QTc prolongation.
On efficacy, Xenazine was approved on a significant 3.5 unit improvement on the total chorea score over placebo. However, the study missed various secondary endpoints and actually showed a numerical decrement for Xenazine patients on one functional measure and a cognitive test.
Despite all this it won US approval in 2008 – the FDA took more than three years of convincing and insists on a stringent REMS programme – and it remains the only regulator-sanctioned drug for Huntington’s. Sold by Lundbeck in most territories, sales are forecast to reach $292m this year according to EvaluatePharma consensus, despite only being used by an estimated 10% of moderate-to-severe patients with chorea.
Auspex also used the change in chorea score over placebo for the primary endpoint in its registration trial of SD-809, called First-HD. The drug generated a significant 2.5 unit improvement over placebo, equal to 21 percentage points, a finding the company describes as highly clinically significant.
Patients’ total motor score, which captures movement measures beyond chorea, was also significantly improved – an endpoint that Xenazine failed to hit, Auspex says. Secondary endpoints, including patient and physician impression of change and quality of life scores, were also achieved; the Berg Balance test was not improved, although a trend favouring SD-809 was seen.
With Xenazine due to lose patent protection in August 2015, however, an improved tolerability profile was always going to be the crucial factor to give SD-809 a chance in the market.
Data on adverse events did not disappoint. Closely watched psychiatric measures and nervous system disorders showed few notable imbalances between the arms, and more than 90% of patients chose to roll over into a longer term safety study.
Auspex also released results from a switching study, that showed patients could safety move to SD-809 overnight and maintain control of their chorea.
Setting the stage
Auspex shares soared to $49 in early trade, valuing the company at $1.3bn; the stock floated at $12 in February.
Investor enthusiasm also reflects heightened hopes for bigger and more lucrative indications in which the drug is also being tested: phase III data from the first of two studies in tardive dyskinesia will be released mid-2015, as well as phase I data in Tourette syndrome.
Of course the company still has the FDA to convince; although it is pursuing an abbreviated 505(b)(2) pathway the known issues with Xenazine will prompt close scrutiny. And then conversations with payers must be held –with Xenazine generics likely to be available by then a premium price will surely be impossible.
In the meantime, Neurocrine is due to release pivotal data on its competing novel VMAT2 inhibitor, NBI-98854, in tardive dyskinesia towards the end of 2015.
So while the path forward appears to have cleared for SD-809, there is still some way to travel.
|Arc-HD (switch study)||NCT01897896|
|NBI-98854 TD study||NCT02274558|