Staff Writer

After a failed first attempt, Chelsea Therapeutics International Ltd. reported that Northera (droxidopa) hit the mark in a study of patients with neurogenic orthostatic hypotension (NOH), a drop in blood pressure when taking a standing position.

On the second try, the study met its main goal of improving the composite score of several symptoms, including dizziness, and increasing daily function.

Shares in the Charlotte, N.C.-based company popped 13.2 percent on news of the positive study results.

It was a welcome turnaround from a year ago when the droxidopa's Phase II miss caused the company's shares to drop 61 percent.

The difference between the studies is that the first used just one symptom, dizziness, as the primary endpoint, while the amended study scored multiple symptoms. "Eight out of 10 reached statistical significance," Simon Pedder, president and CEO of Chelsea Therapeutics, told BioWorld Today.

Given its more than 15-year marketing history in Japan, droxidopa actually was expected to do well the first time it was tested in a Phase III trial (Study 302) in patients with NOH. So it caught investors – and Chelsea – by surprise when that first study failed to show statistically significant results.

After conducting a retrospective analysis, Chelsea believed it would have a better shot at proving the drug's efficacy if it had used a different trial design. And in a rare turn of events, the FDA agreed to let the company amend the study endpoints (See BioWorld Today, Sept. 25, 2009, and March 9, 2010.)

But it is unclear whether the FDA would require two positive studies in support of a regulatory filing for droxidopa in NOH.

Juan Sanchez, an analyst with Ladenburg Thalmann, told BioWorld Today, "It's not my working assumption. . . . It's a possibility, but you shouldn't count on it."

As it stands now, Sanchez said, Chelsea appears to be "in a good position" as one of the few companies with a late-stage asset aimed at the central nervous system that has a novel mechanism of action.

Droxidopa essentially works by replenishing depleted norepinephrine, the neurotransmitter used by autonomic nerves to send signals to the blood vessels and the heart.

If approved, droxidopa also is unlikely to face competition, given the troubles of the currently marketed NOH treatment.

The only FDA-approved drug treatment for NOH is generic midodrine, but it carries a black-box warning for supine hypertension (increased blood pressure when sitting or lying down) that has limited its use. It could soon fade from the market now that the FDA has started proceedings that could end in the drug's withdrawal or restricted access.

"We see midodrine may well be coming off the market," Keith Schmidt, Chelsea's vice president of marketing and sales, told BioWorld Today.

By the FDA's estimates, there are about 100,000 patient currently taking midodrine.

Chelsea puts the estimate closer to 65,000, but midodrine isn't used by the entire NOH population due to its side effects.

An additional 30,000 to 60,000 NOH patients not currently using midodrine potentially could use droxidopa, which was shown to be safe and well tolerated.

Consistent with the first study, the second one showed that droxidopa improved patients' fall rate over placebo (no falls for the drug-treated group vs. 4.3 percent for the placebo group).

Chelsea also is studying droxidopa in NOH patients with Parkinson's disease, affecting an estimated 140,000 patients in the U.S.

That pivotal trial (Study 306) is expected to report data in the second quarter of next year.

In addition, the company is studying the drug as a possible treatment for attention deficit disorder, with data expected early next year.

Chelsea's other main program is focused on antifolates aimed at diseases like rheumatoid arthritis and psoriasis.

Shares in Chelsea (NASDAQ:CHTP) were up 67 cents, closing at $5.73 Monday.