March 29, 2012: Forest has announced that the PDUFA date for aclidinium bromide will now take place in July due to a three-month extension from the FDA to review the NDA data.
Forest Labs will take comfort from a surprisingly benign review of its COPD therapy aclidinium bromide by an FDA advisory panel yesterday. Up for a final US decision by the end of April, concerns about heart safety could still stymie approval but the almost unanimous backing by the panel raise the chance of a green light straight off.
A long-acting inhaled anti-muscarinic agent (LAMA) that will compete with blockbuster incumbent Spiriva, analysts are not expecting great things from aclidinium initially. Viewed as less effective than Spiriva, greater potential is seen in a product that combines aclidinium with a bronchodilator – results should emerge from phase III trials early next year. But this approval would be a welcome first step and the drug will be the first direct competitor to a product that sold $2bn in the US last year - an opportunity that Forest will be going all guns to capitalise on.
The FDA panel gathered to review aclidinium voted 12 to 2 in favour of approving the drug. Separately, the advisors voted unanimously that the drug is effective and 10 to 3 with one abstention that it is safe.
Briefing documents released earlier in the week raised FDA fears about heart problems, particularly in the light of concerns over other drugs in the class. Spiriva was linked to stroke but an FDA review in 2010 found no evidence of cardiovascular risk associated with the drug, sold by Boehringer Ingelheim and Pfizer.
An apparent imbalance in cardiovascular deaths in trials with aclinidium was apparent, although could not be proved a true safety signal, the agency pointed out. Panel members were also mindful of this signal, and post marketing research was recommended, to rule out any risk.
The FDA’s verdict is now awaited and critical will be whether the agency wants further evidence of the drug’s heart safety, before it allows aclinidium on the market. Panel members also expressed interest in seeing a head-to-head study versus Spiriva, possibly incorporating an active comparator arm into a post marketing safety study. Given that many analysts view the drug’s efficacy to be inferior to Spiriva, is seems unlikely Forest would be keen to pit the drug directly against the market leader.
Consensus forecasts for the drug currently stand at sales of $217m in 2016, with analysts pencilling in a launch this year (Event - Forest counting on Eklira to kick start new sales growth, February 16, 2012). The numbers will largely reflect sales of the drug as a monotherapy.
Considered equal at best to Spiriva in terms of efficacy, the product could struggle to make significant headway and it will be interesting to see how competitively Forest prices the product. Forest and European partner Almirall, which sold US rights back in 2006, started a 3,500 patient phase III programme of aclidinium plus the long acting beta 2 adrenoreceptor agonist (LABA) formoterol last November. Two 24 week phase III trials will be run in Europe and the US plus a 52 week long term safety study.
Of course these partners are not alone in seeking to improve the treatment of COPD with a LAMA-LABA combination. Novartis and GlaxoSmithKline both have similar products in development. The Swiss pharma giant is slightly ahead with QVA149 although doubts remain whether this will be a once-a-day product while Glaxo’s GSK573719/vilanterol could start to yield phase III results later this year.
Boehringer is also working on a LAMA/LABA combination, adding a novel bronchodilator olodaterol to Spiriva; a phase III programme started last September.
But should aclidinium receive approval in the US, it will be only the second LAMA on the market for COPD. The closest competitor is probably Novartis’ NVA237, but delays mean that is unlikely to be filed until 2013.
So aclidinium might not be the most potent LAMA, but it could well be the only competitor snapping at Spiriva’s heels. Selling $4.38bn last year, half of which is thought to have come from the US, that is not a small market to be entering.