Boehringer Ingelheim enrols first patient in Phase III program for new once-daily fixed-dose combination of tiotropium plus olodaterol in COPD
Ingelheim, Germany, September 21, 2011
– Boehringer Ingelheim today announced enrolment has
commenced in its TOviTO Phase III clinical trial program. It will
investigate tiotropium plus olodaterol in a once-daily fixed-dose
combination for the treatment of chronic obstructive pulmonary
disease (COPD).
A progressive yet treatable disease that restricts patients’
lives over time, COPD is estimated to affect over 210 million
people worldwide and results in more deaths than breast cancer and
diabetes combined. 1,2
Tiotropium - marketed under the brand name Spiriva® in COPD
– is a long-acting muscarinic antagonist (LAMA) that provides
24-hour bronchodilation by blocking M 3 muscarinic
receptors. 3 Tiotropium is the most prescribed COPD drug
worldwide with more than 34 million patient years. Olodaterol is a
novel once-daily long-acting Ăź 2-agonist (LABA)
that Boehringer Ingelheim has developed as an ideal partner to
tiotropium in COPD.
Boehringer Ingelheim has decided to move the once-daily fixed-dose
combination of tiotropium plus olodaterol into the TOviTO Phase III
trial program on the back of promising olodaterol Phase III trial
results, which will be published in the near future. The TOviTO
program includes several trials that will provide important
evidence to support olodaterol’s potential to improve
patients’ lives beyond optimal bronchodilation. The first two
trials to begin in the comprehensive TOviTO program will be TOnado
1 and its replicate study, TOnado 2. TOnado 1 & 2 will be the
first two pivotal studies to evaluate the safety and efficacy of
the fixed-dose combination for the treatment of COPD patients, and
are planned to involve 5000 patients (2500 each) at more than 500
trial sites in approximately 40 countries.
The trials are multi-centered, multi-national, randomised,
double-blind, parallel group studies that will compare the efficacy
and safety of tiotropium plus olodaterol in fixed-dose combination
with that of both mono-compounds (tiotropium and olodaterol). Both
the fixed-dose combination and monotherapies will be administered
once-daily, for 52 weeks, via Boehringer Ingelheim’s
Respimat® Soft Mist™ Inhaler (SMI). Respimat® SMI is
a new generation inhaler that provides a unique slow moving and
long-lasting soft mist 4,5 that is easy to inhale
6 and produces superior lung deposition. 7,8
Respimat® SMI is preferred by patients compared to other
currently available inhalers. 9,10,11
Professor Roland Buhl, Head of the Pulmonary
Department at the University of Mainz, Germany, and the
Co-ordinating investigator for both trials, said: “We
hypothesise the combination of tiotropium plus olodaterol, in a
single Respimat® Inhaler device, will provide superior efficacy
compared with the once-daily mono compounds. The addition of a LABA
to tiotropium, a current COPD standard-of-care, could represent a
significant advancement in COPD treatment. For the first time,
patients would be able to receive their once-daily dose of
tiotropium alongside a specifically selected LABA, all in the one,
convenient inhaler.”
The trials’ primary endpoints will be bronchodilation –
as measured by FEV 1a AUC
0-3hb response and trough FEV 1
response at 24 weeks - and health status (quality of life) –
as measured by the Saint George’s Respiratory Questionnaire
(SGRQ).
