Merck-Cardiome heart rhythm drug meets study goals

Merck & Co. and Cardiome Pharma Corp. said Friday that their drug candidate Brinavess met its goal in a late-stage clinical study, as it was better at restoring a steady heartbeat than an older drug use for the same purpose.

The trial compared Brinavess to the standard drug, amiodarone, as a treatment for atrial fibrillation. Atrial fibrillation is a condition in which the upper chambers of the heart beat rapidly and ineffectively. Merck and Cardiome said more than half the patients treated with Brinavess had a normal heart rhythm within 90 minutes, compared to about 5 percent of the amiodarone patients.

The companies said 51.7 percent of Brinavess patients had a normal heart rhythm within that time, and the median time to normal heart rhythm was 11 minutes. They said 5.2 percent of the patients who were treated with amiodarone met that goal. After 90 minutes, 53.4 percent of the Brinavess patients had no symptoms, compared to 32.8 percent of the amiodarone group.

Brinavess is an intravenous version of vernakalant, a drug Merck and Cardiome have been developing together. The companies have filed for approval in the U.S. and the European Union, and they are also working on an oral form of the drug. If approved, Brinavess would compete with Sanofi-Aventis' drug Multaq, which was approved in 2009.

A total of 232 patients were treated in the study, and Merck and Cardiome said the Brinavess patients also had a greater quality of life improvement based on a survey. The most common side effects of Brinavess were a bad taste in the mouth, coughing, sneezing, atrial fibrillation, nausea, dizziness, and high blood pressure.

Results from the trial were presented at a Heart Rhythm Society meeting in Denver.

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Merck Buys Rights to Potential Chronic Lung Drug

Drugmaker Merck & Co. said Monday it has bought rights to help market what would be the first anti-inflammatory pill for a chronic lung condition, just a few days after European regulators recommended approval there.

The deal gives Merck rights to jointly market Daxas, made by Swiss drugmaker Nycomed, for chronic obstructive pulmonary disease in Canada and several European countries. Merck, based in Whitehouse Station, N.J., also received an exclusive distribution deal for the United Kingdom.

If approved, Daxas would be the first drug in a new class of treatments for chronic obstructive pulmonary disease, which includes bronchitis and emphysema.

However, U.S. regulators have recommended against its approval. Final decisions in the U.S. and Europe are still pending.

Daxas, a pill taken once a day, blocks an enzyme involved in the lung disorder and in related inflammatory diseases. Patients now generally take inhaled medicines including corticosteroids, which reduce inflammation, and bronchodilators, which open up airway passages in the lungs to ease breathing.

Under the deal, privately owned Nycomed will receive an undisclosed upfront fee and could get additional payments for meeting development and sales milestones.

If Daxas is approved, Merck and Nycomed will co-promote it in France, Germany, Italy, Spain, Portugal and Canada, while Merck will sell it exclusively in the United Kingdom.

Nycomed, based in Zurich, will make and distribute the product. It sells brand-name medicines for respiratory, inflammatory and gastrointestinal diseases, osteoporosis and pain, plus some over-the-counter products.

Forest Laboratories Inc. has U.S. rights to sell Daxas, for which it paid Nycomed $100 million.

Earlier this month, a panel of Food and Drug Administration lung experts voted 10-5 against approving Daxas, known chemically as roflumilast, because of concerns about potentially dangerous side effects. In a study comparing Daxas with another drug, problems including suicide, cancer and weight loss were more common among the patients receiving Daxas.

However, the panel voted 9-6 that Daxas appeared effective. An FDA decision is expected by mid-May.

Last Friday, the European Medicines Agency's Committee for Medicinal Products for Human Use recommended approval of Daxas for EU countries.

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Migraine Patients to Wait for Triptan Alternative

Scandinavian researchers writing in The Lancet gave a warm review to an investigational drug for migraine, but patients in the United States, at least, will have a wait before it reaches them.

Merck manufactures the drug, called telcagepant, and was initially expected to seek approval from the U.S. Food and Drug Administration last year.

An online Lancet review by researchers from Sweden and Norway touted telcagepant as holding out hope for migraine patients with acute attacks that fail to respond to migraine medications known as triptan drugs, such as Zomig and Imitrex. One major concern of these drugs has been their tendency to cause narrowing of the blood vessels, a process known as vasoconstriction.

