Nalmefene used  in the management of alcohol dependence

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La farmacéutica danesa Lundbeck ha desarrollado un nuevo medicamento para adictos al alcohol que, según los primeros resultados de los ensayos clínicos presentados en el último Congreso Europeo de Psiquiatría celebrado en Praga (República Checa), consigue reducir el consumo diario en un 60 por ciento.

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El compuesto está basado en un antagonista opioide llamado nalmefene y funciona bloqueando los mecanismos del cerebro responsables del efecto de placer que proporciona el alcohol.

En virtud de estos primeros resultados, la farmacéutica ya ha solicitado a la Agencia Europea de Medicamentos (EMA, en sus siglas en inglés) la licencia de comercialización del fármaco pese a que todavía debe demostrar los efectos más a largo plazo del medicamento.

Lundbeck ha licenciado el fármaco a partir de la Biotie Therapeutics y realizó ensayos clínicos con nalmefene para el tratamiento de la dependencia al alcohol. En 2011 se presentó una solicitud de formulación farmaceútica de la droga denominada Selincro a la Agencia Europea de Medicamentos.

Namelfene se diferencia del resto de los fármacos ya que está disponible en presentación de comprimidos que se toman según las necesidades del paciente, mientras que el resto de fármacos existentes deben administrarse de forma continúa durante periodos largos de tiempo.

En anteriores estudios, nalmefene ha demostrado su capacidad para limitar significativamente la ingesta media de alcohol y el número de días con un consumo por encima de cinco unidades de alcohol. Esto significa una importante reducción del riesgo de desarrollar enfermedades causadas por el alcoholismo como son las patologías cardiovasculares, algunos tipos de cáncer y la cirrosis hepática.

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Desarrollan un fármaco que ayuda a los alcohólicos a beber menos

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6 Marzo 2012 - Madrid - Ep - http://www.larazon.es/noticia/3313-desarrollan-un-farmaco-que-ayuda-a-los-alcoholicos-a-beber-menos

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Actualmente, el tratamiento estándar para la dependencia al alcohol está basado en la terapia psicológica y también hay fármacos disponibles para ayudar a los pacientes que intentan dejar el hábito.

Por ejemplo, hay algunos que ayudan a evitar una recaída en el consumo de alcohol durante los períodos de abstinencia, medicamentos que causan náusea y malestar cuando se consume alcohol o terapias para aliviar los síntomas de abstinencia, que incluyen ansiedad e insomnio.

Pero, de momento, no existían tratamientos para reducir el ansia que sienten los alcohólicos para consumir la bebida y, de hecho, es por eso por lo que estos pacientes experimentan altas tasas de recaída cuando intentan dejar de beber.

Para evaluar la eficacia de este compuesto, se pusieron en marcha tres ensayos clínicos que incluían a un total de 1.997 pacientes de clínicas en Austria, Finlandia, Alemania y Suecia. Los pacientes debían tomar una pastilla cuando la necesitaran, es decir, cuando se sintieran en riesgo de necesitar una bebida alcohólica.

Paralelamente, se les ofreció asesoría médica y psicológica para motivarlos y ayudarlos a adherirse a la terapia pero, en ningún momento, no se les impuso a un objetivo específico de abstinencia.

Durante los seis meses de tratamiento, los resultados mostraron que los participantes lograron reducir su consumo diario en 66 por ciento, comparado con el grupo que tomó placebo.

De este modo, la cantidad de consumo de alcohol consumido diariamente se redujo de 84 gramos al día (el equivalente de una botella de vino) a 30 gramos diarios (un vaso grande de vino).

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BEBIAN MENOS CANTIDAD, Y MENOS DIAS

Los participantes que recibieron el tratamiento también lograron reducir el número de días que bebían en exceso (más de 60 gramos de alcohol, en hombres, o 40 gramos en mujeres) de 19 a 7 días al mes en promedio. Además, los beneficios de dicho fármaco lograron mantenerse durante un año.

Los efectos secundarios más frecuentes fueron mareos, náuseas, fatiga, sudor excesivo, trastornos de sueño, incluido insomio, vómito

y síntomas similares a los del resfriado.

"La gente que participó en estos ensayos clínicos tenía un problema real de dependencia al alcohol", según ha reconocido a la BBC el doctor David Collier de la Universidad Queen Mary en Londres, uno de los investigadores del estudio.

Además, según ha explicado en declaraciones recogidas por Europa Press, "la mayoría nunca había pedido ayuda para su adicción y algunos habían fracasado con sus estrategias de abstinencia para dejar de beber".

"Basados en la experiencia que tuvimos con estos ensayos, la reducción del consumo de alcohol a niveles seguros puede ser un objetivo realista y práctico para la gente que tiene una dependencia al alcohol, y esto puede traer muchos beneficios a corto y largo plazo para su salud", ha señalado el investigador.

