Cephalon Submits Supplemental New Drug Application For FENTORA

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Cephalon has submitted a supplemental New Drug Application (sNDA) to FDA seeking approval to market FENTORA (fentanyl buccal tablet) [C-II] for the management of breakthrough pain in opioid tolerant patients with chronic pain conditions. Breakthrough pain is characterized by its rapid onset, moderate- to-severe intensity, and relatively short duration. According to a study published in the August 2006 issue of The Journal of Pain, up to 74 percent of patients with non-cancer chronic pain conditions treated for persistent pain, such as chronic low back and chronic neuropathic pain, will experience breakthrough pain. Currently FENTORA is approved for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent pain.

"The clinical trials supporting this submission mark the first time a pain medication has been evaluated as a treatment for breakthrough pain associated with serious chronic pain conditions other than cancer," said Dr. Lesley Russell, Executive Vice President, Worldwide Medical and Regulatory Operations. "We look forward to working with FDA to broaden the use of FENTORA to opioid tolerant patients with unresolved debilitating breakthrough pain."

The FENTORA sNDA includes data from three randomized, placebo-controlled clinical trials and one long-term open-label safety study with a total of 941 opioid tolerant patients. The patients in the FENTORA sNDA trials were treated for up to 18 months and had a broad range of underlying chronic pain conditions, including chronic low back and chronic neuropathic pain. In the randomized clinical trials, opioid tolerant patients with chronic pain treated with FENTORA experienced statistically significant improvements in relief from breakthrough pain with an onset and duration of relief similar to that seen in studies of FENTORA in patients with cancer pain. The FDA's typical review period for a sNDA is 10 to 12 months.

"Breakthrough pain appears to be highly prevalent in some populations with chronic non-cancer pain, and the commitment to use an opioid to manage chronic pain should be accompanied by an effort to assess and manage the breakthrough pain as well," said Dr. Russell Portenoy, Chairman, Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, in New York City, and a principal investigator in the FENTORA clinical trials. "New treatment options that specifically target breakthrough pain are welcome, and are likely to improve the clinician's ability to address this problem effectively."

About Breakthrough Pain

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Millions of Americans suffer from chronic pain, a condition that often consists of two distinct components: persistent pain, which is pain that is continuous throughout the day, and breakthrough pain, which is a transitory flare of moderate-to-severe pain in patients with otherwise managed persistent pain. Breakthrough pain can reach peak intensity in as little as three minutes and typically lasts for 30 to 60 minutes. It may occur during a specific activity, spontaneously with no apparent cause, or when the dose of the persistent pain medicine wears off.

About FENTORA

Approved in September 2006, FENTORA is the first tablet formulation of the opioid fentanyl and the first new medication approved for the management of breakthrough pain in opioid tolerant patients with cancer since 1998. Its proprietary OraVescent(R) drug delivery system was developed by Cephalon subsidiary CIMA LABS. FENTORA is covered by patents until 2019.

The sugar-free FENTORA tablet is placed between the cheek and gum above a rear molar tooth where it remains until it dissolves. When it comes into contact with saliva, FENTORA's delivery system generates a chemical reaction believed to optimize how well the tablet dissolves and how quickly the medicine passes across the lining of the upper check, or buccal mucosa. With FENTORA's drug delivery technology, approximately half of the medicine is absorbed directly across the lining of the upper cheek and into the bloodstream. Conventional short-acting oral opioids, often used to treat breakthrough pain, are swallowed and must first be absorbed in the gastrointestinal tract, which can take up to 30-45 minutes to reach effect.

In clinical trials, FENTORA was generally well tolerated. Most adverse events occurring with FENTORA are typical opioid side effects. The most serious adverse events associated with all opioids are respiratory depression (potentially leading to apnea or respiratory arrest), circulatory depression, hypotension, and shock. All patients should be followed for symptoms of respiratory depression. Opioid side effects should be expected and managed accordingly. The most common (greater or equal to 10 percent) adverse events observed in clinical trials of FENTORA in patients with cancer were nausea, vomiting, application site abnormalities, fatigue, anemia, dizziness, constipation, edema, asthenia, dehydration, and headache. In clinical trials in patients with other chronic pain conditions, the most common (greater or equal to 10 percent) adverse events were nausea, vomiting, back pain, dizziness, headache, and somnolence. Application site adverse events were reported in 12 percent of patients. Most side effects were mild to moderate in severity. No attempt was made to correct for concomitant use of around- the-clock opioids or cancer-related symptoms.

Post-marketing reports of serious adverse events, including deaths in patients treated with FENTORA, have been reported. Deaths occurred as a result of improper patient selection and/or improper dosing. FENTORA is contraindicated in the management of acute or postoperative pain including headache/migraine. Life-threatening respiratory depression could occur at any dose in patients not regularly taking around-the-clock opioids. The label for FENTORA is currently being updated to reflect these and other important safety considerations.

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