[Wing42]

From Medical News Today ( http://www.medicalnewstoday.com/ ). It is a press release from the big-pharm company Cephalon

Cephalon Announces Positive Results From A Pivotal Study Of FENTORA In Opioid-tolerant Patients With Non-cancer Breakthrough Pain

17 Aug 2007

Cephalon, Inc. (Nasdaq: CEPH) today announced positive results from a 12-week, Phase 3 clinical trial of FENTORA(R) (fentanyl buccal tablet) [C-II] in patients with breakthrough pain associated with a broad range of chronic non-cancer pain conditions. The study achieved statistical significance on the primary endpoint. Results across the 12 weeks of treatment showed both statistically significant and clinically relevant outcomes for patients with breakthrough pain who were already receiving and who were tolerant to opioid therapy for their underlying persistent pain. FENTORA is approved only 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 cancer pain.

"We are excited to complete our Phase 3 program with this third and final controlled study. These data show similar positive outcomes as those with FENTORA in treating breakthrough pain in opioid-tolerant patients with cancer, chronic neuropathic pain, and chronic low-back pain," said Dr. Lesley Russell, Executive Vice President, Worldwide Medical and Regulatory Operations. "We plan to submit these data to the Food and Drug Administration in the fourth quarter as part of our supplemental New Drug Application."

About the Study

The double-blind, placebo-controlled, variable dose Phase 3 trial included 148 patients. The primary endpoint was the Sum of Pain Intensity Differences from five to 60 minutes (SPID(60)) as assessed after 12 weeks of treatment. SPID(60) is a measure that assesses analgesic efficacy of a pain medication over the first 60 minutes after treatment. Patients treated with FENTORA showed a statistically significant improvement on the primary endpoint (p<0.0001) compared with placebo. FENTORA was generally well tolerated by the study participants with side effects consistent with those in the currently approved label. The company plans to present the data at a major medical meeting in the future.

About Breakthrough Pain

Breakthrough pain is a component of chronic pain that is characterized by its rapid onset, moderate to severe intensity, and relatively short duration. Breakthrough pain has an average onset of three to five minutes and typically lasts 30 to 60 minutes.

About FENTORA

FENTORA is indicated only for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy, as described below in the FENTORA label, for their underlying persistent cancer pain. FENTORA incorporates a drug delivery system that generates transient changes in pH, which may optimize how well the tablet dissolves and how quickly the medicine passes across the lining of the cheek, or buccal mucosa. 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. The most common (greater than or equal to 10 percent) adverse events observed in FENTORA cancer clinical trials were nausea, dizziness, vomiting, fatigue, headache, constipation, anemia, somnolence, and peripheral edema. Most adverse events were mild to moderate in severity. No attempt was made to correct for concomitant use of around-the-clock opioids or cancer-related symptoms. In addition, application site reactions were reported in nine percent of patients, tended to occur early on treatment, and resulted in treatment discontinuation in only two percent of patients.

PHYSICIANS AND OTHER HEALTHCARE PROVIDERS MUST BECOME FAMILIAR WITH THE IMPORTANT WARNINGS IN THIS LABEL.

FENTORA contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. FENTORA can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing FENTORA in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Schedule II opioid substances which include morphine, oxycodone, hydromorphone, oxymorphone, and methadone have the highest potential for abuse and risk of fatal overdose due to respiratory depression.

FENTORA is indicated only 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 cancer pain. Patients considered opioid tolerant are those who are taking at least 60 mg of oral morphine/day, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer. Because life-threatening respiratory depression could occur at any dose in opioid non-tolerant patients, FENTORA is contraindicated in the management of acute or postoperative pain. This product is not indicated for use in opioid nontolerant patients.

Patients and their caregivers must be instructed that FENTORA contains a medicine in an amount which can be fatal to a child. Patients and their caregivers must be instructed to keep all tablets out of the reach of children. (See Information for Patients and Caregivers for disposal instructions.)

