It always looked as if it might be a bit of a stretch and Wednesday an FDA advisory committee almost certainly snapped any hopes that NicOx (OTCPK:NICXF) would garner FDA approval for its osteoarthritis drug naproxcinod by the expected PDUFA deadline of July 24.
While the company is still pointing to the fact that the FDA does not have to follow the recommendations of its advisory committees, and certainly recent decisions such as the rejection of InterMune’s (NASDAQ:ITMN) pirfenidone have demonstrated that it can overturn opinions, the pretty clear vote of 16-1 against approval which triggered a 45% plunge in the shares Thursday to €2.90 indicates that few others think a thumbs up is likely.
Instead of the positive recommendation that NicOx had been hoping for with naproxcinod, a version of pain killer naproxen with a nitric oxide donating molecule, the panel instead suggested new outcome studies, which are almost certain to delay approval for years to come (Event - NicOx could be facing painful adcom, May 11, 2010).
What the panel did agree was that naproxcinod is better than placebo, small comfort for the group which was trying to prove that the drug is comparable to naproxen, which the panel could not agree on. The rationale behind naproxcinod has been built around the fact that the drug was supposed to address the worrying cardiovascular (CV) and gastro intestinal (GI) safety concerns of naproxen and without these claims it is just another version of a now generic pain killer.
The panel pointed to the fact that the drug had failed to meet the primary endpoints in two out of three blood pressure studies and more concerning, questioned whether the incidence of stroke, heart attack or death would be better indicators of clinical outcome than blood pressure.
The GI safety data was also deemed to be taken from samples too small, with the trials themselves seen as too short and not including enough high risk patients. As such with large questions over the efficacy and safety of the product it would be a huge volte face for the FDA to approve the drug, despite the lack of treatments that avoid the common problems with NSAIDS.
What this negative opinion from the FDA does is leave the question what does NicOx do next? At a bare minimum the panel’s recommendations leave NicOx looking at very long and extensive trials to prove not only the efficacy of naproxcinod to naproxen, but also its claims of superior safety.
The final detail of any trials that NicOx will have to undertake if it fails to get approval will not be known until it has its discussions with the FDA in the event of a complete response letter. But if the 26,000 patient Ontarget trial conducted by Boehringer Ingelheim to prove the reduction in cardiovascular risk attributed to Micardis are used as an indicator, NicOx could be looking at the prospect of a four or five year trial involving tens of thousands of patients.
This does not look like an achievable task for the French pharma company, despite its outstanding record in raising cash, which currently stands at $269m. While investors were willing to stump up €100m ($125.7m) in a series of fundraisings last year, albeit at a huge discount, these were all undertaken on the promise that the company would get approval and a US partner would follow, triggering a huge uplift in the share price.
Given the outcome of Wednesday’s advisory committee, which has sent the shares down to seven year lows, the chances of NicOx turning again to the markets to fund trials looks slim. The group also has already spent quite considerable sums on R&D, almost $280m in the five years ending in 2009, with little to show for it.
As such, with few hopes of success in the US, attention could be turned to naproxcinod’s fate in Europe where the drug is expected to hear whether it has been granted approval by July 20. But given the outcome of the advisory committee it would be a brave person putting the odds of success above 50/50 here.
However, one of the obvious winners in the midst of NicOx’s misery could be Pozen (NASDAQ:POZN) and AstraZeneca’s (NYSE:AZN) Vimovo, which earlier this month got approval for its combination of naproxen and a proton pump inhibitor ('Safer' NSAID meets FDA muster but awaits European and commercial judgement, May 4, 2010). Shares in Pozen were 9% higher in early trading Thursday at $9.11.