COPD investigational treatments: an interview with Dr. Tunde Otulana, Senior Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.

Interview conducted by April Cashin-Garbutt, MA (Editor)Oct 21 2013

Please can you give a brief introduction to Olodaterol?

Olodaterol is a long-acting beta2-agonist (LABA) bronchodilator delivered via the Respimat^® inhaler. It is being investigated as a once daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Investigational studies have shown statistically significant improvement in lung function as measured by FEV₁ over 24 hours.

How important have long-acting beta agonists (LABAs) been in the treatment of chronic obstructive pulmonary disease (COPD) and how does Olodaterol differ from previous LABAs?

Bronchodilator medications are central to the symptomatic management of COPD. They are given on an as-needed basis or on a regular basis to prevent or reduce symptoms.

There are no head-to-head comparative studies between olodaterol and other COPD therapies, from which superiority or inferiority conclusions can be drawn.

Please can you outline the Phase 3 clinical program on Olodaterol? What did the data from these studies reveal?

The Phase 3 program evaluated olodaterol delivered via the Respimat^® inhaler compared to placebo in more than 3,500 patients with moderate, severe and very severe COPD (stages II, III and IV as defined by the Global Initiative for Chronic Obstructive Lung Disease [GOLD]).

The trials were conducted in a patient population representative of those seen in clinical practice. In an effort to more accurately represent the clinical practice setting, patients involved in the studies were allowed to continue their usual care, with the exception of long-acting beta agonists. Usual care included long- and short-acting anticholinergics, short-acting beta agonists, inhaled corticosteroids and xanthines.

In one set of 48-week Phase 3 pivotal studies (NCT00782210 and NCT00782509), olodaterol 5 and 10 µg delivered once daily via the Respimat® inhaler provided statistically significant improvements in lung function, as measured by FEV₁, versus placebo plus usual care in patients with moderate to very severe COPD (P < 0.05; n=613 and 635).

In a second set of 48-week studies (NCT00793624 and NCT00796653), the same dose and delivery of olodaterol provided comparable improvements in lung function compared to 12 µg formoterol twice daily in these COPD patients (n=904 and 934). After 24 weeks of treatment, both doses of olodaterol and formoterol provided statistically significant improvements in FEV₁ AUC_0-3.

Olodaterol 5 µg was shown to provide significant improvement (P < 0.0001) in lung function within five minutes following the first dose. In addition, COPD patients had less need for both day- and night-time rescue medication when using both doses of olodaterol (5 and 10 µg) delivered once daily via the Respimat® inhaler and formoterol versus placebo over the 48-week treatment period (P < 0.01).

Further, in the two replicate, randomized, double-blind, placebo-controlled crossover six-week studies, patients received olodaterol 5 µg and 10 µg delivered once daily via the Respimat^® inhaler, tiotropium 18 µg once daily via the HandiHaler^® or placebo in addition to usual care (ICS and xanthines) for 6 weeks (n=108 and 122).

The data presented at the European Respiratory Society (ERS) Annual Congress 2013 showed that the improvements seen in lung function with olodaterol, as measured by FEV₁ responses, were maintained over 24 hours (P < 0.001). For more information, please see the Boehringer Ingelheim press release announcing the olodaterol data at ERS.

As a result of the improved lung function, did patients have less need for rescue medications?

Data from the olodaterol Phase 3 clinical program showed the addition of olodaterol 5 and 10 µg delivered once daily via the Respimat® inhaler provided improvements in lung function in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

In addition, COPD patients had less need for both day- and night-time rescue medication when using both doses of olodaterol (5 and 10 µg) delivered once daily via the Respimat® inhaler and formoterol versus placebo over the 48-week treatment period (P < 0.01).

Did patients experience any adverse reactions to Olodaterol?

In the two sets of replicate, 48-week pivotal studies, there was no significant difference in adverse events between the olodaterol treatment arm and the control arm with 71.0 percent of patients receiving olodaterol 5 µg reporting an adverse event compared to 72.7 percent of patients receiving olodaterol 10 µg, 70.8 percent of patients receiving placebo and 69.1 percent of patients receiving formoterol 12 µg. The most common adverse reactions were nasopharyngitis, dizziness, rash and arthralgia.

In the two replicate, randomized, double-blind, placebo-controlled crossover six-week studies, there was no significant difference in adverse events between the olodaterol treatment arm and the placebo arm.

