West Coast Editor
Full results come later, but favorable 30-minute results with BioDelivery Sciences International Inc.'s polymer fentanyl disc in a Phase III study for breakthrough cancer pain sent shares rocketing skyward - and brought BDSI another step closer to taking on Cephalon Inc.'s franchise in the space, where patients are still widely untreated, BDSI said.
Shares of Morrisville, N.C.-based BDSI (NASDAQ:BDSI) gained more than 30 percent Wednesday to close at $6.05, up $1.31, after trading as high as $8.26 on word that the firm's BEMA Fentanyl hit the primary efficacy endpoint of the 80-patient trial, Summary of Pain Intensity Difference (SPID) at 30 minutes, compared to placebo (p=<0.004).
BEMA Fentanyl is a dissolvable disc that adheres to the inner lining of the cheek, where it dissolves in about 30 minutes. Frazer, Pa.-based Cephalon sells Actiq, a fentanyl lozenge on a stick, and Fentora, a next-generation, effervescent fentanyl tablet.
While shopping for a commercialization partner, BDSI plans a meeting with the FDA at the end of June, said Mark Sirgo, president and CEO, after which the company intends to file its new drug application under Section 505(b)(2), with Actiq as the reference drug.
Sirgo said BDSI has "been in discussions with a number of parties for the last several months," and talks likely will pick up speed now.
Andrew Finn, BDSI's vice president of product development, told investors during a conference call that the last subjects in the Phase III study were enrolled just last month, and full results will be offered at a scientific meeting. Among those data are SPID results at 15 minutes; Fentora has been said to provide relief as early as 10, Actiq at 15.
BDSI said fewer than 50,000 of the estimated 500,000 patients with breakthrough cancer pain are getting treatment, though Russell McAllister, analyst with Merriman Curhan Ford in San Francisco, said leader Cephalon has "more or less tapped out the cancer breakthrough pain market, and have shifted the focus into other types." Actiq and Fentora are "used pretty extensively off label," he added.
Other forms of fentanyl also are used, McAllister pointed out. Suppositories work in about 20 minutes, and oral drugs in 25 to 30. "You're paying a lot of money for an extra few minutes," he said. "A lot of times you would just jack up the dose of the chronic opioid [already being given to the patient] and that would take care of a lot of it."
Actiq made up about 34 percent of Cephalon's total sales last year, and in the fall, Barr Laboratories Inc., of Woodcliff Lake, N.J., launched a generic version that will erode Actiq sales this year. Cephalon has a license and supply deal with Barr, and sells its own generic Actiq through Corona, Calif.-based Watson Pharmaceuticals Inc.
Cephalon's total market volume in breakthrough cancer pain, though, has shrunk year after year by an average of 15 percent, according to a report by Megan Murphy, analyst at Lazard Capital Markets in New York. At the end of March, Fentora held a 27 percent volume share, branded Actiq held 22 percent, and generic Actiq held 51 percent (with 29 percent for Barr and the rest for Watson).
"I wouldn't say [Cephalon's breakthrough cancer pain franchise is] fizzling, I'd say it's growing at a much slower rate than the Street would like to have seen," McAllister told BioWorld Today. "It still pretty solid."
Last fall, Cephalon won approval for Fentora, which also is being developed for non-cancer pain. Finn said BDSI would go after non-cancer pain, too, though the firm must do "substantial preclinical work." He said approval in other pain indications such as neuropathic and low back - to be sought by Cephalon with Fentora - would require two studies of carcinogenics, one toxicology study, and a placebo-controlled trial, as well as long-term safety data, following 300 patients for at least six months and 100 for a year.
Meanwhile, the buzz is about cancer pain. The Phase III trial with BDSI's two-layer disc followed the same design as those for Actiq and Fentora, the company said, and BEMA Fentanyl showed better linearity (more drug matched more serum concentration), though the compound has not been compared in a head-to-head trial with either Cephalon drug.
Only five patients, or about 3 percent of those who entered the first, titration part of BDSI's study, were unable to get relief, apparently because of BEMA Fentanyl's ease of application across a wide range of doses, up to 1,200 mcg. None showed irritation or ulceration of the mucosal lining - especially important in a patient group that may be getting radiation or chemotherapy, which already compromises the membranes. Fentora's package insert described 10 percent of tested patients showing mucosal irritation and 3 percent ending up with mouth ulcers.
Praising BDSI's data, McAllister cited another would-be Cephalon competitor in Phase III Rapinyl, a sublingual mucoadhesive fentanyl product. Endo Pharmaceuticals Inc., of Chadds Ford, Pa., entered a deal with the Swedish firm Orexo AB to develop and market the treatment in 2004. (See BioWorld Today, Aug. 19, 2004.)
McAllister maintained a "sell" rating on Cephalon because of concerns about promotional practices and settlements with generic drug makers, but acknowledged that the premium price that London-based AstraZeneca plc intends to pay for MedImmune Inc., of Gaithersburg, Md., has made him "a little concerned." For the Cephalon rival MedImmune, AstraZeneca has agreed to pay a whopping $15.2 billion - which suggests Cephalon might be undervalued, too. (See BioWorld Today, April 24, 2007.)
Still, McAllister has no plans to change his rating. "If anything, this [BEMA Fentanyl data] works in my favor," he said. "More competition is never good."
Cephalon's stock (NASDAQ:CEPH) ended Wednesday at $75.30, up 21 cents.