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Nalmefene es un antagonista de los receptores opiáceos. El compuesto actúa bloqueando el mecanismo en el cerebro que puede causar una continua y descontrolada ingesta de alcohol. Así que es un nuevo principio activo para el tratamiento de la dependencia alcohólica cuyo fin es que el paciente pueda controlar su ansia por beber y limitar la ingesta de alcohol.

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http://www.larazon.es/noticia/3313-desarrollan-un-farmaco-que-ayuda-a-los-alcoholicos-a-beber-menos

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BORRACHOS: NEGOCIO REDONDO

La droga puede tener máximos de venta de $ 55 millones, suponiendo que un 10% de pacientes alcohólicos diagnosticados en Europa lo tomaran, aunque los ingresos podrían alcanzar los $ 300 millones, estiman analistas del Grupo Jefferies. Las mayores ventas requerirían un acuerdo para vender el medicamento a los médicos generales o mediante promoción gubernamental en los países que buscan mejorar la salud pública.

Lundbeck formará una sociedad de comercialización una vez que el etiquetado de nalmefene se halla aprobado en la Agencia Europea del Medicamento. Nalmefene no será vendida en los EE.UU., donde estaría protegido de la competencia de los genéricos por sólo cinco años, en comparación con 10 años de protección en Europa, apuntó el Director Financiero de Lundbeck, Anders Gotzsche.

Lundbeck Anti-Binge Drinking Drug Helps Cut Intake by 66%

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H. Lundbeck A/S (LUN), the Nordic region’s second-largest drugmaker, said its anti-alcoholism treatment nalmefene helped patients cut consumption by an average of 66 percent in three clinical trials.

Results of the final stage of clinical trials showed nalmefene helped curb drinking more than a placebo and medical advice, Lundbeck said in a presentation at a medical meeting in Prague today. Nalmefene users reported a 64 percent to 79 percent drop in total alcohol intake, compared with 49 percent to 64 percent for those on placebo, Copenhagen-based Lundbeck said.

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By Makiko Kitamura - Mar 5, 2012

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Heavy drinking is Europe’s second-largest risk factor for poor health. Lundbeck plans to offer nalmefene as a treatment option to those who suffer from alcohol dependency and are turned off by abstinence, which is advocated by most experts, said Anders Gersel Pedersen, head of Lundbeck’s research and development. About 70 percent of patients who enrolled in the clinical trials for nalmefene had never received treatment, Pedersen said in a telephone interview.

“It changes the whole paradigm around the conversation about alcohol use between the physician and the patient,” he said.

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Awaiting Approval

Lundbeck submitted nalmefene, which may become the first new medicine sold to treat heavy drinking in more than 15 years, to the European Medicines Agency in December based on the research. A decision on the drug from the European regulator probably will come in the beginning of next year, Pedersen said.

Lundbeck fell 0.7 percent to 117.10 kroner in Copenhagen. Shares of Turku, Finland-based Biotie Therapies Oyj (BTH1V), which licensed nalmefene to Lundbeck, rose 2 percent to 52 euro cents in Helsinki. If the product is cleared, Biotie may receive as much as 84 million euros ($111 million) in payments from Lundbeck in addition to royalties on sales.

Patients taking nalmefene had high withdrawal rate in one of the three late-stage studies, mostly because of adverse events, Danske Markets analysts attending the Prague meeting wrote today in a note to investors. In the six-month Esense 1 trial, only 142 of 302 patients on the drug completed the study, compared with 205 of 296 patients taking placebo, the analysts said. The most frequent adverse events were dizziness, insomnia and nausea, Lundbeck said.

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Heavy Drinking Days

Those who stayed on the medication reported 63 percent fewer heavy drinking days and a 64 percent reduction in total alcohol consumption, the analysts wrote.

“This is quite a substantial difference,” they said.

While the differences between drinkers taking nalmefene and those getting a placebo were statistically significant, the results didn’t show a huge numerical difference, Jefferies International Ltd. analysts led by Peter Welford wrote in a note to investors today.

Patients who received a placebo and medical advice had a 50 percent reduction in heavy drinking days and total alcohol consumption in the Esense 1 trial, according to Lundbeck. In the six-month Esense 2 study, nalmefene users cut their heavy drinking days by 65 percent, compared with 61 percent in the placebo group. Total alcohol consumption fell 68 percent among those taking the drug, compared with a 63 percent decline for the placebo group.

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Placebo Effect

“This should be as expected given the medical advice available to all patients in the trials, and perhaps illustrates an important placebo-effect of a treatment” such as this “being made commercially available,” Welford and his colleagues wrote. “Nevertheless, this could complicate regulatory discussions.”

A third study, dubbed Sense, followed patients for 12 months and found nalmefene users had about an 80 percent reduction in both heavy drinking days and total alcohol intake, compared with 60 percent and 64 percent declines, respectively, in the placebo group, Lundbeck said.

