AstraZeneca has received FDA approval for its combination asthma drug Symbicort, which will now enter a fiercely competitive market, to face not only GlaxoSmithKline's blockbuster Advair but also new combination drugs, which are expected to steal market share from 2010. However, as Datamonitor's Lisette Oversteegen explains, Symbicort's SMART approach could be key to overcoming these challenges.

The FDA has approved Symbicort (budesonide/formoterol) for the maintenance treatment of asthma in patients aged 12 and older. Symbicort has been on the market in Europe since 2000 – although available in a different device - where it was also approved for a pediatric and a chronic obstructive pulmonary disease (COPD) indication.

Symbicort is a fixed dose combination product containing an inhaled corticosteroid (ICS) and a long-acting beta2-agonist (LABA). The appeal of such a fixed ICS/LABA combination lies in its safety (the certainty that the LABA is always prescribed with an ICS), high patient compliance and simplified disease management. The fact that the leading drug class in the asthma/COPD market in 2005 was the ICS/LABA combination class clearly highlights a shift to such treatment regimens.

The only other fixed dose ICS/LABA combination product on the US market is GlaxoSmithKline's Advair (fluticasone/salmeterol), which is marketed as Seretide in Europe. This drug is approved for the maintenance treatment of asthma in patients aged four years and older and patients with COPD. It achieved sales of $3.4 billion in the US in 2005, showing that the ICS/LABA combination class is a profitable market to be in.

Early approval

AstraZeneca filed a new drug application for Symbicort in September 2005 and expected the process to take the average 18 months. The early approval within 10 months clearly took the company by surprise; its manufacturing facilities are not yet ready to supply the US market. This explains why Symbicort will not enter the market until mid-2007.

AstraZeneca had initially planned to launch Symbicort in the US using the dry powder Turbuhaler device, but development using this device was discontinued in 2001. Although AstraZeneca has successfully developed an alternative delivery device using metered-dose inhaler technology, the delay means that Advair, which was launched in the US in 2001, will have had a total of more than six years of market exclusivity by the time Symbicort reaches the American market.

The situation is going to be even more competitive in the future: there are several novel ICS/LABA combination products set to enter the US market in the coming years. The first, and most important, will be Super Advair, which is expected to be launched in the first half of 2010. Super Advair, while based on two completely new drugs, can be viewed as a once-daily reformulation of Advair. Timing of its approval will be crucial for GSK as Advair's US patent expires in May 2010. By switching as many patients as possible to Super Advair before the entry of generics (and assuming it offers significant advantages over Advair), GSK could retain most of its Advair/Super Advair sales.

Other contenders

The possible launch of Altana and Sanofi-Aventis' Alvesco Combo (ciclesonide/formoterol), expected in the first half of 2011, will take further share from the ICS/LABA combination drugs. Indeed, this product appears to have the best competitive profile. Ciclesonide provides important safety advantages over existing corticosteroid treatments, especially in patients requiring high-dose ICS. However, the future of this product is uncertain since Alvesco (ciclesonide) is still not authorized in the US.

European regulators only approved a maximum dose of 160mcg once-daily for Alvesco; Altana failed to gain approval for the higher and possibly more efficacious 320mcg dose. A US approval of the low dose of 160mcg once-daily for Alvesco would not spell the end of development of a fixed-dose combination product: lower doses of ciclesonide could still sensibly be used in a combination product given that the LABA has a synergistic effect. However, it would undermine the marketing concept of Alvesco being a safer steroid.

In contrast, approval at the 320mcg dose would give the ciclesonide franchise a vital boost by building sales momentum in the inhaled corticosteroid monotherapy market ahead of a possible launch of a combination product. Alvesco Combo's US sales could reach $550 million in 2015.

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

The SMART approach

Meanwhile, AstraZeneca is focusing its marketing efforts on Symbicort's adaptability for adjustable maintenance dosing, a treatment concept known as Symbicort maintenance and reliever therapy, or SMART. With the SMART approach, Symbicort is used to provide a stable dose therapy, like Advair, with the additional feature of a patient-controlled increase of the dose during worsening of symptoms. This will do away with the need for short-acting bronchodilators, such as salbutamol, as rescue therapy.

AstraZeneca originally submitted a regulatory application in Europe for Symbicort SMART dosing in November 2003 but withdrew it in November 2004 as a result of discussions during the mutual recognition process. On the basis of additional data from further ongoing studies known as COSMOS and SMILE, an EU mutual recognition variation procedure for SMART started again in September 2005.

If AstraZeneca decides to file Symbicort's SMART indication in the US as well, this treatment concept would be a key differentiating factor from Advair. Although there was debate among key opinion leaders interviewed by Datamonitor about whether this type of treatment is appropriate for all patient groups, the overall tenor was positive. It will be important for AstraZeneca to convince patients and doctors that SMART offers an advance in treatment strategy by allowing patients to increase their maintenance drug dose earlier and therefore reduce the number of exacerbations and hospitalizations.

Despite several delays and the danger of being pressurized by other novel ICS/LABA combination treatments from 2010 onwards, Symbicort could yet challenge Advair's US market leadership thanks to its key differentiating factor, the SMART concept. This will give AstraZeneca an advantage that may turn out to be the determining factor for Symbicort's success in the US, leading to predicted sales of $1.9 billion in 2015.

Related research:

 Commercial Insight: Asthma/COPD - ICS/LABA combinations continue to dominate priced $15,200
 Monoclonal Antibodies in Asthma: The choice between life and breath? priced $1,900
 Commercial Insight: Asthma and COPD - Get SMART priced $15,200

To order contact peter.barfoot@bioportfolio.com or telephone +44 1300 321501 or +1 415 680 2472 and a representative will get back to you.

You can also order on line at: http://www.bioportfolio.com/cgi-bin/acatalog/search.html