There is new class of treatment in development for Chronic Obstructive Pulmonary Disease (COPD). What makes this drug so interesting is that it is a treatment that uses a combination of two distinctive modes of action. Specifically, the COPD therapies are a combination of a long acting beta agonist (LABA) which dilates airways and a long acting muscarinic antagonist (LAMA).
What is Chronic Obstructive Pulmonary Disease?
COPD is the collective name for a number of diseases that all share a characteristic of having restricted breathing. These conditions include emphysema, chronic obstructive airways disease and chronic bronchitis. The principal cause of it is smoking, which ultimately causes lung inflammation. In time this inflammation causes the walls of the lungs to get thicker and the lungs lose suppleness.
A key distinction between COPD and Asthma is that, with COPD, a bronchodilator is typically the first line treatment followed by a corticosteroid. In Asthma, it is the other way around. Many treatments work for both diseases, but COPD treatments are taken more frequently.
Long Acting Muscarinic Antagonists
The first LAMA on the market is Boehringer Ingelheim's blockbuster COPD treatment Spiriva (tiotropium). According to PJ Barnes et al
"Clinical studies with inhaled tiotropium bromide confirm that it is a potent and long-lasting bronchodilator in COPD and asthma. Furthermore, it protects against cholinergic bronchoconstriction for > 24 h. This suggests that tiotropium bromide will be a useful bronchodilator, particularly in patients with COPD, and may be suitable for daily dosing."
Spiriva was launched in 2002 and rapidly became the gold standard in COPD treatment. Therefore, according to Dramane I Laine, LAMA treatments can be seen as strong candidates for combination therapies.
Long Acting Beta Agonists
LABAs are also bronchodilators but they have different and complementary modes of pharmacological action. This makes them ideal for combination therapy with LAMAs. Two of the best known LABA treatments are GlaxoSmithKline's salmeterol and formoterol which is marketed by many companies. Novartis has Indacaterol on the market in Europe (more on that later) but it is only approved for COPD, unlike salmeterol and formoterol which are also approved for asthma.
Combination Drugs in Development for Chronic Obstructive Pulmonary Disease
Vectura has a compound in development in their clinical pipeline which is set to become only the second single agent LAMA on the market. This compound is called NVA237 (glycopyrronium bromide) and is currently in Phase III FDA clinical trials. Final results are due in 2011 and the company would hope to make an NDA in 2011.
Vectura's plan is to combine their compound (NVA237) with Novartis' Onbrez (indacaterol), which is a LABA already on the market in Europe. This combination is called QVA149 by Vectura. Indeed, Vectura are already in Phase III trials with QVA149 and results are due in 2012. It should be noted that Novartis is a major partner of Vectura and they have a few key development programs in place for Asthma and COPD. Vectura is a specialist manufacturer of inhaler devices and also has its own compounds in development. Vectura expects NVA237 and QVA149 to be launched in 2012 and 2013 respectively
Another company with a LAMA/LABA combination is GlaxoSmithKline which has GSK573719 and GW642444 in clinical trials for COPD. Furthermore, Pearl Therapeutics has a LAMA/LABA combination in Phase IIb.
Barnes PJ, Belvisi MG, Haddad EB, O'Connor B"Tiotropium bromide (Ba 679 BRR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. Life Sciences, Volume 56, Issues 11-12, February 1995 pages 853-859
Laine, Dramane I "Long-acting muscarinic antagonists for the treatment of chronic obstructive pulmonary disease" Expert Review of Clinical Pharmacology, Vol 3, No 1, pages 43-53, January 2010
Vectura, Company RNS, 21 Oct 2010