Washington Editor

Jazz Pharmaceuticals Inc.'s failure Friday to convince an FDA panel that the company could safely market its sodium oxybate drug JZP-6 as a treatment for fibromyalgia had investors singing the blues Monday.

Shares of the Palo Alto, Calif.-based specialty pharma (NASDAQ:JAZZ) plummeted 22.2 percent, or $2.27, to close at $7.96.

Citing mostly fears about the potential for abuse of sodium oxybate – whose active ingredient, gamma-hydroxybutyrate, or GHB, is known as the notorious "date rape" drug – panelists at a joint meeting of the FDA's Arthritis and Drug Safety and Risk Management Advisory Committees Friday voted 20 to 2 that JZP-6's risk-benefit balance did not favor its approval as a treatment for fibromyalgia. (See BioWorld Today, Aug. 23, 2010.)

Jazz markets sodium oxybate 500-mg/mL under the brand name Xyrem as a treatment to reduce daytime sleepiness and cataplexy in patients with narcolepsy. But the company wants to sell it at a lower dose under the name Rekinla for fibromyalgia. The FDA, however, has yet to sign off on that trade name.

Even before last week's panel meeting, regulators had expressed concerns about having two separate brand names to market essentially the same drug. The agency also was worried about having two risk evaluation and mitigation strategy (REMS) plans for Xyrem and Rekinla. (See BioWorld Today, Aug. 19, 2010.)

Given those concerns, a "no" vote "wasn't shocking," said Jefferies & Co. analyst Corey Davis.

But he blamed the "landslide result" of the vote on "other misguided fears and unrealistic expectations.

Nonetheless, Davis said he expected the FDA to see past the panel's apprehensions.

Davis accused one panelist's views, those of Thomas Kosten, a professor of psychiatry and addiction at Baylor College of Medicine in Houston, of muddling the committee.

Kosten had insisted throughout Friday afternoon's debate that an approval of sodium oxybate in fibromyalgia would lead to GHB flooding the streets, resulting in rampant abuse, similar to the ongoing problem with Purdue Pharma LP's extended-release oxycodone drug, OxyContin.

"This sentiment led many panelists to hold Xyrem to an unrealistically high REMS hurdle," Davis said. "We find this absurd." He noted that the FDA's proposed classwide REMS for opioids is not as strict in many ways as the current REMS for Jazz's Xyrem and the one the company has proposed for JZP-6. (See BioWorld Today, Feb. 17, 2009, June 1, 2009, Dec. 7, 2009, and July 26, 2010.)

For one thing, the classwide opioid REMS does not call for a restricted distribution program, nor does it include patient and prescriber registries, Davis noted. "No REMS is perfect, but we believe with a few tweaks, the FDA should be more than satisfied with Jazz's efforts," Davis argued.

While he said it was "tough to bet against" the panel's 20-to-2 vote, "we believe the majority of concerns are not shared by FDA, and 2011 approval is still realistic."

After all, he noted that Bob Rappaport, director of the FDA's Division of Anesthesia and Analgesia Products, counseled Friday's committee before its vote that "voting no to approve at this time doesn't mean that you are voting that it should never be approved."

Panelists could vote no and then "tell us afterward what the company needs to do to get this into shape to be approved," Rappaport said Friday.

"You could think that this is a really important addition to the armamentarium for the fibromyalgia community and if that is what you think, that is fine, but that shouldn't necessarily mean your vote has to be yes at this time," he added. Rappaport emphasized, however, that he was not trying to tell the committee which way to vote.

Davis said that Rappaport's words "clearly signal" the FDA likelihood of approving sodium oxybate for fibromyalgia, despite the negative vote.

He also noted that Rappaport "more purposely than usual" highlighted how "helpful" the public speakers were at Friday's meeting, with 14 of those 16 speakers backing approval of sodium oxybate for fibromyalgia.

Some of those speakers, however, had their transportation to the meeting paid for by Jazz.

If the FDA issues a complete response letter by the Oct. 11 Prescription Drug User Fee Act action date, but does not request additional studies, "that should validate our conclusion," Davis said.

CEO Bruce Cozadd told BioWorld Today Monday that the firm is seeking a meeting with the FDA before Oct. 11, and would "move quickly" to address the concerns raised by the agency's panel. "We do believe that it is possible with an effective REMS program to protect the safety of patients and the public and yet make this drug available to the fibromyalgia patients who clearly are in need of additional treatment options," Cozadd said.

He said it was "difficult" now to predict "exactly when things will happen or exactly what will happen."

Cozadd noted that while Xyrem's approval in narcolepsy did not come easy, it now "has proven to be a very important treatment option for narcolepsy patients and designated as a standard by the American Academy of Sleep Medicine."

The risk program for Xyrem, which has been in place for eight years, "has in fact proven successful in allaying the concerns that might have been raised at the time of its approval," he contended.

Cozadd said his firm is concentrated on "being safe and responsible" in how it brings JZP-6 to market "so that we do get that benefit without the risks that were certainly the focus of the conversation Friday."

"It's all about the balance between that benefit and risk, and we want to make sure that we and FDA both get comfortable with, whichever way we go, that the benefits do outweigh the risks," he said.