Asthma/COPD combination products here to stay

Sufferers of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) are breathing easier due to being increasingly treated with fixed dose inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) combination therapies.

The appeal of these combinations is three-fold: improved patient compliance, simplified disease management and the certainty of bronchodilator and steroid co-administration. Until recently, there were only two such combination inhalers available: GlaxoSmithKline's Advair (marketed in as Seretide), which is generated sales of just over $4.9 billion in 2005 across the seven major markets, and AstraZeneca's Symbicort.

Current battle

With 42 million asthma sufferers and 28 million COPD sufferers, the asthma/COPD treatment market was worth around $17 billion in 2005, and is dominated by the ICS/LABA combination class, which accounted for 32% of sales ($5.5 billion). Datamonitor expects this market share to grow to $12.2 billion in 2015, with the entry of up to three new products onto the market. GSK's Advair was the first product in this class to reach the market in 1999 and has been dominating it ever since. AstraZeneca launched its combination product, Symbicort, in in 2001 and received the FDA's approval in July 2006.

Realizing the importance of and difficulty of ensuring patient compliance, AstraZeneca has sought to differentiate its product from Advair through an alternative, more patient-empowering treatment approach dubbed SMART (Symbicort Maintenance and Reliever therapy). This concept uses Symbicort to provide a stable dosing regime, just like Advair, but with the additional ability to increase the dose (i.e., the number of puffs) during symptom exacerbation, instead of using short-acting rescue bronchodilators like Ventolin.

Combination advantages

Non-compliance is a significant problem in the treatment of asthma and COPD, especially in later stages of disease. These patients have a multitude of drugs to deal with on a daily basis and are often confused on their exact treatment regime. Furthermore, patients tend to forget to take their ICS medication because, unlike a bronchodilator, it does not give them immediate relief.

Since the regular use of anti-inflammatory drugs is key to treating the underlying disease, the combination drug's advantage is the automatic intake of the ICS alongside the bronchodilator, making disease management easier for both patients and physicians.

Another advantage of these combination drugs is that patients always inhale their LABAs in combination with an ICS. Recent concerns regarding the dangers of LABA monotherapy in the treatment of asthma led to the 1996 Salmeterol Multicenter Asthma Research Trial (confusingly also called SMART), which investigated salmeterol (a type of LABA) in the treatment of asthma. A possibly increased mortality rate in certain subgroups of asthma patients using this drug was found, leading to safety warnings on LABA drug labels.

Datamonitor believes that very few physicians prescribe LABAs as monotherapy and that non-compliance is the main reason for patients using LABAs without ICS's. A combination of these two drug classes in a fixed dose combination would therefore go a long way in dealing with this issue.

The third combination product on the market is Chiesi's Foster (beclometasone/formoterol), approved in in September 2006. The critical factor for a successful launch of this drug will be its price relative to Advair and Symbicort. Datamonitor estimates that Foster will generate sales of around $330 billion in 2015, depending on the pricing-strategy Chiesi will choose.

More to come

The outlook for this market shows even more competition in the future, with several novel ICS/LABA combination products set to enter the market in the coming years. The first and most important will be GSK's Super Advair, expected to be launched in 2010. This product, while based on two completely new drugs, can be viewed as essentially a once-daily reformulation of Advair.

A lot is riding on the timing of Super Advair's approval as Advair's patent expires around the same time, in May 2010. GSK needs to switch as many patients as possible to Super Advair before the entry of Advair generics. Assuming this and that it offers significant advantages over the current Advair, GSK should be able to retain most of its ICS/LABA combination drug sales.

The expected launch of Altana and Sanofi-Aventis' Alvesco Combo (ciclesonide/formoterol), forecast for the first half of 2011, is the next significant event in the ICS/LABA combination drug class, as the product appears to have a very good competitive profile. Ciclesonide provides important safety advantages over existing corticosteroid treatments, especially in patients requiring high-dose ICS.

Uncertain future

However, this product's future remains uncertain because ciclesonide is still not approved in the and European regulators only licensed a lower than expected maximum dose of 160mcg once-daily. Although Altana's previous failure to gain approval for Alvesco's possibly more efficacious 320mcg dose once-daily does not spell the end of the development of a fixed-dose combination product, if Altana cannot get the higher dose approved, it would undermine the marketing concept of Alvesco being a safer steroid.

SkyePharma/Kos Pharmaceuticals' fluticasone/formoterol and Schering-Plough/Novartis' mometasone/formoterol are ICS/LABA combinations currently in development. They are expected to be launched in mid and late 2010, respectively.

A more exciting combination however, is Schering-Plough/Novartis' mometasone/QAB-149 (indacaterol). Currently still in preclinical development, this drug has the potential to combine once-daily dosing with a flexible dosing regime (like SMART) and could therefore be Super Advair's biggest threat, if launched successfully.

With new dosing regimes, competitive pricing and upcoming generic entry, the ICS/LABA class is facing challenging times. The key players in this field will need to differentiate their products carefully from their competitors' in order to generate and maintain sufficient traction, and with the first generics expected from 2010, pricing pressure will only rise.

Related research:

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