Ralfinamide fails in Serena study on NLBP patients

Newron Pharmaceuticals SpA, a research and development company focused on novel CNS and pain therapies, has announced that the topline top-line results of its Serena study, a phase-IIb/III study of ralfinamide in patients with at least moderate Neuropathic Low Back Pain (NLBP) failed to show any significant difference between ralfinamide and placebo.

The 12-week Serena study enrolled 411 patients with chronic NLBP of at least moderate severity and evaluated the safety and efficacy of two dose regimens of ralfinamide compared to placebo. Available results on the primary endpoint of the study, the change from baseline for the 11-point Likert Scale, did not detect any significant difference between ralfinamide and placebo. Ralfinamide was well tolerated, with no clinically significant differences from placebo on safety measures.

Further analyses of the additional endpoints (VAS, PGI, CGI etc) are currently ongoing and will be reviewed with Newron’s external advisors. Based on the multiple CNS effects seen in animal pharmacology models, and the excellent human safety data, Newron will decide how to proceed further with the compound.

Luca Benatti, Newron´s chief executive officer, commented, “We are extremely surprised and disappointed by the results, based on the statistically significant benefits shown in a phase II placebo-controlled trial, as well as the results from a large number of preclinical studies. We shall be working with our external advisors to make a complete assessment of the data prior to determining our next steps, including a review of our development resource needs going forward. We have a broad portfolio of products in various stages of development, addressing substantial market opportunities and this, combined with our existing cash resources and SEDA equity line, gives Newron continued potential for growth and value generation.”

In addition to ralfinamide, Newron has an advanced pipeline of innovative compounds, that include safinamide, currently in phase-III development for the treatment of Parkinson’s disease (add-on treatment for all stages of PD) together with Merck Serono; NW-3509, an novel treatment for schizophrenia expected to enter human trials later this year, and HF0220, a potential disease-modifying therapy for neurodegenerative disorders, currently in phase-II.

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FDA aprroves a new pain drug

Shares of Pozen Inc. surged more than 21% in the after hours trading session Friday after the U.S. Food and Drug Administration or FDA approved VIMOVO delayed-release tablets for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, and to decrease the risk of developing gastric ulcers in patients at risk of developing NSAID-associated gastric ulcers.

VIMOVO, co-developed by Pozen and UK-based drug maker AstraZeneca Plc is a fixed-dose combination of enteric-coated naproxen, a pain-relieving non-steroidal anti-inflammatory drug or NSAID, and immediate-release esomeprazole, a proton pump inhibitor or PPI.

The FDA approval was supported by data from a clinical development program, including results from the pivotal PN400-301 and PN400-302 studies, which showed patients taking VIMOVO experienced significantly fewer endoscopic gastric ulcers, compared to patients receiving enteric-coated naproxen.

Nearly 27 million US residents and 140 million people worldwide suffer from osteoarthritis, which is the most common form of arthritis. According to the company, half of osteoarthritis patients on chronic non-steroidal anti-inflammatory drugs therapy are at the risk of developing gastric ulcers associated with it.

Howard Hutchinson, M.D., Chief Medical Officer, AstraZeneca, said, “In a single pill, VIMOVO provides a proven pain reliever with a built-in PPI for arthritis patients at-risk for NSAID-associated gastric ulcers.”

In the PN400-301 and 302 studies, the primary end point was the cumulative incidence of gastric ulcers through six months. Patients received either VIMOVO or enteric-coated naproxen 500 mg, twice daily, in each of the trial, over a six-month treatment period.

Data from study PN400-301 showed a 4.1% incidence of gastric ulcers in patients taking VIMOVO, compared to 23.1% among patients taking enteric-coated naproxen. Study PN400-302 showed a 7.1% incidence of gastric ulcers among patients taking VIMOVO, compared to 24.3% with enteric-coated naproxen.

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New pain medications increase doctors’ options

With the development of pain clinics, the treatment of chronic pain has become a specialized field of medicine that includes injections, devices, procedures and, of course, drugs.

Some of the drugs are used for acute (temporary) pain as well as chronic (long-term) pain. Other drugs should only be used for acute pain.

In the emergency department, I get lots of experience prescribing drugs for acute pain. People seem to get injured every day and come to the hospital looking for some relief from their suffering.

When they do, I must keep in mind their entire list of medical problems, allergies and current medications when prescribing something for their pain. Sometimes it is hard to think of a drug that fills the bill, especially in people who have had trouble with previous pain medicines for whatever reason.

