Aerie Pharmaceuticals’ hypothesis was correct, putting it back in the glaucoma game. Evaluating the efficacy of Rhopressa only in those patients with intraocular pressure (IOP) of 20-25mmHg proved the right plan for showing that the eye drop is the equal of timolol.
Shares surged 70% to $30.52 in early trading today, restoring nearly all of the market valuation the California-based group lost when an earlier phase III trial missed a non-inferiority endpoint. Having the FDA on-side in its revision of the pivotal programme should allow an NDA filing to proceed next year, allaying fears that the initial failure at best would lead to a delay and at worst endanger Aerie’s entire late-stage pipeline.
Find the right patients
The miss in the earlier Rocket-1 trial was attributed to a subgroup of patients who had IOP between 25mmHg and 27mgHg. After consulting with a glaucoma specialist, Stifel analyst Annabel Samimy suggested that the cause might have been fibrosis in these patients that makes Rhopressa’s main mechanism of action, rho kinase inhibition, ineffective.
This subgroup analysis was apparently persuasive enough for the FDA to allow a revision in the analysis plan of Rocket-2 to make the sub-25 group the primary endpoint, with a secondary endpoint covering the patients up to 27 (FDA “feedback” buys Aerie some breathing space, June 17, 2015). On this Rhopressa was a winner, Aerie said, showing statistical non-inferiority to twice-daily timolol with both a once and twice-daily dose at days 15, 24, and 90 in the sub-25s, but missing when the patients up to 27mmHg were included.
Both doses had a numerically higher early termination rate than did timolol, with 40% in the twice-daily group dropping out.
Rhopressa has one other phase III trial under way, a safety study in Canada called Rocket-3. Aerie said it would initiate a fourth study later this month, but data accumulated so far should be sufficient for the group to submit an NDA in mid-2016.
Forecasts for Rhopressa should rise in the near future, as sellside analysts significantly trimmed them in the wake of the Rocket-1 failure. EvaluatePharma’s consensus stands at $61m in 2020, down from $151m in May 2015.
Rho-ing Aerie’s boat
Perhaps more significant for Aerie is the fact that rho kinase inhibition still appears to be a viable approach to relieving IOP in glaucoma. This target allows for fluid to drain through the trabecular meshwork; Rhopressa also contains a norepinephrine transporter, which modulates production of intraocular fluid.
Aerie’s next pipeline candidate is Roclatan, a combination of Rhopressa with the standard-of-care treatment latanoprost – its first phase III study, Mercury 1, is set to begin by the end of this month. Another failure for Rhopressa would have cast significant doubt on the promise of that project.
These findings almost surely will have piqued the interest of partners or buyers. Should detailed data add further weight to these topline figures, it might not be long before Novartis or Allergan come calling.