Lagging behind three big rivals, Alder’s migraine project eptinezumab needed a knock-out result in the pivotal Promise 1 trial to compete. But the benefit, although statistically significant, was far from impressive, sending Alder’s stock down 28% yesterday.
While the usual caveats about across-trial comparisons apply, eptinezumab’s efficacy seems slightly inferior to that of the other CGRP inhibitors (see table below). Although approval appears likely, Alder needs more cash to support the project’s launch, and it is hard to see where the money will come from, with eptinezumab looking more like an also-ran.
Some sellside analysts tried to talk up eptinezumab’s advantages, including a fast speed of onset and less-frequent dosing: every three months versus monthly with the rival anti-CGRPs. However, the trade-off is that Alder’s project is given intravenously, while the others are subcutaneous, which could cancel out any convenience benefit.
Alder has been working on a subcutaneous version of eptinezumab, but company executives were reluctant to talk about this during yesterday’s conference call, fuelling doubts about its future. If this project has been shelved, as some fear, it would be another nail in the coffin for Alder after the underwhelming Promise 1 data.
|How the anti-CGRPs stack up|
|Project||Company||Migraine type||Efficacy vs placebo||Study||Next steps|
|Erenumab||Amgen/Novartis||Episodic||1.1 days||Arise (phase III), NCT02483585||Filed in both chronic and episodic May 2017|
|Episodic||1.4-1.9 days||Strive (phase III), NCT02456740|
|Chronic||2.4 days||Phase II study, NCT02066415|
|Galcanezumab||Lilly||Episodic||1.8-1.9 days||Evolve-1 (phase III), NCT02614183||Filing H2 2017|
|Episodic||1.9-2 days||Evolve-2 (phase III), NCT02614196|
|Chronic||2 days||Regain (phase III), NCT02614261|
|TEV-48125||Teva||Episodic||1.5 days||Halo EM (phase III), NCT02629861||Filing later in 2017|
|Chronic||2.5 days||Halo CM (phase III), NCT02621931|
|Eptinezumab||Alder||Episodic||0.7-1.1 days||Promise (phase III), NCT02559895|
|Chronic||~2-2.8 days*||Phase II study, NCT02275117||Phase III Promise 2 data due H1 2018|
|*Estimates from data presentation.|
While the trial, in episodic migraine, was technically a success, it provides further evidence of the marginal benefit that the anti-CGRPs offer. This seems even slimmer with eptinezumab: the placebo-adjusted reduction in monthly migraine days with a 100mg dose was just 0.7 days, which rose to 1.1 days with 300mg.
Leerink analysts put some of the blame on a larger placebo effect in Promise 1. Alder also suggested that, in general, the placebo response is higher with intravenous versus subcutaneous therapy.
However, this all sounds like clutching at straws, particularly when considering the poor performance of the 100mg dose and the implications for the subcutaneous project. Here, moving forward with the lower dose would have been preferable as larger volumes are more difficult to administer via this route.
Indeed, Alder suggested that if the 300mg dose was clearly better it might instead choose to develop an intramuscular formulation for self-administration, Leerink analysts noted, which could struggle to compete against its subcutaneous rivals.
Alder is expecting data from the Promise 2 trial in chronic migraine next year, and it will need this to file for approval of eptinezumab, planned for the second half of 2018. By this time, all three of its rivals will be under FDA review, and the first might even be approved.
Alder already had a lot to contend with, trailing projects from Lilly, Teva, Amgen and Novartis. Rather than confirming eptinezumab’s promise, the latest data have made its task look even harder.