Welcome to your weekly digest of approaching regulatory and clinical readouts. While Regeneron concentrates on the fallout from the patent lawsuit over Praluent, its cholesterol treatment, it is looking to expand the franchise for Eylea. Phase II results of its combo REGN910-3 in diabetic macular oedema are expected shortly. Last year a different Eylea combo failed, and its patent expiry is looming.
And data from the remaining phase III trials of Lundbeck’s idalopirdine in Alzheimer’s disease are expected in the first quarter; the first trial failed, and there is little hope for the two ongoing studies as Alzheimer’s continues to elude drug developers.
REGN910-3 is a co-formulation of nesvacumab, which targets angiopoietin-2, and Eylea. The diabetic macular oedema trial, called Ruby, has completed its 304 patient recruitment, testing two doses of REGN910-3 versus Eylea.
The primary outcome is change from baseline in best corrected visual acuity (BCVA) at 12 weeks, and data could come in February. Secondary endpoints include this measure at 36 weeks.
The second trial, Onyx, is still recruiting, with an aim of signing up 360 patients with wet age-related macular degeneration. This trial has the same primary measure as Ruby.
In October a co-formulation of Eylea and the anti-PDGF MAb rinucumab, called REGN2176-3, failed in phase II. Patients given just Eylea had a greater improvement in BCVA at 12 weeks, and there were more adverse events in the combo arm (Regeneron failure is one in the eye for Ophthotech, October 3, 2016).
With global patents set to expire between 2020 and 2026 Regeneron and its partner Bayer are trying to get a headstart on Eylea competitors. Roche’s anti-VEGF/Ang2 bispecific antibody RG7716 is in a phase II trial called Avenue in wet age-related macular degeneration, results of which could come before the end of the year.
Meanwhile, data from the remaining two trials of Lundbeck and Otsuka’s idalopirdine are expected in the first quarter. The Starbeam study is testing idalopirdine in 858 patients with mild to moderate Alzheimer’s disease, looking at 10mg or 30mg doses on top of 10mg of Aricept.
Starbright, meanwhile, has recruited 734 patients and evaluates 30mg or 60mg doses in combination with an unnamed acetylcholinesterase inhibitor – the same drug class as Aricept. Both trials have placebo and Aricept arms for comparison.
Last September the 932-patient Starshine trial failed to show a benefit for idalopirdine on its primary endpoint, the ADAS-cog score at either a 30mg or 60mg dose. The project was added on top of 10mg of Aricept and pitted against Aricept plus placebo; it also failed to show an improvement on secondary endpoints (Spotlight on Axovant after Lundbeck’s Alzheimer’s failure, September 23, 2016).
The lack of efficacy could have been a result of the relatively low dose, necessary because the 90mg used in phase II was linked with liver toxicity. Lundbeck shares fell 15% on the Starshine failure while its partner Otsuka declined 3%.
Many analysts have wrote off idalopirdine after its first failure. Axovant, whose intepirdine has a similar mechanism to idalopirdine, also suffered, with its shares falling nearly 13% on the Lundbeck news; phase III data for Axovant could come before the end of the year. Notably Pfizer’s similar asset PF-05212377 was discontinued a couple of years ago owing to lack of efficacy.