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Tuesday, April 2, 2019

Does improved safety boost Allergan’s case for wet AMD challenge to Lucentis?

Allergan has chalked up some flattering safety data for abicipar as it refines the eye drug’s manufacturing processes in preparation of an impending BLA filing. But whether or how much that matters is still up for debate.
In an open-label, single-arm study, investigators reported that the incidence of intraocular inflammation was 8.9% — lower than the rate observed in prior Phase III studies, which hovered around 15%. The MAPLE trial recruited 123 age-related neovascular macular degeneration (or wet AMD) patients and administered the injection five times over 28 weeks.

“The results of this open-label study enabled us to assess improvements to the manufacturing process for abicipar. The safety profile demonstrated in MAPLE gives us confidence to proceed and scale up manufacturing,” said David Nicholson, chief research and development officer. “We plan to submit the abicipar BLA and continue to pursue manufacturing process improvements as we develop larger scale studies in additional disease states, such as diabetic macular edema.”
Any little improvement could be crucial as Allergan and its allies at Molecular Partners go up against the entrenched market leaders, Regeneron’s Eylea and Novartis’ Lucentis, both approved for multiple indications other than wet AMD, which is far less common but much more severe than dry AMD. And the two giants are each advancing follow-on efforts of their own.
The new inflammation rates, though, might still do little to change investors’ skeptical views on the commercial prospect, said Umer Raffat of Evercore ISI.
Raffat notes that severe inflammation registered at 1.6% in the MAPLE trial, compared to 3.2% to 3.7% observed in previous Phase III studies.
AGN feels strongly that it’s really just the severe inflammation that matters … and that it’s now at a well controlled rate (<2%) … and that mild inflammation is asymptomatic.
If we agree with AGN’s logic, there is an impt piece of data that hasn’t been disclosed about MAPLE: the rate of moderate inflammation. (we know mild+mod+severe = 8.9% … and severe is 1.6% … but what is moderate? if we go by Ph 3 results, moderate could be half of this 8.9% … but unclear if that actually happened in MAPLE also).
To put it bluntly: “It will be a ‘show-me’ story at launch.”
Analysts for SVB Leerink was even more doubtful, noting:
Reported incidence of intraocular inflammation (IOI) was 8.9% in the MAPLE study, which was lower than prior Phase 3 studies (>15% after 1 year of treatment), but still significantly higher than the rate observed in Novartis’ (NVS, NR) Lucentis and Regeneron’s (REGN, OP) Eylea, which we think would limit its success to be a real player in the space.
Investors seem to be sitting this one out for now. Allergan $AGN shares are slightly in the red this morning, dipping 0.33%, or $0.5, pre-market.
The duo has previously touted Phase III data suggesting abicipar is non-inferior to Lucentis on both tested schedules, though the incidence of intraocular inflammation remained a sore point given that less than 1% of the patients on the rival drug experienced it.
Where Allergan is hoping to stand out is the dosing regimen, a fixed 12-week regimen that could “greatly reduce the treatment burden” according to Cleveland Clinic Cole Eye Institute’s Peter Kaiser. That’s thanks to Molecular Partners’ DARPin technology, which it says has higher stability and potency than monoclonal antibodies.
A BLA is still slated for the next two months, Allergan and Molecular Partners say, as previously reported.

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