Due to the higher bioavailability of fentanyl in FENTORA, when converting patients from other oral fentanyl products, including oral transmucosal fentanyl citrate (OTFC and Actiq(R)), to FENTORA, do not substitute FENTORA on a mcg per mcg basis. Adjust doses as appropriate. (See DOSAGE AND ADMINISTRATION.)

FENTORA is intended to be used only in the care of opioid tolerant cancer patients and only by healthcare professionals who are knowledgeable of and skilled in the use of Schedule II opioids to treat cancer pain.

The concomitant use of FENTORA with strong and moderate cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression.

Full prescribing information about FENTORA, including boxed warning, is available from http://www.FENTORA.com.

About Cephalon, Inc.

Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and marketing of innovative products in four core therapeutic areas: central nervous system, pain, oncology and addiction. Cephalon has delivered a seven-year compound annual growth rate (CAGR) through 2006 greater than 75 percent and 2006 revenue of $1.760 billion. A member of the Fortune 1000, Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company's headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota. Cephalon's European headquarters are located in Maisons-Alfort, France.

The company's proprietary products in the United States include: PROVIGIL(R) (modafinil) Tablets [C-IV], FENTORA, TRISENOX(R) (arsenic trioxide) injection, VIVITROL(R) (naltrexone for extended-release injectable suspension), GABITRIL(R) (tiagabine hydrochloride), NUVIGIL(TM) (armodafinil) Tablets [C-IV] and ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II]. The company also markets numerous products internationally.

In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Cephalon's current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs; development of potential pharmaceutical products; interpretation of clinical results including the FENTORA clinical trials discussed herein; prospects for regulatory approval, including the timing of an sNDA filing for FENTORA; manufacturing development and capabilities; market prospects for its products; sales, adjusted net income and basic adjusted income per common share guidance for the third quarter and full-year 2007; and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as "anticipate," "estimate," "expect," "project," "intend," "plan," "believe" or other words and terms of similar meaning. Cephalon's performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions affecting the biotechnology and pharmaceutical industries as well as more specific risks and uncertainties facing Cephalon such as those set forth in its reports on Form 8-K, 10-Q and 10-K filed with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward- looking statements. Furthermore, Cephalon does not intend to update publicly any forward-looking statement, except as required by law. The Private Securities Litigation Reform Act of 1995 permits this discussion.

Cephalon, Inc.

http://www.cephalon.com Article URL: http://www.medicalnewstoday.com/articles/79919.php

Main News Category: Pain / Anesthetics
Also Appears In: Clinical Trials / Drug Trials,

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[dahlek]

think that ingesting Fentanyl might be a good way for some. But a phase 3 clinical trial of less than 150 people? And for only 12 weeks - those are my concerns.

That it has not gotten FDA approval yet, even only a very small clinical trial is encouraging because of the aspects mentioned above and that it could be an effective way to help people. But, the 'documentation' for neurontin for PN [actually far less by way of clinical work] when it was pushed 5 years ago, was not only poor it was inexcusable and docs bought it.

I certainly wish that the 90%of the medications and treatments we are helped by get OFF the 'off-label' use menus in our lifetimes.

The good thing is that they've gotten beyond the MOUSE MODEL stages tho?

David, I hope you have a whole lot more pain-free times and continue to improve! Good thoughts to you always - j

[Wing42]

Originally Posted by dahlek

think that ingesting Fentanyl might be a good way for some. But a phase 3 clinical trial of less than 150 people? And for only 12 weeks - those are my concerns.

That it has not gotten FDA approval yet, even only a very small clinical trial is encouraging because of the aspects mentioned above and that it could be an effective way to help people. But, the 'documentation' for neurontin for PN [actually far less by way of clinical work] when it was pushed 5 years ago, was not only poor it was inexcusable and docs bought it.

I certainly wish that the 90%of the medications and treatments we are helped by get OFF the 'off-label' use menus in our lifetimes.

The good thing is that they've gotten beyond the MOUSE MODEL stages tho?

David, I hope you have a whole lot more pain-free times and continue to improve! Good thoughts to you always - j

Thanks for the kind words.