Lundbeck is targeting Europe for nalmefene, where annual per capita consumption, at 12.18 liters (3.2 gallons), is double the global average and 40 percent higher than in the Americas, according to the World Health Organization. The drug will be marketed under the name Selincro.

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Alcohol Deaths

Alcohol abuse results in 2.5 million deaths each year, more than those caused by AIDS or tuberculosis, according to the Geneva-based WHO. The highest proportion of alcohol-related mortality is in Russia and neighboring countries, where every fifth death results from alcohol abuse.

“This is a potential revolution,” said David Nutt, professor of neuropsychopharmacology at Imperial College London, said in an interview before the study results were released. “Some people, like Alcoholics Anonymous, will be completely against it. But others will welcome it as a way to control their drinking.”

Nutt calls nalmefene a “drinking regulator” that would be “cheaper than getting drunk.” He has received grants or fees for consulting or speaking from drugmakers involved in addiction treatment including Lundbeck, though he didn’t play a role in any research on nalmefene.

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Peak Sales

The drug may have peak sales of $55 million, assuming 10 percent of diagnosed European patients take it, though revenue could reach $300 million, the Jefferies analysts estimated. Higher sales would require a partnership to sell the drug to general practitioners, or promotional support from governments seeking to improve public health, the analysts said.

Lundbeck is aiming to form a marketing partnership once the labeling of nalmefene has been defined with the European Medicines Agency, Pedersen said. Nalmefene won’t be sold in the U.S., where it would be protected from generic competition for only five years, compared with 10 years in Europe, Lundbeck Chief Financial Officer Anders Gotzsche said in a November interview.

Nalmefene works by blocking brain signals that make activities such as sex and drinking feel good. Patients on the medicine can continue drinking, an approach that divides alcohol treatment experts because many advocate abstinence.

Existing therapies include the generic drug Antabuse, also known as disulfiram, and Forest Laboratories Inc. (FRX)’s Campral and are generally used to help patients who have abstained from resuming drinking. Antabuse causes illness when alcohol is consumed, while Campral eases symptoms of withdrawal, such as anxiety and insomnia.

Lundbeck’s biggest seller is the antidepressant Lexapro, sold outside the U.S. as Cipralex. The drug generated 8.5 billion kroner ($1.5 billion) in worldwide sales last year and 581 million kroner in the U.S., where the patent expires in 2012.

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Nalmefene (Revex) used primarily in the management of alcohol dependence

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Nalmefene (Revex) is an opioid receptor antagonist developed in the early 1970s,[1] and used primarily in the management of alcohol dependence, and also has been investigated for the treatment of other addictions such as pathological gambling and addiction to shopping.

Nalmefene is an opiate derivative similar in both structure and activity to the opiate antagonist naltrexone. Advantages of nalmefene relative to naltrexone include longer half-life, greater oral bioavailability and no observed dose-dependent liver toxicity. As with other drugs of this type, nalmefene can precipitate acute withdrawal symptoms in patients who are dependent on opioid drugs, or more rarely when used post-operatively to counteract the effects of strong opioids used in surgery.

Nalmefene differs from naltrexone by substitution of the ketone group at the 6-position of naltrexone with a methylene (CH2) group, which considerably increases binding affinity to the μ-opioid receptor. Nalmefene also has high affinity for the other opioid receptors, and is known as a "universal antagonist" for its ability to block all three.

In clinical trials using this drug, doses used for treating alcoholism were in the range of 20-80 mg per day, orally.[2] The doses tested for treating pathological gambling were between 25-100 mg per day.[3] In both trials, there was little difference in efficacy between the lower and higher dosage regimes, and the lower dose (20 and 25 mg, respectively) was the best tolerated, with similar therapeutic efficacy to the higher doses and less side effects. Nalmefene is thus around twice as potent as naltrexone when used for the treatment of addictions.

Intravenous doses of nalmefene at between 0.5 to 1 milligram have been shown effective at counteracting the respiratory depression produced by opiate overdose [4], although this is not the usual application for this drug as naloxone is less expensive.

Doses of nalmefene greater than 1.5 mg do not appear to give any greater benefit in this application. Nalmefene's longer half-life might however make it useful for treating overdose involving longer acting opioids such as methadone, as it would require less frequent dosing and hence reduce the likelihood of renarcotization as the antagonist wears off.

Nalmefene is extensively metabolised in the liver, mainly by conjugation with glucuronic acid and also by N-dealkylation. Less than 5% of the dose is excreted unchanged. The glucuronide metabolite is entirely inactive, while the N-dealkylated metabolite has minimal pharmacological activity.

Lundbeck has licensed the drug from Biotie Therapeutics and performed clinical trials with nalmefene for treatment of alcohol-dependence.[5] In 2011 they submitted an application for their drug termed Selincro to the European Medicines Agency.[6]

Nalmefene - Wikipedia, the free encyclopedia

en.wikipedia.org/wiki/Nalmefene -

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