Indacaterol : A Novel Beta2-agonist for Asthma and COPD
May 24, 2005, 10:54, Reviewed by: Dr.
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"These data show indacaterol has significant therapeutic potential, including single-dose 24-hour control, for asthma and COPD patients."
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By Novartis Pharmaceuticals ,
Novartis' development compound indacaterol (QAB149) may provide a new standard for beta2-agonist therapy in
patients with asthma and chronic obstructive pulmonary disease (COPD), according to data presented at the centenary meeting of the American Thoracic Society (ATS) this week. The collective data from Phase II studies show
indacaterol provides bronchodilation for up to 24-hours, with convenient once-daily dosing.
"Respiratory disease is an important therapeutic area of focus at Novartis," said Alex Gorsky, Chief Operating Officer, Novartis Pharmaceuticals Corporation. "We have designed an ambitious development program for indacaterol and other compounds, such as the recently licensed anticholinergic AD237. We look forward to making new single and combination treatments available for the millions of patients who need them."
Results in Patients
A randomized, double-blind, dose-ranging study (50, 100, 200, 400 ug or placebo) in 42 patients with intermittent or mild to moderate persistent asthma demonstrated effective 24-hour bronchodilation within five minutes and a favorable safety profile with once-daily dosing. Improvements in efficacy were generally dose dependent, while safety and tolerability were similar to placebo.(i)
"Despite advances in the management of these chronic conditions, the numbers of individuals affected by asthma and COPD are large and growing," said James Donohue, M.D., Professor of Medicine, Chief, Division of Pulmonary Critical Care, University of North Carolina School of Medicine. "These data show indacaterol has significant therapeutic potential, including single-dose 24-hour control, for asthma and COPD patients."
A further randomized, double-blind, placebo-controlled, parallel-group, multicenter study involving 156 patients aged 13-75 demonstrated that indacaterol was shown to have a favorable cardiovascular safety profile, with no clinically significant effect on ECG measurements, vital signs or laboratory tests commonly affected by long-duration beta2-agonists.
No clinically notable changes occurred in the mean QTc intervals for any treatment group at any time point (calculated using Fridericia's formula). No clinically or statistically significant changes in serum potassium and blood glucose, or evidence of dose-related increases in adverse events were detected. In addition, no serious adverse events occurred in any active treatment group.(ii)
Indacaterol pre-clinical studies
In addition, extensive pre-clinical studies involving indacaterol also were presented. In isolated human bronchi, indacaterol provides effective bronchodilation with a longer duration of action than albuterol and formoterol
and an onset of action more rapid than salmeterol and comparable to albuterol.
At resting tone, the onset of action of indacaterol (9.2 plus or minus 1.5min, n=8) was not significantly different from that of formoterol (5.8 plus or minus 0.8min, n=8) and albuterol (11.0 plus or minus 3.6min, n=8) but was significantly faster than that of salmeterol (18.0 plus or minus 3.5min, n=8; p less than 0.05).(iii)
In addition, indacaterol was shown to be a potent beta2-agonist that, in contrast to salmeterol, does not antagonize the bronchorelaxant effect of a short-acting beta2-agonist.
Other pre-clinical data demonstrate that indacaterol provides a long duration of action and fast onset in vitro and in vivo in the guinea-pig. The risk of tachyphylaxis, or rapidly decreasing response to a drug, was assessed
in once-daily intratracheal (IT) dosing of indacaterol compared with formoterol and salmeterol. Conscious guinea-pigs were then challenged with aerosolized 5-HT (175ug/mL, 1 min) 2 hours after beta2-agonist exposure following both single and 5 daily IT treatments and bronchoconstriction
quantified by plethysmography. No tachyphylaxis was observed with indacaterol, formoterol or salmeterol.(iv)
Significant Disease Burden
COPD incurs a significant burden on the U.S. healthcare system in terms of number of visits and medications prescribed. Among the papers presented at the ATS meeting was an analysis of data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey conducted by a team of researchers from Novartis Pharmaceuticals, Rutgers University and Duke University that assessed the disease burden. Results showed that during 2002, 9.9 million ambulatory visits were made to physician offices, outpatient departments and emergency departments in the U.S., representing a 50.1% increase from 2001. In addition, the annual rate of visits for COPD across
all settings was 34.4 visits per 1,000 persons in the U.S. population.(v)
"Asthma-related suffering, cost and death can be greatly reduced through treatment with effective medications," said Mike Tringale, M.S.M., Director of Marketing and Communications at the Asthma and Allergy Foundation of America. "We look forward to seeing what benefit this new treatment will provide and to having a new treatment option for patients."
About Asthma and COPD
Exploring new treatments for asthma and COPD is critical. Despite a wide range of currently available therapeutic options, respiratory diseases affect millions of patients around the world. For example, asthma, which affects
more than 23 million people in the U.S., is the sixth most common chronic condition overall. In addition, the estimated number of asthma-related deaths is approximately 5,000 per year.(vi) COPD is presently the fourth leading
cause of death worldwide and is expected to be the third leading cause of death by 2020. While COPD death rates are very low under the age of 45, complications and deaths increase steeply with age.(vii) 
- The data were presented at the centenary meeting of the American Thoracic Society (ATS) this week.
www.novartis.com
The foregoing release contains certain forward-looking statements that can be identified by terminology such as "may provide," "significant therapeutic potential," "promising" or similar expressions, or by discussions regarding the potential of indacaterol will be approved for marketing, or regarding any potential revenues from indacaterol. Such forward-looking statements involve
known and unknown risks, uncertainties and other factors that may cause actual results with indacaterol to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that indacaterol will be approved for sale in any market. In particular, management's expectations regarding commercialization of indacaterol could be affected by, among other things, uncertainties relating to clinical trials; new clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; as well as other risks and factors referred to in the Company's current Form 20-F on file with the US Securities and Exchange Commission.
Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is
providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
About Novartis
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS) - a world leader in pharmaceuticals and consumer health. In 2004, the Novartis Group's businesses achieved sales of USD 28.2 billion and pro forma net income of USD 5.6 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 81,400 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
References
(i) Beeh K-M, Schelfout V, Gronke L, Kaniess F, Cameron R, van As A. Indacaterol (QAB149): the first once-daily beta2-agonist with 24 -hour bronchodilation. Abstract 1314, poster board number G34.
(ii) Chuchalin AG, Tsoi AN, Richter K, Arievich H, Cameron R, Bao W, vanAs A. Cardiovascular safety of indacaterol (QAB149), a novel 24-hour beta2-agonist, in patients with asthma. Abstract 1316, poster board number G35.
(iii) Naline E, Molimard M, Fairhurst R, Trifilieff A, Advenier C. Duration and onset of action of indacaterol (QAB149), a novel 24-hour beta2-agonist, on the isolated human bronchus. Abstract 1296, poster board number G32.
(iv) Battram CH, Mok J, Lewis CA. Once-daily administration of indacaterol (QAB149) does not induce tachyphylaxis in vivo. Abstract 2569, poster board number G37.
(v) Lau H, Valiyeva E, Suh D, Mahajan S. Characteristics of ambulatory care visits for chronic obstructive pulmonary disease in 2002 in a national sample of the U.S. population. Abstract 3636, poster board number J115.
(vi)http://www.ncqa.org/somc2001/asthma/somc_2001_asthma.html
(vii) http://www.thoracic.org/COPD/2/epidemiology.asp
Contact
Maura Bergen
Novartis Pharmaceuticals Corporation
Tel 862 778 4146
or mobile 917 334 0903
[email protected]
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