Welcome to your weekly digest of approaching regulatory and clinical readouts. Aerie (NASDAQ:AERI) will be hoping that its glaucoma project Roclatan repeats the performance in its earlier positive phase III trial when data from a new study are released shortly; since safety concerns cloud its other glaucoma asset, Rhopressa, Aerie needs a win here.
And results from AbbVie's (NYSE:ABBV) phase III studies of ABT-494 in rheumatoid arthritis are due mid-year. This Jak-1 inhibitor is a valuable asset for the company, and while the recent rejection of Lilly's (NYSE:LLY) Olumiant is a plus for competing assets this could lead to tougher regulatory inspection.
Second time's the charm
Last September, in a glaucoma trial called Mercury 1, Roclatan significantly reduced intraocular pressure compared with either Rhopressa or latanoprost, both constituents of Roclatan, measured after two weeks, six weeks and three months. Aerie shares rocketed 45%, putting them on a level last seen before Rhopressa failed its phase III back in April 2015 (Aerie parties like it's 2015 with Roclatan win, September 15, 2016).
However, there are reasons to be cautious. In Mercury 1 half of Roclatan patients reported conjunctival hyperaemia, compared with 14% of latanoprost patients, and 10% reported conjunctival hemorrhage, while less than 1% of those taking latanoprost did.
The second trial, Mercury 2, has the same primary endpoint - intraocular pressure at three months - and safety data will likely be watched closely when results are released in the second quarter. The company expects to file by the end of the year or in early 2018. Roclatan sales are forecast to hit $453m by 2022, according to sellside consensus compiled by EvaluatePharma.
Aerie has been unable to allay safety concerns with Rhopressa, with a recent cut of safety data showing higher adverse events with the treatment. The FDA accepted its filing last week, but fears remain over how payers would view the drug and how restrictive the label might be if it is approved.
12-month safety data from Mercury 1 are expected in the third quarter, while Mercury 3 will start in the second quarter and will be used to support European approval. It is expected to compare Roclatan with Allergan's (NYSE:AGN) fixed-dose combination Ganfort.
ABT-494, which contains the active ingredient upadacitinib tartrate, is in two phase III trials called Select-Beyond and Select-Next, due to report by the middle of the year. Select-Next has enrolled 600 RA patients who have had inadequate response to conventional synthetic DMARDs (csDMARDs). Select-Beyond tests the project in 450 RA patients on stable csDMARDs who have had an inadequate response or are intolerant to biological DMARDs.
Both trials are investigating two doses of ABT-494 versus placebo. The primary endpoints are the proportion of patients achieving ACR20 response and low disease activity at 12 weeks.
Altogether five phase III trials of ABT-494 are under way in RA, including Select-Compare, in which it will be compared with Humira, and which has a primary completion date of August.
Lilly's Jak-1/2 inhibitor Olumiant got a surprise US rejection last week, with the FDA citing dosing and safety data, just two months after European officials approved it. This could put launch of ABT-494 and Gilead (NASDAQ:GILD) and Galapagos' (NASDAQ:GLPG) (OTC:GLPGF) (OTCPK:GLPYY) filgotinib, also a Jak-1, on a similar timeline to Olumiant, which is now seen being launched in 2020 as additional clinical data are needed. Rival Jaks could now also face heightened FDA scrutiny, though they have the advantage of being forewarned (Olumiant setback opens the door to rivals, April 18, 2017).
As novel RA entrants go ABT-494 has substantial forecasts; sales are expected to reach $1.2bn by 2022, according to EvaluatePharma. Its NPV of $6.3bn - 6% of AbbVie's market cap - makes it AbbVie's most valuable R&D project, an important asset as the threat from Humira biosimilars looms.