"Telcagepant does not cause vasoconstriction, a major limitation in the use of triptans," wrote Dr. Lars Edvinsson of University Hospital in Lund, Sweden, and Dr. Mattias Linde of Norwegian University of Science and Technology in Trondheim.

"Telcagepant might provide hope for those who have a poor response to, or are unable to use, older drugs."

But elevations in certain liver enzymes among some telcagepant trial participants caused Merck to hold back in the U.S., fearing an application would be rejected. In September, the company announced that it was meeting with FDA officials to discuss how to proceed.

As a result, a Merck spokeswoman told MedPage Today, the company will sponsor another clinical safety study to begin this year. She said the trial was still being designed, and the protocol would be posted to the Clinicaltrials.gov Web site about the time enrollment begins.

No other information, such as the projected completion date, is available at this time, the spokeswoman said.

The group of drugs called CGRP receptor antagonists, to which telcagepant belongs, represents a new front in the war on migraine, as Edvinsson and Linde explained.

The receptor appears throughout the nervous system, both central and peripheral, and researchers believe it helps regulate vascular tone, pain signaling, motor function, and other activities with neurologic components.

A variety of studies have implicated it specifically in migraine, notably findings that CGRP levels rise in cranial blood and saliva during attacks.

But the two researchers said the clinical findings with telcagepant were marred by the liver abnormalities, which they called "slightly disturbing."

A 12-week phase IIa trial was stopped a year ago when some patients showed these liver problems toward the end of the study.

Edvinsson and Linde also noted that relatively high doses of the drug are needed to reduce migraines -- more than 100 mg, compared with 5 mg for zolmitriptan.

"Outstanding questions include whether CGRP receptor antagonists can be combined with triptans to give more effective therapy and whether they will be of value in patients who do not respond to a triptan," the researchers wrote.

"Additionally, effectiveness of triptans in children has not been proven, a group that might benefit after such research."

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Novo's Victoza beats Merck drug in diabetes study

Novo Nordisk's new diabetes drug Victoza proved more effective than Merck & Co's Januvia in a head-to-head study, boosting prospects for a product that has got off to a strong start in key markets.

Daily injections of both high- and low-dose Victoza reduced blood sugar levels by more than a daily tablet of Januvia in people with type 2 diabetes who had not responded adequately to the older drug metformin, researchers said on Friday.

The results may help the Danish drugmaker, which funded the study published in the Lancet journal, to differentiate its medicine in a highly competitive marketplace.

Victoza is Novo's biggest new drug hope and is expected to generate annual sales of more than $1.4 billion by 2014, according to consensus forecasts compiled by Thomson Reuters.

After a delayed path to market, prescription trends suggest it is now doing well in both Europe and the United States, in contrast to disappointing sales of some other recently launched new drugs, such as Eli Lilly's bloodthinner Effient.

Mads Krogsgaard Thomsen, Novo's chief scientific officer, said the results followed other positive comparative studies and would bolster Victoza's reputation among medical experts.

"The fact that Novo Nordisk has now done most, if not all, of the major comparator studies against different classes of oral and injectable anti-diabetic drugs really shows our commitment to showing comparative efficacy in a serious way," he said in a telephone interview.

Novo demonstrated two years ago that Victoza controlled blood sugar better than Byetta, a drug from the same class of medicine that is sold by Eli Lilly and Amylin Pharmaceuticals.

Progress Report

With investors awaiting a progress report on Victoza's sales prospects when Novo reports first-quarter results on April 27, Thomsen said demand for the new drug was following the company's own "optimistic" expectations.

"We have overtaken Byetta in several European markets in the first nine months post launch and in the U.S. we are already seeing, nine weeks into the launch, a rather sizeable uptake," he said.

In the latest study, 1.8 milligrams of Victoza, or liraglutide, lowered levels of HbA1c -- a standard blood measure that is indicative of a patient's glucose levels -- by 1.5 percentage points against 0.9 percent for Januvia, or sitagliptin.

The lower dose of 1.2 mg of Victoza cut HbA1C by 1.2 points in the six-month trial.

