(Adds Pozen comments, NEW YORK dateline)
By Ben Hirschler and Bill Berkrot
LONDON/NEW YORK, Aug 2 (Reuters) - U.S. regulators have delayed approval of an experimental two-in-one migraine drug from GlaxoSmithKline Plc (GSK.L) and Pozen Inc. POZN.O yet again, sending Pozen shares down 45 percent on Thursday.
Glaxo said the U.S. Food and Drug Administration had asked Pozen to address the potential implications of a preclinical study into chromosomal risks, in which genotoxicity was seen the combination drug called Trexima, but not with either of the components on their own.
Analysts said the problem could delay the drug’s launch until mid-2008 and reduce significantly its sales potential.
Trexima combines Glaxo’s Imitrex -- the most widely used of the multibillion-dollar class of migraine drugs known as triptans -- with the common, older painkiller naproxen. The combination attacks different pathways in the brain and is designed to act faster and last longer.
The product has faced previous delays in getting to market and many investors had been counting on the FDA to give it a green light this time. Instead, the agency issued a second “approvable letter” -- an official notification containing conditions that must be satisfied prior to obtaining final U.S. marketing approval.
Glaxo and Pozen intend to request a meeting with the FDA as quickly as possible to discuss the necessary steps to address its concerns.
“Anything is possible at this point except getting approval this week,” Pozen Chief Executive John Plachetka told analysts on a conference call.
He said the best case is a delay of “no less than two or three months, and it could take longer than that.”
“The likely scenario is that we’ll need to submit some new information to help (the FDA) over their discomfort on this finding. Whether it’s expert testimony or new data is not known at this time,” Plachetka said.
The cause for concern came from a test that involved doses of 100 times the normal human therapeutic dose, Pozen said, adding that three similar tests did not find genotoxicity.
Company scientists suspect that the genotoxic finding was an anomaly having to do with the way the compound reacts in that particular test, the CEO said.
He said it was likely the FDA would ask for a small, single dose test in humans that would produce data that could be interpreted very quickly.
“We will lobby very strongly for them taking this under a two-month review,” Plachetka said. “It depends on the agency’s work load, but if you handed this study to a scientist, you could have your answer in less than an hour.”
The problem of a delay is that it reduces the time Glaxo and Pozen have to switch patients to the new drug before cheap generic copies of Imitrex hit the U.S. market in late 2008.
“At this stage it is impossible to say how long the delay will be. However, assuming that launch does not take place until May/June 2008, that reduces the window to switch patients from Imitrex to Trexima ... to just six to seven months,” Marck Purcell of Deutsche Bank said.
Purcell said he was cutting his 2012 Trexima sales forecast to 352 million pounds ($715 million) from 556 million.
Cowen & Co analyst Ian Sanderson cautioned, “if this lingers for an extended time, there is a chance Glaxo could scrap the program.”
Earlier FDA concerns had centered on the heart safety of Trexima. No additional information was requested on this aspect of the product, but both companies agreed to conduct a study on its effects on blood pressure after approval.
“We all know it’s a difficult regulatory environment. We have examples every day,” Plachetka said.
“I find it difficult to believe that this is really a true risk,” he added. “The agency just wants more confirmation so they can say we ran it down.”
Pozen shares were down $7.85 to $9.60 in midday trade on Nasdaq. Glaxo shares closed up nearly 2 percent at 12.79 pounds in London.
Shares of Europe’s biggest drugmaker have rallied this week on relief that its diabetes pill Avandia is set to remain on the U.S. market, despite a report in May linking it to heart-attack risk. (Additional reporting by Ransdell Pierson in New York)