Reported Adverse Events - Study 1:

• Olodaterol 5 µg: 31.7 percent
• Olodaterol 10 µg: 33.7 percent
• Placebo: 34.3 percent

Reported Adverse Events - Study 2:

• Olodaterol 5 µg: 35.7 percent
• Olodaterol 10 µg: 38.9 percent
• Placebo: 33.9 percent

The most common adverse reactions were nasopharyngitis, COPD, cough and dyspnea.

How do these results add to the advances in the treatment of COPD?

Despite the advances made in recent years in the treatment of COPD, the need remains for additional therapies. The majority of diagnosed COPD patients largely remain under-treated in the US. As such, patients and physicians are always looking for new treatment options, and it will benefit the COPD community to optimize options for maintenance treatment of COPD.

Boehringer Ingelheim is committed to working with the regulatory authorities to make olodaterol available for the appropriate COPD patients in the U.S.

How much of a burden does COPD place on patients’ lives even with usual care?

COPD includes chronic bronchitis and emphysema. This disease makes it harder to breathe because less air is able to flow in and out of the lungs. As many as 26 million Americans may have COPD – even those who haven't smoked in years – and nearly half of them remain undiagnosed. COPD is the third leading cause of death in the United States. It kills one person every four minutes in the United States.

Common symptoms of COPD include shortness of breath and coughing with or without excess mucus.

What do you think the future holds for COPD treatments? How does Boehringer Ingelheim plan to contribute to this vision?

Leveraging the company’s cutting edge science and leadership in COPD, BI is researching new treatment approaches where needs persist. It is the company’s goal to make a difference in the lives of people living with COPD. We remain committed to lung health and building on our respiratory portfolio that has helped millions of patients around the world with COPD breathe better over the past decade.

Boehringer Ingelheim is currently studying a once-daily fixed-dose combination (FDC) of its investigational LABA, olodaterol, and its once-daily, long-acting anticholinergic tiotropium. The TOviTO^® Phase 3 clinical trial program for the fixed-dose combination of tiotropium + olodaterol (TIO+OLO FDC) delivered via the Respimat^® inhaler is underway to evaluate the potential of TIO+OLO once-daily FDC in the treatment of patients with COPD.

The TOviTO^® program consists of several Phase 3 studies. These include TOnado 1&2, the two pivotal registration studies, which are multi-centred, multi-national, randomized, double-blind, parallel group studies enrolling a total of 5,000 COPD patients across the spectrum of disease severity from GOLD Stage II to GOLD Stage IV at more than 500 trial sites in approximately 40 countries.

In addition to evaluating the effects of tiotropium plus olodaterol FDC on lung function, the TOviTO^® program is also focused on the evaluation of other important clinical outcomes that reflect the daily life of patients with COPD.

Where can readers find more information?

For more information please visit www.us.boehringer-ingelheim.com.

About Dr. Tunde Otulana

Dr. Tunde Otulana has been the Sr. Vice President, of Clinical Development and Medical Affairs since May 2013 and the Vice President, Clinical Development and Medical Affairs for Respiratory since December 2011 at Boehringer Ingelheim Pharmaceuticals, Inc.

A practicing pulmonologist, from 1997 to 2011 Dr. Otulana served as the Senior Vice President and Chief Medical Officer at Aradigm Corporation, Hayward, California and also at Aerovance Inc., Berkeley, California.

From 1991 to 1997, Dr. Otulana was Medical Officer and Clinical Team Leader in the Division of Pulmonary and Allergy Drug Products of the US FDA.  He led FDA’s review and approval of major asthma.  COPD and allergy drugs currently marketed in the US as well as in major FDA initiatives and special projects on pulmonary drugs. 

Since leaving the FDA, Dr. Otulana has served on the Agency’s Anesthesiology and Respiratory Therapy Devices Advisory Committee for four years ending November 2005. 

He is currently a member of the United Nations Environmental Program (UNEP) Aerosol Technical Options Committee charged with overseeing the phase-out of CFCs under the Montreal Protocol.  He also currently serves on the Editorial Board of the Journal of Aerosol Medicine and he is a Peer Reviewer for Chest.

Dr. Otulana obtained his M.D. degree at University of Ibadan, Nigeria and completed residency training in Internal Medicine at the University College Hospital, Ibadan and fellowship in Pulmonary Medicine at Addenbrookes and Papworth Hospitals, Cambridge, England and at Howard University Hospital, Washington, DC.  He is an author on many original scientific publications.