Researcher Dr Richard Pratley of the University of Vermont College of Medicine and colleagues said the difference was "clinically relevant," adding that patients on Victoza, which caused some nausea, also lost more weight.

In an accompanying comment, Dr Andre Scheen and Dr Regis Radermecker of Belgium's University of Liege said 1.2 mg of Victoza should be considered as a starting dose in most cases, with patients moving up to 1.8 mg if necessary.

On the downside, they noted that Januvia was cheaper, caused fewer gastrointestinal upsets and "one pill of sitagliptin daily might be judged as easier to administer than one subcutaneous injection of liraglutide daily."

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Merck's AIDS Triumph

Fifteen years ago, at the height of the AIDS epidemic, Merck researcher Daria Hazuda started work on a new drug to block the HIV virus from infiltrating people's DNA.

The odds seemed grim. Merck executives at one point advised her to switch to an alternative approach being explored by rival Pfizer . And as new combinations of antiviral pill seemed to put the HIV virus in check, Hazuda herself wondered whether there was really a need for another AIDS drug. But she kept working, even as several attempts at creating the drug foundered in early tests.

Hazuda's baby, Isentress, was approved in 2006 and was Merck's fastest growing medicine last quarter. Sales of the twice-a-day pill jumped 123% to $172 million in the second quarter at a time when the overall U.S. drug market may shrink for the first time in decades. On July 9, the drug was approved as a choice for patients who are just beginning treatment. Timothy Anderson at Sanford C. Bernstein estimates sales could someday hit $2 billion a year.

"I'm glad we stuck with it," says Hazuda, now Merck's vice president of antiviral drugs. "We hear people say it has really changed their lives."

The Isentress story turns the drug industry's now-customary narrative--that small companies out-invent big ones--on its head. It's also a reminder for Merck as it braces for the inevitable culture shocks likely to result from its $41 billion merger with Schering-Plough . The prospects of a new drug are precarious, with only one in nine drugs tested in humans making it to the market. Hundreds of millions of dollars, the work of hundreds of scientists and 10 years or more will go into the effort. Yet it's often the grit and stamina of a single researcher that gets a medicine to patients.

Hazuda joined Merck in 1989 after finishing her doctorate at the State University of New York, Stony Brook. She was 30. Initially she was assigned to work on flu, but asked to be switched to HIV work. "If there was one virus worth working on, it was HIV," she says.

In 1993, virus researcher and Nobel laureate Harold Varmus, who was just about to take over as head of the National Institutes of Health, called for researchers to search for drugs to target integrase--the enzyme that Isentress would attack.

HIV copies itself by splicing into the DNA of the people it infects and being copied when their cells replicate. Integrase is the enzyme that makes the cut. Block integrase, the logic went, and the virus could not spread from cell to cell. Aside from Merck, the companies now known as GlaxoSmithKline , Sanofi-Aventis and Bristol-Myers Squibb were all searching for integrase blockers.

The first challenge was figuring out how to measure whether or not chemicals were blocking the integrase enzyme so that hundreds of different potential medicines could be tried out. She and her small team of researchers succeeded in 1993, but couldn't get any notice for their work. The Conference on Retroviruses and Opportunistic Infections, one of the biggest AIDS conferences rejected it, as did several big publications. The paper was finally published in 1994 in Nucleic Acids Research, a less prominent journal.

Then, in 1996, everything about HIV drug research changed. Results of studies combining three or four antiviral drugs at once were presented. These drug cocktails could keep HIV from ever developing into full-blown AIDS, in which the immune system fails. Scientists had commuted a death sentence.

Was there even a need for new HIV medicines? Hazuda herself was having doubts until she saw a Paul Volberding, a pioneering San Francisco doctor who had started the first program in the U.S. dedicated to treating AIDS, tell the story of a patient who had died despite the new drug cocktails. New drugs were still needed.

Just as she was getting back to work, researchers found a mutation in prostitutes and gay men that protected them from HIV infection. Other companies, including Pfizer and Schering-Plough, started developing drugs to target the gene, called CCR5. "Very senior management said I should stop working on integrase and start working on CCR5 inhibitors," Hazuda says. But she insisted the right target was integrase, part of the virus, not CCR5, which is part of the patient.