That is why I am always happy to learn of another drug to try in these situations. In fact, the Food and Drug Administration recently approved a new drug called tapentadol (Nucynta) for treatment of moderate to severe acute pain in patients 18 years or older.

Although it has some structural similarity to tramadol (Ultram), which is not classified as a controlled substance, tapentadol has been classified as a Schedule II controlled substance. This means that it is in the same class as narcotics like morphine, demerol, dilaudid and others.

Studies show tapentadol to be as effective in treating pain as moderate doses of morphine and oxycodone. However, more than one in 10 patients reported nausea, dizziness, vomiting, headache and/or sleepiness. Seizures, which have been a problem with tramadol, are a theoretical concern but have not been reported.

Tapentadol has a high potential for abuse and discontinuing the drug without tapering the dose has led to symptoms consistent with withdrawal.

There are also some drug interactions with other pain medicines, antidepressants and migraine headache drugs that will require careful attention by the prescriber. This also means that nobody should casually take someone else’s tapentadol. It is never a good idea to take a prescription drug dispensed for another person unless instructed to do so by an appropriate and well-informed healthcare professional.

Tapentadol should be used carefully in patients with liver disease since it is mainly broken down and removed from the body by the liver. It should not be used at all in patients with severe liver or kidney impairment. Also, after the first dose, doses higher than 600 mg per day are not recommended.

With all of the above information in mind, I polled some local pharmacies and found that some of them do not have the drug on hand yet. However, one pharmacy has filled a prescription for it already.

Unless there is no alternative, I have no plans of using this drug any time soon since I have lots of prescribing experience with several older drugs that can control acute pain. It is also expensive, at nearly $2 per pill. However, I think it is very important to know about new drugs that may benefit patients who might not be able to take the older, cheaper drugs for some reason.

Source : www.fwdailynews.com

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Long-used pain pills to carry new warnings

Propoxyphene, better known by long-used brand names Darvon and Darvocet, may stay on the market, but must carry a new, stronger version of the Food and Drug Administration's most serious warnings to consumers and physicians. Products containing propoxyphene, an opiate used to treat mild to moderate pain, will now carry more stringent warnings about the dangers of taking more than the recommended dose, the FDA announced today.

The agency also announced that it has ordered studies on the risk of dangerous cardiac side effects associated with Darvon and related pain medications, as well as on the extent of their use in the elderly -- a population for which propoxyphene is considered to be problematic and less effective than newer, safer drugs.

Propoxyphene's dangers most recently came to light in February 2006, when the group Public Citizen petitioned the FDA to remove the drug from the market. The FDA said today that while it may take further action against the pain drug after studies have been completed, it would allow its continued sale, with the strengthened "black-box" warnings.

The decision came as the agency also considers the advice of one of its own advisory panels, which recently recommended banning further sale of several other widely prescribed opiate pain medications -- those that include acetaminophen, among them Vicodin and Percocet.

Propoxyphene was found to have been associated with roughly 2,110 deaths in the United States between 1981 and 1999, and during the same period was found in autopsies to have been implicated in 5.6% of drug-related deaths in the U.S. Public Citizen had sued the FDA in June of last year for failing to rule on its 2006 petition, prompting the FDA to act this week.

Source : latimesblogs.latimes.com

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Panel Recommends Ban on 2 Popular Painkillers

A federal advisory panel voted narrowly on Tuesday to recommend a ban on Percocet and Vicodin, two of the most popular prescription painkillers in the world, because of their effects on the liver.

The two drugs combine a narcotic with acetaminophen, the ingredient found in popular over-the-counter products like Tylenol and Excedrin. High doses of acetaminophen are a leading cause of liver damage, and the panel noted that patients who take Percocet and Vicodin for long periods often need higher and higher doses to achieve the same effect.

Acetaminophen is combined with different narcotics in at least seven other prescription drugs, and all of these combination pills will be banned if the Food and Drug Administration heeds the advice of its experts. Vicodin and its generic equivalents alone are prescribed more than 100 million times a year in the United States.

Laureen Cassidy, a spokeswoman for Abbott Laboratories, which makes Vicodin, said, “The F.D.A. will make a final determination and Abbott will follow the agency’s guidance.”

The agency is not required to follow the recommendations of its advisory panels, but it usually does.

The panel’s 20-17 vote to recommend a ban on the combination drugs was one of 11 it took at a meeting called to advise the F.D.A. on problems arising from the extraordinary popularity of acetaminophen. In 2005, American consumers bought 28 billion doses of products containing the ingredient.

