In a bid to resurrect investors'--and perhaps potential European partners'--interest in its beleaguered COPD drug aclidinium (branded as Eklira), Almirall announced this week that it plans to file in Europe early in 2010, almost two years earlier than expected after disappointing Phase III data last year forced a re-think.
When Spain's largest pharmaceutical firm listed 30% of its share capital back in 2007, mouths were watering at the growth story it represented: here was a mid-sized group (2008 sales: €900 million) with a potential €2 billion drug in its pipeline that could double or treble the company's size overnight.
The drug was aclidinium, a long-acting muscarinic agonist in the same class as Pfizer/Boehringer Ingelheim's Spiriva. And it had a super-duper, easy-to-use device to go with it--better than Spiriva's. Unfortunately, Phase III results showed far lower efficacy than expected and fell short on two critical secondary end-points (quality of life, time to exacerbation).
The stock fell 40%, and continued downwards to a low of about €5 in October that year. Having ridden the 'exciting newcomer' wave in the public markets for a while, Almirall came splashing down. Phase III would have to be re-done, the company said, setting aclidinium back two years in a competitive, Big Pharma-dominated marketplace.
So why the change of heart, in Europe, anyway? Apparently because of two small but significant trials, one looking at onset-of-action (vs Spiriva), and the other at exercise endurance (vs placebo). The studies involved only 115 and 181 patients respectively--small fry compared to the 1600 or more patients treated in the Phase III studies.
But Almirall reckons these trials might just be enough to build a satisfactory submission to the authorities for once-daily use. "The exercise limitation study is a big deal," asserted Prof. Paul Jones from London's St. George's Hospital in the UK on a conference call to discuss the new plans, "because tiotropium [Spiriva] didn't show a clinically worthwhile response from day one, but only a slow improvement over the six-weeks of its study," he said. (Almirall's exercise study didn't compare aclidinium and Spiriva head-to-head.)
Now granted, secondary end-points such as these are important in Europe, perhaps more so than in the US. But an approval--certainly in one cycle--is still probably a long-shot. Sure, Almirall's original Phase III trials met their primary end-points (improvement in lung function vs placebo), but they met them with far-from-flying colors. For FDA, this was a non-approvable package, full stop (and Almirall and US partner Forest Labs haven't altered their expected US filing date of late 2011/early 2012).
Safety and tolerability might have been great, but efficacy was missing, at least with a once-daily dose--which is why the partners are now running a study using twice-daily dosing vs placebo in the US. What's more, European regulators like head-to-head studies, which Almirall doesn't have (apart from the small secondary ones).
Still, "they've got nothing to lose," comments one analyst. "I suspect they may have to top-up the submission with additional data," the analyst continues--probably from the US study--"but this way at least they get the process going." Not a bad idea, given that Novartis' once-daily LABA indacaterol has shown promising Phase III data this year.
And perhaps Almirall's bullish news will trigger some interest among potential European partners for the drug, for which the hunt's still on. (With a smaller drug, Almirall might be stepping up its own commercial participation, however; even before the disappointing Phase III data, the company told IN VIVO it would like to at least participate in the key five markets.)
Indeed, this surprise move hasn't changed analysts' sales forecasts for the drug--most still sit at about $200 million in Europe, a fraction of the multi-billion dollar figures of yesteryear. Nor will it alter the fact that aclidinium isn't going to push Spiriva off its post. Far from it; with lesser efficacy "it will be the second choice to Spiriva, there's no way round that," says the analyst.
But Almirall's not Pfizer, so a $200 million 'niche' drug would still be very useful--if far from transforming.
--Melanie Senior (m.senior@elsevier.com)
This article first appeared in The IN VIVO Blog, which you can access here—or sign up for the IN VIVO Blog RSS feed here.
