NEW YORK, Aug 27, 2009 (BUSINESS WIRE) -- Forest Laboratories, Inc. (NYSE: FRX), an international pharmaceutical
manufacturer and marketer and Nycomed, a privately owned pharmaceutical
company, today announced that results of four phase III trials have been
published in the prestigious peer-reviewed medical journal The Lancet
showing that roflumilast, a phosphodiesterase 4 (PDE4) inhibitor,
improved lung function and reduced exacerbations in patients with
moderate to severe COPD.
COPD is an under-diagnosed progressive lung disease that may lead to
death. Worldwide, COPD kills four people every minute and the World
Health Organization (WHO) predicts that it will be the third leading
cause of death by 2030. WHO estimates that 80 million people have
moderate to severe COPD.
Roflumilast, a once-a-day oral tablet, would be the first in an entirely
new class of treatment for COPD if it receives regulatory approval from
the authorities in Europe (EMEA) and the US (FDA). The phase III
placebo-controlled trials of roflumilast evaluated the treatment in two
12-month (Lancet 2009; 374: 685-694) and two six-month studies (Lancet
2009; 374: 695-703), involving 4,500 patients in ten countries. Details
of the results of the four studies will be published in The Lancet
on August 29 (data and information under embargo until Friday, August 28
at 00:01am GMT).
The two 12-month studies published in The Lancet demonstrated
that roflumilast produced a statistically significant and clinically
relevant reduction in exacerbations (lung attacks that need treatment
with systemic steroids or lead to hospitalisation), even for patients
who were also taking long-acting bronchodilators. The studies showed a
reduction in moderate to severe exacerbations by 17 percent per patient
per year (rate of 1.14 events per year with roflumilast vs. 1.37 per
year with placebo, p<0.001). The reduction in exacerbations was
irrespective of concomitant treatment with long-acting beta-2 agonists,
a standard bronchodilator therapy.
When added to standard bronchodilator therapies in the two six-month
studies, a clear trend for the reduction of exacerbations was observed
with roflumilast, over and above what was achieved with these therapies
alone. There was also a statistically significant difference with
roflumilast in other prespecified endpoints, including median time to
first exacerbation (moderate to severe in the salmeterol study, and
mild, moderate and severe in the tiotropium study) and in the proportion
of patients in both studies experiencing a mild, moderate, or severe
exacerbation.
Lung function, as measured by FEV1 (how much volume can be
exhaled in one second), was the primary or co-primary endpoint in all
four studies. Across the studies, roflumilast demonstrated a
statistically significant improvement in pre-bronchodilator FEV1,
in the range of 48 to 80 mL (p<0.001).
Nausea, diarrhea and weight loss were the most common adverse events
recorded in patients in the four trials, but they were generally mild to
moderate in intensity and generally occurred in the first weeks of
treatment.
Professor Peter Calverley, Professor of Respiratory Medicine, University
of Liverpool, UK, and the lead author of the 12-month studies, said:
"COPD can devastate people's lives and exacerbations can be extremely
frightening, so a novel tablet like roflumilast is really exciting for
those of us treating patients. Roflumilast acts differently to
bronchodilators as it acts on the underlying condition, not primarily
impacting on everyday symptoms. It acts slowly and the effects, as we
saw in our studies, are gradual and sustained."
"Roflumilast could be an important new treatment for COPD," added
Professor Fernando Martinez, University of Michigan, also a lead author
of the 12-month studies. "We clearly need new options for patients with
COPD and the results of these studies, published in The Lancet,
confirm that roflumilast is beneficial. It reduced exacerbations, or
lung attacks, and significantly improved lung function, in a patient
population whose lung function is very poor."
Professor Leonardo Fabbri, Professor of Respiratory Medicine, University
of Modena and Reggio Emilia, Italy, and lead author of the six-month
studies, said: "Roflumilast has a novel mode of action and has the
potential to become the first of a new class of drugs and potentially
the only completely new treatment option for COPD in the next several
years. These eagerly awaited results, published this week in The
Lancet, show that in addition to confirming the sustained
statistically significant improvements in lung function, roflumilast
also showed a trend to reducing exacerbations when given in addition to
long acting inhaled bronchodilators. The results of the two six-months
trials examining the additive effect of roflumilast on top of salmeterol
or tiotropium support and extend the findings of the 12-month trials, by
showing a clinically relevant lung function improvement in patients with
impaired lung function on top of maximum bronchodilation."