Professor Klaus Dugi, Corporate Senior Vice
President Medicine, Boehringer Ingelheim, said: “Boehringer
Ingelheim is committed to advancing respiratory research and
treatment. The development of a true once-daily LABA as a partner
to tiotropium underscores the company’s commitment to meet
the unmet medical needs of COPD patients and improve clinical
outcomes. Our goal is to provide patients with a LABA/LAMA
fixed-dose combination in a device that was specifically designed
with patient benefit and convenience in mind.”
aForced Expiratory Volume in one second
bArea Under the Curve from 0 to 3 hours post-dose
About COPD
Chronic Obstructive Pulmonary Disease (COPD) is a major
cause of death and disability throughout the world. Symptoms
include cough, sputum (mucus or phlegm) production, and
breathlessness on exertion. Acute worsening of these symptoms, i.e.
exacerbations (sometimes referred to as COPD lung attacks due to
their severe impact on patients’ health) often occurs and can
restrict a patient’s ability to perform normal daily
activities. 12 The latest World Health Organisation
(WHO) figures estimate that more than 3 million people died from
the disease in 2005. Dyspnoea (breathlessness), the main symptom of
COPD, is characteristically persistent and progressive and has a
serious impact on patients’ quality of life. 12 At
its most severe form, it even limits a patient performing simple
tasks such as washing and dressing.
About Olodaterol
Olodaterol is a long acting β
2–agonist (LABA) in clinical development (Phase
III) by Boehringer Ingelheim. It is being developed as an ideal
partner to tiotropium. Phase III studies have confirmed olodaterol
has a 24-hour duration of action and bronchodilator efficacy in
patients with COPD when administered once-daily. Olodaterol as
monotherapy showed promising results in Phase III that met the
company’s expectations and will be published in the near
future.
About Tiotropium
Tiotropium (Spiriva®) is a long-acting inhaled
anticholinergic medication and is the first inhaled treatment to
provide significant and sustained improvements in lung function
with once-daily dosing. Tiotropium positively impacts the clinical
course of COPD, helping to change the way patients live with their
disease 13,14 by opening narrowed airways and helping to
keep them open for 24 hours. Tiotropium works through targeting a
dominant reversible mechanism of COPD – cholinergic
bronchoconstriction (closing of the airways) – and has
demonstrated significant and sustained bronchodilation
15 (opening of the airways) and reduction in
hyperinflation 16,17 (air trapping). Boehringer
Ingelheim has marketed tiotropium as Spiriva® since 2002 (9
years).
About Respimat® Soft Mist™ Inhaler
Developed by Boehringer Ingelheim, Respimat® Soft
Mist™ Inhaler (SMI) is a propellant-free, new generation
inhaler with a unique delivery mechanism. It produces a
long-lasting, slow moving Soft Mist™ 4,5 that is
easy to inhale, easy to co-ordinate (forced inhalation is not
required), reduces deposition in the mouth and throat and leads to
superior lung deposition. 6,7,8 Therefore, Respimat®
SMI is preferred by patients compared to other currently available
inhalers. 9,10,11
Boehringer Ingelheim: Leading respiratory forward
Treatment of COPD has been a major area of focus for
Boehringer Ingelheim for decades and significant resources are
dedicated to research in this field. More recently, the Company has
also branched out into developing treatment options for other
airway diseases, including asthma, lung cancer, idiopathic
pulmonary fibrosis and other respiratory indications. Boehringer
Ingelheim’s respiratory portfolio covers a wide range of
treatment options and includes Spiriva® (tiotropium),
Berodual® (fenoterol/ipratropium bromide), Berotec®
(fenoterol), Combivent® (ipratropium bromide/salbutamol) and
Atrovent® (ipratropium bromide).
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the
world’s 20 leading pharmaceutical companies. Headquartered in
Ingelheim, Germany, it operates globally with 145 Operating Units
(OPUs) and more than 42,000 employees. Since it was founded in
1885, the family-owned company has been committed to researching,
developing, manufacturing and marketing novel products of high
therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim is
committed to socially responsible programs. Involvement in social
projects, caring for employees and their families, and providing
equal opportunities for all employees form the foundation of the
global operations. Mutual cooperation and respect, as well as
environmental protection and sustainability are intrinsic factors
in all of Boehringer Ingelheim’s endeavours.
In 2010, Boehringer Ingelheim posted net sales of about 12.6
billion euro while spending almost 24% of net sales in its largest
business segment Prescription Medicines on research and
development.