While the medicine is effective in treating headaches and reducing fevers, even recommended doses can cause liver damage in some people. And more than 400 people die and 42,000 are hospitalized every year in the United States from overdoses.

In hopes of reducing some of these accidents, the committee voted 24 to 13 to recommend that the F.D.A. reduce the highest allowed dose of acetaminophen in over-the-counter pills like Tylenol to 325 milligrams, from 500. And members voted 21 to 16 to reduce the maximum daily dosage to less than 4,000 milligrams.

But they voted 20 to 17 against limiting the number of pills allowed in each bottle, with members saying such a limit would probably have little effect and could hurt rural and poor patients. Bottles of 1,000 pills are often sold at discount chains.

“We have no data to show that people who overdose shop at Costco,” said Dr. Edward Covington, a panel member from the Cleveland Clinic Foundation.

Dr. Lewis S. Nelson, a toxicologist from the New York University School of Medicine who served as the panel’s acting chairman, said experts had been warning of the dangers of combination painkillers like Percocet, which is made by Endo Pharmaceuticals, and Vicodin for years.

Still, the recommendation is likely to come as a shock to many patients, who may be unaware of the dangers of high doses of acetaminophen — even if they know the drugs contain the ingredient.

Some doctors already avoid prescribing pills that combine acetaminophen with narcotics like oxycodone (found in Percocet) and hydrocodone (in Vicodin).

“It ties the doctor’s hands when you put the two drugs together,” said Dr. Scott M. Fishman, a professor of anesthesiology at the University of California, Davis, and a former president of the American Academy of Pain Medicine. “There’s no reason you can’t get the same effect by using them separately.”

Dr. Fisher said the combinations were prescribed so often for the sake of convenience, but added, “When you’re using controlled substances, you want to err on the side of safety rather than convenience.”

Still, some doctors predicted that the recommendation would put extra burdens on physicians and patients.

“More people will be suffering from pain,” said Dr. Sean Mackey, chief of pain management at Stanford University Medical School. “More people will be seeing their doctors more frequently and running up health care costs.”

In a statement, Johnson & Johnson, Tylenol’s maker, said it “strongly disagrees” with the proposed restrictions on acetaminophen, adding that they would be likely to “lead to more serious adverse events as consumers shift to other over-the-counter products,” like Advil and aspirin.

Linda A. Suydam, president of the Consumer Healthcare Products Association, said the committee had ignored studies showing that doses sold by her members — two pills of 500 milligrams, up to four times a day — were safe. “I think this is a very effective dose and one needed for individuals who experience chronic pain,” she said.

The committee also turned its attention to over-the-counter children’s medicines containing acetaminophen, voting 36 to 1 to limit them to a single formulation. Right now the liquids are sold in two different concentrations, leading to confusion among doctors and parents.

“I don’t think it’s safe to have two formulations out there,” said Dr. Nelson, the acting chairman.

The members were divided over which formula to recommend, the concentrated or the less concentrated one. F.D.A. officials suggested that they would likely settle on the less concentrated formula so that if parents make a mistake, they would be less likely to overdose.

Acetaminophen is included in a vast array of over-the-counter cough and cold products, including Nyquil, Excedrin and many others. A small share of accidental poisonings result when people take two or more of these combination products without understanding the risk.

The F.D.A. asked the committee whether it should ban combination products that include acetaminophen. The vote was 24 to 13 against such a ban, with many members saying consumers saw the products as valuable.

“Based on the data provided, the combination O.T.C. medications really contributed very little to overall poisonings,” said Dr. Osemwota A. Omoigui, a panel member from the Los Angeles Pain Clinic.

A 2005 study found that most poisonings resulted from patients’ taking Vicodin and similar products that combine a narcotic with acetaminophen.

“I think this is the one place where we can engineer in safety,” said Dr. Judith M. Kramer, a panel member and an associate professor of medicine from Duke University Medical Center who voted to ban the combination prescription medicines. “We’re here because there are inadvertent overdoses that are fatal, and this is our one opportunity to have a big impact.”

Consumers need to be better educated about the risks of popular medicines, most panel members agreed.

“If you keep track of what you’re taking, none of this is an issue for you,” Dr. Jan Engle, a panel member and head of the Department of Pharmacy Practice at the University of Illinois in Chicago, said in an interview after the meeting.

Source : www.nytimes.com

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