ARESEARCH TRIANGLE PARK — Can you imagine the heartburn that must have been raging out of control among Pozen executives over the l-l-l-o-o-n-g Memorial Day weekend?

On Friday, Pozen management took a huge blow to the midsection when the “non-approvable” letter for its proposed migraine headache drug MT100 arrived from the FDA. The heartburn triggered by the news had to be absorbed silently until Tuesday morning when the news about the rejection was issued in a press release before the markets opened.

The heartburn had to worsen as executives conducted a conference call, expressing “shock” at the FDA decision, and then watching Pozen stock get pummeled for the second time since October when the FDA delivered another knockout blow to a Pozen product.

By day’s end, Pozen (Nasdaq: POZN) stock had dropped a whopping 37 percent, or $3.69, to close at $6.23.

It seems like only yesterday that GlaxoSmithKline and Pozen announced a major deal on migraines that already has put $15 million in the bank for the much-smaller Chapel-Hill based firm.

The stock was trading at over $17 earlier this year, recovering from a drop in October when the FDA dissed MT 300.

“Given the number of patients exposed to MT100 for at least one year in your database, the absence of any detected cases is consistent with a true rate of TD [tardive dyskinesia ] of about 1%, an unacceptably high risk in the absence of any demonstrated advantage of the product,” the FDA wrote in its non-approvable letter for MT-100, according to a wire service report. TD is a neurological disorder.

The landslide in the stock price led to the dumping of 8.5 million shares — more than 20 times the normal daily volume.

The news also triggered a downgrade of the stock by Wells Fargo to “hold” from “buy.” The company had just launched coverage of Pozen in March.

Headlines, such as The Wall Street Journal’s “Pozen’s Credibility Is Hit By Latest FDA Rejection” and SmartMoney’s “Migraine Attack” won’t help.

But Adam Feuerstein, writing for TheStreet.com, saw this train wreck coming. He wrote a story on April 12 warning that test data from Pozen’s two trials for MT-100 triggered “red flags.” He wrote that “Pozen shareholders might be headed for another splitting headache.” Feuerstein pointed out that the FDA required two clinical trials for combo drugs, such as MT-100, which combines an anti-nausea drug and anti-inflammatory drug, must demonstrate statistically superiority to the drugs administered individually and placebo.

One of the two tests didn’t meet that standard, although Pozen insisted that the drug should have been approved and that it will meet with the FDA about the matter.

“We are shocked this latitude appears not to have been given,” said Pozen CEO John Plachetka in the conference call, referring to the test data and what he thought was an understanding with the FDA about meeting so-called study endpoints, “but until we have the discussion with the FDA, there could be another issue we’re not aware of.”

Pozen also has another migraine drug in the pipeline, but after going 0-for-2, what’s next?