Hazuda went back to her West Point, Pa., lab. But she couldn't get her drug screen for integrase blockers to work with the robots Merck had at the time. In the summer of 1999, she and two associates squirted 250,000 different compounds by hand into plates containing the integrase enzyme. A chemical from xylaria, a fungus that grows on dead wood, blocked it. The molecule was too complicated to make into a drug, but, Hazuda says, "It provided a glimmer of hope."

Finally, a few chemicals looked like they might work. In 2000 Hazuda and her team published two landmark papers showing that integrase inhibitors could be made. The first four chemicals they tried fizzled out in early studies. The fifth was a chemical synthesized by Merck researchers in Rome who were searching for hepatitis C drugs. That became Isentress.

Isentress was approved in 2007 for patients whose viral counts were rising despite AIDS drug therapy. Sales of Pfizer's CCR5 drug are so small that the company doesn't break them out, but a once-a-day drug from Gilead is advancing through clinical trials now.

What's next? Recently Merck researchers found potential HIV drug targets by scanning the human genome. And Hazuda thinks there may be other ways to attack the virus too. "We haven't run out of ideas," she says. Merck better hope not.

Source : news.alibaba.com

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Sleep And Obesity Connection Explored By New Drug From Merck

A group of scientists working in the research laboratories at the pharmaceutical company Merck have recently been conducting studies which confirmed the link yet again. In fact their study made use of a new drug which was designed to have an effect on the natural body functions which are linked to both sleep and body weight. When the scientists gave the lab mice the drug along with a high fat diet they put on less weight than those mice who were not given the drug and who followed the same diet.

The drug was developed to have an affect on T-type calcium channels which previous research has shown to be part of the sleep and weight gain function of the human body. By targeting these T-type calcium channels they were able to prevent weight gain in the lab mice. The scientists spoke about how the drug was aligning feeding patterns with the natural circadian rhythms of the mice.

This drug is still at a very experimental stage but Merck are confident that something could come out of its research which may help people who have weight problems to shed the pounds. Many more years of research will be needed before anything concrete can be presented to the Food and Drug Administration and the European health authorities for regulatory approval. The weight loss drug market is one of the most lucrative in the pharmaceutical industry.

The pharmaceutical company Merck is probably best known for its male pattern baldness remedy Propecia which they first developed as a treatment for prostate problems in men.

Source : www.ukmedix.com

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Merck Suffers Blow Developing New Migraine Drug

Merck, maker of the Maxalt migraine drug, has been betting heavily on adding a new medicine to its lineup aimed at the multibillion-dollar migraine market. The company has been planning to ask the FDA this year to approve the medicine, telcagepant, and analysts predicted the drug could have $800 million or more in sales in 2015. Analysts considered telcagepant one of Merck’s key new products.

But the drug maker announced this morning that it would delay taking telcagepant to the FDA, and one analyst wondered whether the drug would ever make it. “It is fully conceivable that this product will be terminated,” Sanford Bernstein’s Tim Anderson wrote in a note to investors.

The problem: some patients participating in an exploratory study gauging whether the drug could be taken daily to prevent migraines developed high levels of liver enzymes. The company stopped the study and is reviewing data from another study, said Peter Kim, Merck’s research chief. Meantime, it is moving ahead with studies of the drug’s intermittent use to treat migraine attacks.

Merck disclosed the telcagepant news in announcing disappointing financial results for the first quarter.

The struggles are another reminder of the unpredictability of drug research and development, and the difficulties that Merck and other big pharmaceutical companies have had finding lucrative new drugs to replace the blockbusters losing patent protection over the next several years.

More than a third of Merck’s revenues come from drugs whose patents run out through 2013, according to Edward Jones’ Linda Bannister. The depth of its “patent cliff” is so steep that Merck, which had prided itself on its homegrown research, is now inking drug development deals with outside firms. More telling, it agreed to buy Schering-Plough for $41.1 billion.

Seamus Fernandez, a Leerink Swann analyst, told the Healh Blog that the telcagepant news — combined with its poor first-quarter performance — “increases the importance of a successful merger outcome.” In a conference call with analysts, Merck officials said the merger, slated for completion in the fourth quarter, was on track.

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