"The lung function improvements on top of current bronchodilation
clearly indicates that roflumilast improves lung function over and above
what can be achieved with other COPD treatments alone. It also
demonstrates that roflumilast works in a different way to current
treatments and supports roflumilast's potential to change how COPD is
managed," added Professor Klaus Rabe, Professor of Medicine at Leiden
University Medical Center, also a lead author of the six-month studies.
Nycomed's Executive Vice President R&D, Anders Ullman, said: "We are
very pleased with the results published in The Lancet this week.
In four studies, two 12-month studies and two six-month studies,
roflumilast showed clear therapeutic potential, decreasing exacerbations
and improving lung function. The uniformity of the results is really
encouraging and gives us great hope that our faith in roflumilast has
been confirmed. We are now undergoing the regulatory review process with
the European and US authorities."
"Based on the results from the pivotal studies published this week, it
appears that roflumilast provides added activity on top of other
commonly used treatments for COPD," said Lawrence S. Olanoff, President
and Chief Operating Officer of Forest Laboratories. "Roflumilast
represents the first in a new class of agents to treat COPD and, if
approved, would be the first oral anti-inflammatory maintenance
treatment for the disease."
About Roflumilast (Daxas(R))
Roflumilast is an orally administered phosphodiesterase 4
(PDE4) enzyme inhibitor targeting cells and mediators in the body
believed to be important in the COPD disease process. Roflumilast is
expected to act on the underlying mechanism of COPD and related
inflammatory diseases. If approved, roflumilast, a once-a-day oral
tablet, will be the first in an entirely new class of treatment for
COPD. It will also be the first oral anti-inflammatory treatment for
COPD patients. Current treatment for COPD patients includes the use of
inhaled bronchodilators and inhaled corticosteroids.
About COPD
COPD is an under-diagnosed progressive lung disease that may lead to
death. Worldwide, COPD kills four people every minute and the World
Health Organization (WHO) predicts that it will be the third leading
cause of death by 2030. WHO estimates that 80 million people have
moderate to severe COPD.
Symptoms of COPD include breathlessness, chronic cough and excessive
production of phlegm. A significant worsening of symptoms called an
exacerbation or lung attack can last several weeks. Breathing becomes
severely compromised and patients may need to be admitted to hospital.
Exacerbations are frightening events resulting in increased patient
anxiety, worsening health status, lung function decline and increased
risk of death.
Smoking is a major contributory factor in western countries, and
pollution from fires for cooking and heating is an additional
contributory factor in less developed countries. Industrial and chemical
pollutants can also cause COPD.
Chronic inflammation in the lungs plays a significant role in COPD.
Current medications used to treat the condition deal mainly with
symptoms rather than the underlying disease. Roflumilast is a new PDE4
inhibitor being developed specifically to target the chronic
inflammation which is COPD-related.
About Nycomed
Nycomed is a privately owned global pharmaceutical company with a
differentiated portfolio focused on branded medicines in
gastroenterology, respiratory and inflammatory diseases, pain,
osteoporosis and tissue management. An extensive range of OTC products
completes the portfolio.
Its R&D is structured around partnerships and in-licensing is a
cornerstone of the company's growth strategy.
Nycomed employs 12,000 associates worldwide, and its products are
available in more than 100 countries. It has strong platforms in Europe
and in fast-growing markets such as Russia/CIS and Latin America. While
the US and Japan are commercialised through best-in-class partners,
Nycomed plans to further strengthen its own position in key Asian
markets.
Headquartered in Zurich, Switzerland, the company generated total sales
of EUR 3.4 billion in 2008 and an adjusted EBITDA of EUR 1.2 billion.
For more information visit www.nycomed.com
About Forest Laboratories
Forest Laboratories (NYSE: FRX) is a U.S.-based pharmaceutical company
with a long track record of building partnerships and developing and
marketing products that make a positive difference in people's lives. In
addition to its well-established franchises in therapeutic areas of the
central nervous and cardiovascular systems, Forest's current pipeline
includes product candidates in all stages of development and across a
wide range of therapeutic areas. The company is headquartered in New
York, NY. To learn more about Forest Laboratories, visit www.FRX.com.
Except for the historical information contained herein, this release
contains forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. These statements involve a
number of risks and uncertainties, including the difficulty of
predicting FDA approvals, the acceptance and demand for new
pharmaceutical products, the impact of competitive products and pricing,
the timely development and launch of new products, and the risk factors
listed from time to time in Forest Laboratories' Annual Report on Form
10-K, Quarterly Report on Form 10-Q, and any subsequent SEC filings.
