Aurinia Pharmaceuticals has been given a glimmer of hope to push on with voclosporin ophthalmic solution in dry eye disease, but phase II data released today are far from conclusive about the project's promise.
The data contained two surprises. One was that voclosporin was not more tolerable than Allergan's top-selling eyedrop Restasis, meaning that the trial missed its primary endpoint. Secondly, Aurinia's candidate showed signs of superior efficacy to Restasis. Allergan’s loss of market exclusivity means that the dry eye market will be tough to break into, and the mark to beat might not be set by Restasis, but rather by Shire’s Xiidra.
Investors appeared to be confused about the meaning of the data, with a sell-off and recovery pre-market, only to sell again once the markets opened. Aurinia shares were off 2% in afternoon trading.
Aurinia had hoped that voclosporin eyedrops would score lower than Restasis on drop discomfort scores one minute after treatment on the first day of the trial. The study revealed that the two were statistically similar, however, with Restasis looking numerically lower.
Aurinia executives were quick to stress that the discomfort scores for both were low. Tolerability is one of the limitations for Restasis, so voclosporin would have scored a big win if it had differentiated itself here.
On the other hand, the efficacy findings were encouraging. Among patients taking voclosporin, 42.9% saw an increase of 10mm or more in their Schirmer tear test score in their worst eye, significantly greater than the 18.4% of patients taking Restasis.
This was the endpoint the FDA relied on when approving Restasis in 2002: 15% of patients in the registrational trials saw an increase of 10mm or more.
Meanwhile, Shire's Xiidra won approval on mean change in eye dryness scores and fluorescein corneal staining scores over 84 days. Only on the latter endpoint can Xiidra be compared with voclosporin – at 84 days Xiidra saw a reduction of 0.17 to 0.73, while voclosporin at four weeks saw a reduction of 2.2.
Aurinia’s trial was smaller and shorter than those used for approval of Restasis or Xiidra, which exceeded 1,000 patients in each case, so the efficacy finding with voclosporin would need to be repeated in pivotal studies of a similar size.
Executives of Canada-based Aurinia said that in retrospect they should have chosen efficacy as the primary endpoint of their phase II trial. Nevertheless, the efficacy findings have given the company the confidence to move the programme forward “aggressively” – although the execs would not set timelines or even state if phase III would be the next step.
Leerink analyst Joseph Schwartz believes that a second phase II trial is in the offing because Aurinia might want to test the hypothesis that a lower dose could improve tolerability without giving up the efficacy benefit.
In the meantime, the company downplayed any suggestion that it might seek a partner in the near term, saying it wanted to research the project further and improve its value. This could make investors nervous, as it could distract Aurinia’s R&D team from a bigger catalyst: readout of the phase III Aurora trial in lupus nephritis, where it is hoped that a voclosporin pill can reduce renal symptoms. Data are expected by the end of the year.
Voclosporin already had mixed results in that setting; the earlier Aura-LV trial in lupus was troubled by an inconsistent dose response and an imbalance in deaths (Aurinia suffers a headache with Aura, August 15, 2016). In spite of that setback, the sellside expects voclosporin sales of $649m in 2024, according to EvaluatePharma’s consensus.
Lupus has been a problematic disorder for drug developers. Glaxosmithkline’s Benlysta was the first agent in 50 years to achieve approval in 2011, and nothing has emerged since. It might be just as well that Aurinia has the dry eye indication as a second shot on goal, even if investors are cool to it.