Welcome to your weekly digest of approaching regulatory and clinical readouts. Allergan’s oral CGRP antagonist atogepant is due to yield phase IIb data in the second quarter in migraine prophylaxis, a crowded market that could see MAbs launched by the end of the year. Allergan will have to play on its oral advantages.
And, as Eylea sales look set to flatten, Regeneron’s franchise extension efforts now hinge on data from the phase III Panorama trial, expected by mid-year. This study tests Eylea as a monotherapy in diabetic retinopathy without diabetic macular oedema (DMO).
Allergan already has positive data on one oral anti-CGRP: ubrogepant in acute migraine. Now it is the turn of atogepant, in episodic migraine prophylaxis.
The latter’s phase IIb trial in 1,200 subjects should generate top-line data by the second quarter. Five different doses are being tested, with either once or twice-daily administration versus placebo. The primary endpoint is change from baseline in mean number of migraine days.
The prophylactic migraine market could see the US entry of the first injectable MAbs targeting CGRP by the end of the year. Amgen and Novartis’s Aimovig has a PDUFA date in May, while Lilly’s galcanezumab will come before regulators in the second half of the year. Teva’s fremanezumab had a mid-year PDUFA date, but a recent FDA warning letter at its manufacturing plant could cause a delay.
Phase III results have been similar between the different MAbs, with the usual caveats about across-trial comparisons. Lilly’s galcanezumab looks to be the best in episodic migraine, reducing the number of monthly migraine days by 1.9 to 2 days versus placebo (Alder on a Promise, but it could be too late, January 8, 2018).
The main investor concern for oral CGRPs is liver toxicity, with Merck’s telcagepant shelved in 2011 owing to elevations in alanine aminotransferases (ALT). Some reassurance came on Allergan’s recent quarterly earnings call when the group said there was only a 1% incidence of ALT elevations three times the upper limit of normal in its blinded phase IIb study of atogepant.
However, Allergan has some catching up to do as it will likely be fifth to market, also behind Alder’s eptinezumab, which is expected to be filed by the end of the year. With a pill Allergan is in a unique position, and it needs to make the most of its this if it is to make up ground.
|Late-stage prophylactic migraine projects targeting CGRP|
|Global sales ($m)|
|Filed||Aimovig (erenumab)||Amgen/Novartis||109||1,223||PDUFA 17 May|
|Phase III||Eptinezumab||Alder Biopharmaceuticals||-||395||Expected to be filed by YE|
|Atogepant||Allergan/Merck & Co||-||55||NCT02848326|
Broadening its label
Regeneron has tried and failed to extend its Eylea franchise through combinations, and competitors are hot on its heels. With Eylea’s patent due to expire in 2023 it looks like future growth hinges on its result in diabetic retinopathy.
The phase III Panorama study is due to read out by mid-year. In this, some 400 patients with moderately severe to severe non-proliferative diabetic retinopathy without DMO were randomised to receive one of two intravitreal Eylea doses or sham treatment.
The co-primary endpoints are the proportion of patients improving by at least two levels from baseline on the diabetic retinopathy severity scale at weeks 24 and 52.
Key secondary measures include the proportion of patients who develop DMO, and time to development of a vision-threatening complication through the first two years, which will likely be presented in 2019 rather than this year.
While Eylea is approved in the US for diabetic retinopathy and DMO, Panorama is notable in testing non-proliferative diabetic retinopathy and excluding DMO. Although DMO, the most common cause of vision loss in diabetic retinopathy, is more likely to occur as diabetic retinopathy worsens, it can happen at any stage of the disease.
Leerink analysts note that the biggest hurdle will be convincing individuals that they should receive an injection to prevent progression of disease that may be years away; symptoms typically do not become apparent until non-proliferative diabetic retinopathy progresses to the proliferative type and major bleeding in the retina occurs.
The data will need to show that treatment is best started earlier, when there is more vision to be saved and a higher chance of avoiding serious complications like retinal haemorrhages or tears.
|Global sales ($m)|
|Regeneron||3,902||4,116||4,173||USA; Japan (33.5-40% royalties); WW ex USA & Japan (50:50 profit-share with Bayer for eye diseases)|
|Bayer||2,387||2,706||2,472||WW ex USA & Japan (50:50 profit-share with Regeneron); Japan (co-promotion with Santen)|
|Santen||467||451||340||Japan (co-promotion with Bayer)|