Notes to editors
Further details for the four trials will be presented at the European
Respiratory Society Annual Congress 2009, in Vienna, Austria, September
12 to 16, 2009.
12-Month Trials
The two replicate, 12-month trials were randomised, placebo controlled
and double blind. One 12 month study was conducted in 246 centres in 10
countries and the second was conducted in 221 centres in eight countries.
COPD patients were over 40, and either former or current smokers with a
smoking history of at least 20 pack-years. The patients had symptoms of
chronic cough and sputum, their post-bronchodilator FEV1 was
less-than or equal to 50% of the predicted value and they had at least one documented
moderate to severe exacerbation in the previous year. Approximately 50%
of the patients were concomitantly using long acting beta agonists.
Patients were permitted to use short-acting bronchodilators to relieve
their symptoms as needed.
Compared with placebo, roflumilast significantly reduced the rate of
exacerbations and improved lung function in treated patients. The rate
of moderate to severe exacerbations in the study period (pooled data)
was 1.14 per year in the patients treated with roflumilast compared with
1.37 per year, in the placebo group. This represents an improvement of
17 per cent (RR 0.83; CI 0.75-0.92, p<0.001).
The pooled data for lung function using the pre-bronchodilator FEV1 measurement
(forced expiratory volume in one second) showed an average increase of
48mL (p<0.001) in roflumilast treated patients compared with the placebo
group. The improvement in post-bronchodilator FEV1 was 55mL
(p<0.001) with roflumilast.
The differences found in exacerbation rates and lung function were
similar irrespective of whether roflumilast was used with or without a
long-acting beta-agonist.
Using another measurement, FVC (forced vital capacity, the lung capacity
measured when the patient is exhaling for as hard and as long as
possible) roflumilast patients also scored higher with an average
increased FVC of 98 mL (p<0.001) compared with the placebo group. These
patients had not used a bronchodilator prior to testing. The improvement
in post-bronchodilator FVC was 101 mL (p<0.001).
Roflumilast was well tolerated by most patients. Slightly more patients
discontinued the trial in the roflumilast group than those taking
placebo (14 percent vs 11 percent). Diarrhea, nausea and headache were
the commonest reasons for discontinuation. A reduction in weight, around
2kg, was seen consistently across all the studies published in The
Lancet. When patients stopped taking roflumilast the majority regained
weight. In addition, in the 12- month studies, only four patients out of
1,547 dropped out because of weight loss.
Six-month trials
In the six-month trial patients used roflumilast or a placebo in
conjunction with commonly used long acting bronchodilators (inhalers).
In one trial, patients used salmeterol with roflumilast or placebo. In
the second trial, patients used tiotropium, a long-acting bronchodilator
which also reduces the production of mucus, with roflumilast or placebo.
Patients used "rescue mediation" short-acting bronchodilators, as needed.
There were 933 patients in the salmeterol trial and 743 patients in the
tiotropium trial. Overall patients had moderate to severe COPD; were
over 40, current or former smokers with a history of smoking at least a
pack a day for 10 years. In contrast to the 12-month trials, patients in
the six-months trials did not require a history of exacerbations.
Patients recruited to the tiotropium study were more symptomatic than
those in the salmeterol study as they were required to have daily
chronic cough and sputum production and a documented use of rescue
medication.
Patients were seen and measured once a month for the first three months
and every six weeks for the last three months of the trial.
Compared with placebo, patients taking roflumilast in addition to
salmeterol, had an average increased pre-bronchodilator FEV1
(forced expiratory volume in one second) of 49mL (p<0.001).
Compared with placebo, patients taking roflumilast in addition to
tiotropium had an average increased pre-bronchodilator FEV1 of
80mL (p<0.001).
There was a similar FEV1 advantage in both trials when
measurements were taken after using a short-acting bronchodilator, an
increase of 60mL (p<0.001) in the salmeterol study and 81mL (p<0.001) in
the tiotropium study.
Roflumilast was well tolerated by most patients. Slightly more patients
discontinued the trials in the roflumilast group than those taking
placebo (13 percent vs 8 percent). Diarrhea, nausea and headache were
the most commonly reported adverse events.
SOURCE: Forest Laboratories, Inc. and Nycomed
Nycomed
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