Modern medicine is as unscientific as it is scientific. Drug trials are for short periods, "bad" results are not included, and the real-life norm of people taking many different drugs would disqualify them as trial subjects. Also, the very ill, people with weak kidneys, damaged livers, the very old are excluded. Instead of independent testing, we have drug companies running their own trials, or paying others to do testing for them. The conflict of interest is blatant.

We need to be careful and responsible for ourselves, question doctors (respectfully) to understand why that particular drug is prescribed and expected side effects.

I'm not at all advocating the use of any medication, but for people at the end of their rope, this is another alternative.

[Kathi49]

Thanks for the info. Wing.

I am about ready to try the Duragesic patch 12mcg. But remember...I have spinal disorders too. My spinal PM thought that this would be a good way to go since I cannot tolerate a lot of meds. Anyway, I did question him about it thoroughly. The insert is enough to scare the heck out of anyone. But he told me that the 12mcg is pretty much equivalent to two Vicodin a day. Which is fine with me since it seems I have always either taken Norco or Vicodin...one to two a day...never any more than that. For me, the opiates help with the neuropathic pain and/or PN. It is the anti-convulsant types that really mess me up and increase burning...Neurontin being one of them. Lyrica caused major muscle pain and Depakote just sent me into a tizzy. And Elavil and Cymbalta just made me sicker than a dog. I do take Klonopin .5 once a day and it has helped considerably. I know, I know...it is benzo. But I had a list once of every med I have ever tried. And the only combination that made me functional again was Vicodin and Klonopin. I DID try supplements once and I will say since I wasn't deficient in anything they didn't do a thing. Again, my PN is more of a spinal thing and believe me, when you have osteo compressing nerve roots no amount of supplements will fix that! So, I DO have to combat it with meds and/or injections.

Anyway, I am going to wait for cooler temps before I try this patch. If it works well, I will post back. I have talked to a lot of people who just swear by it. But it all remains to be seen.

[LizaJane]

What makes Fentanyl better than other opioids? For breath-thru pain that requires an opiate, there's quick acting Oxycodone IR, cheap and off patent.

I can't see why you cant' put it under your tongue if you want; afterall, you could crush it and sniff it if you were so inclined.

[Dakota]

I honestly don't know what would make a fentanyl pill better than another opioid. The patch delivery system is generally better than oral drugs as it keeps the level constant and this means you usually can get by on a lower overall dose. It's true that drugs are not tested well. You know, everyone is always so afraid of narcotics, but they have been around for centuries and at least we know what they do. But drugs like Neurontin and Lyrica.... we have no idea what the long term effects are. I do take Lyrica in addition to the fentanyl patch because I haven't found another way to get tolerable relief. But I'm not happy about it. I'm getting ready to make an all out effort to loose weight and see if I can't tolerate some exercise of some sort -- I'm going to try water aerobics again and maybe Yoga.

[Kathi49]

Dakota,

You are right and I was speaking of the patch too...not the pill. The way it was explained to me is that it would be a steady and consistent dose without the peaks and valleys from taking other forms of opoids. AND...I was told IF there was breakthrough pain I could still take a Vicodin. The dose my PM prescribed was 12mcg...a newer patch...not the standard 25mcg. Not only that but there are so many different forms of neuropathic pain that one type of med may or may not work or even touch the pain. I know Neurontin did nothing for my cervicogenic headaches and actually made me worse along with increasing burning sensations. If I can help it at all, I will NEVER go back to Neurontin or Lyrica. I went that route for 3 years and it was awful!
I can't tolerate the AD's either...been there and done that too. So, when my spinal PM mentioned the Duragesic patch, I am willing to give it a try. I just want to wait until the cooler months when I do. But as far as I understand it, you have to be opoid tolerant. I questioned this because I do NOT take more than one Vicodin a day...sometimes maybe two when the pain is bad. But my PM assured me that I have been on it long enough even though I don't take a lot. And the nice thing about the patch is that it goes directly into the bloodstream and bypasses the liver. It would be really nice if this worked for me and I could pitch the Vicodin and eventually taper off the Klonopin. I have talked with a lot of people at the other "site" and from what they have said...the patch gave them a great deal of relief. But again, it remains to be seen.