Poor Phase III data nearly halved DOV Pharmaceutical Inc.'s stock value Tuesday after the findings were unveiled late Monday.
Top-line results showed that the Hackensack, N.J.-based company's analgesic bicifadine failed to relieve patients' chronic low back pain, at least to a statistically significant degree compared to placebo, at any of the three doses tested. In a conference call, DOV President and CEO Leslie Hudson blamed the "unexpected outcome" on an "unusually high" placebo response rate as one possible reason for the outcome, as well as the extent of patients' reliability in taking their medication. "Both of these are potential factors," he said.
On Tuesday, DOV's stock (NASDAQ:DOVP) fell $6.19 to close at $8.50, a 42 percent plunge. An analyst who follows the company said the study's outcome was unexpected.
"It was a surprise," said Juan Sanchez of Punk, Ziegel & Co. in New York. Noting that the mechanism of action of the non-opioid drug's class is understood "very, very well," he pointed to the subjective nature of pain studies as a common hurdle faced by all prospective therapies being developed. "This doesn't mean that the drug is bad," Sanchez added.
Labeled study 020, the trial evaluated twice-daily doses of bicifadine at 200 mg, 300 mg or 400 mg. Its primary endpoint measured patients' improvement in Visual Analogue Scale (VAS) pain scores between baseline and the end of the treatment period, which lasted up to 12 weeks. Specific data were not disclosed, but Hudson said DOV is conducting a more detailed assessment of the data in order to better understand the factors that are responsible. Beyond that, he and other company officials were tight-lipped.
"What we want to see are the data," Sanchez told BioWorld Today, "to determine whether its analgesic effect is good enough for a chronic pain setting."
The double-blind study treated about 600 patients at multiple sites throughout the U.S. It is the first Phase III trial of bicifadine in chronic low back pain, and two additional Phase III trials in the same indication, studies 021 and 022, will continue to test the compound as planned. Study 021 has a similar design to 020, with data likely to come by the end of this year, while study 022 is an open-label safety trial.
The same goes for Phase II studies of bicifadine in osteoarthritis and neuropathic pain. Should chronic low back pain not prove to be a viable indication, Warren Stern, the company's senior vice president of drug development, said during conference call that "it's highly likely" that the compound would work well in one of the other indications.
Sanchez, who said that the initial findings shouldn't lead the company to fully abandon the program, nonetheless encouraged a cautious outlook, advising a "wait-and-see approach." At the very least, the negative data point to a delay of probably at least a year before DOV can file for bicifadine's approval, given that the company will need at least two positive Phase III studies for registration.
The osteoarthritis study, which is designed to evaluate bicifadine alone and in combination with ibuprofen, is expected to complete dosing next quarter. That's the same time frame for the study in patients with painful diabetic peripheral neuropathy, a trial designed to assess bicifadine's efficacy and safety and potential interactions when used concurrently with oxycodone.
The biopharmaceutical company will provide more detailed guidance regarding the total program "when we're able to do so," Hudson said.
DOV has rights to bicifadine by way of a licensing arrangement with Wyeth, of Madison, N.J. Another DOV compound in-licensed from Wyeth, indiplon, is under FDA review for insomnia. A decision is expected next month. Its new drug application was filed by DOV's partner, Neurocrine Biosciences Inc. in San Diego.
Sanchez said DOV's deflated share price reflects the value of indiplon, plus the company's existing cash reserves, which stood at $97.6 million on Dec. 31.