LeadDiscovery - PharmaNewsBytes European Respiratory Society

News on asthma therapeutics presented at the European Respiratory Society: From 1980 to 1996, the number of Americans afflicted with asthma more than doubled to almost 15 million, with children under five years old experiencing the highest rate of increase. The steady rise in the prevalence of asthma constitutes an epidemic, which by all indications is continuing. Even if rates were to stabilize, asthma would continue to be a profound public health problem, each year responsible for 9 million visits to health care providers, over 1.8 million emergency room visits, and over 460,000 hospitalizations. As well as placing a considerable burden in terms of direct medical costs, asthma is one of the leading causes of work or school absenteeism.

Paralleling the dramatic growth in its incidence, asthma is driving one of the most rapidly growing global therapeutic markets. The impact that increased incidence is having on therapeutic market values is further increased by a considerable degree of under-treatment of asthma. Global revenue for 2001 from asthma therapies has been reported by some to be as high as $11.7 billion and up until recently annual growth rates of 10-15% have been reported.

In terms of numbers and health care expenses the chronic obstructive pulmonary diseases (COPD), chronic obstructive bronchitis and emphysema, are event more serious than asthma. World-wide, 600 million people suffer from these disease with some three million dying as a result each year. COPD is caused by chronic respiratory inflammation, proteolytic breakdown of airway tissue and consequent loss of elastic recoil in the lungs. This serious healthcare problem is paralleled by global sales of around US$2.8 billion which will increase in value significantly over the next decade. This will be driven by the aging population, new approvals and increased awareness.

Since the anti-asthmatic market is well served by existing therapies, such as the beta2-agonists and corticosteroids which can treat 95% of asthma patients competition within the anti-asthmatic market will grow increasingly intense. Consequently, to attain commercial success, pipeline products need to offer significant advantages over currently marketed therapies. In stark contract to the situation for asthma, therapeutic options for the treatment of COPD are limited and this represents an unmet market.

In the short-term the lack of effective oral therapies in the pipeline for both asthma and COPD means that inhalation will remain the primary mode of delivery. Advair, GlaxoSmithKline's blockbuster was initially approved as an asthma therapeutic but was used off-label for the treatment of COPD. However Advair, a combination of the corticosteroid fluticasone and the beta2-agonist bronchodilator, salmeterol has now been approved for the treatment of COPD which will see prescribing rates rise above off-label levels contributing to growth in the market. The asthma/COPD market will increase by 35% to over $18 billion by 2011 largely due to the success of inhalation therapies.

Although the $3.9 billion in Advair revenue dwarfs its nearest competitor, AstraZenecca's Symbicort (annual sales of $549 million) the annual meeting of the European Respiratory Society in Glasgow heard how GlaxoSmithKline's dominance of respiratory medicine is being challenged by a raft of new drugs.

The looming threat to Advair and negative sounds coming from analysts resulted in shares in GSK, which generates 21% of its sales from respiratory drugs, falling 1.6%. Analyst Anthony Colletta said he had reduced his forecast for GSK sales in 2010 by $1.1 billion due the challenge posed to Advair by AstraZeneca Plc's Symbicort and two new therapeutics for COPD, Spiriva and Daxas.

At the meeting AstraZeneca presented new data that it said reinforced the benefits of Symbicort over Advair and which analysts believe will strengthen the product's appeal when it finally goes on sale in the United States. Symbicort, while widely available in Europe, is not yet approved in the US. But a filing for marketing approval is expected to be submitted to the FDA in the first half of 2005. Analysts at Lehman Brothers said Symbicort would be a key mid-term focus for management and investors in coming months and would be in the spotlight at AstraZeneca's annual business review day on October 6.

Like Advair, AstraZeneca's drug combines a bronchodilator for short-term asthma relief with a corticosteroid to treat inflammation, but patients are able adjust their dose of Symbicort according to how they feel. That flexibility has prompted rapid take-up in Europe, where the drug has captured more than a quarter of the market within three years. By 2010 Dresdner expects Symbicort to rake in $3.1 billion, significantly closing the gap on Adavir which is forcast to be generating $7.7 billion.

Providing further competition to Advair, Boehringer Ingelheim's recently launched anticholinergic Spiriva is the first specific drug for COPD and analysts forecast sales of $3.3 billion in 2010. PDE-4 inhibitors will be the next novel drug class to reach the respiratory market, with the launch of roflumilast (Daxas) expected to generate sales of $2 billion [more on this story]

Further news from European Respiratory Society emerged surrounding Novartis' Xolair which was reported to effectively control even very severe cases of asthma.

This new data will be used by the Swiss healthcare group to strengthen its case with European regulators for the drug to be approved as a treatment for people with uncontrolled, and sometimes life-threatening, asthma, a sub-type of this conditions that is largely unmet. A 419-patient study showed that Xolair reduced the rate of clinically significant asthma attacks by 26% during 28 weeks of treatment. Xolair, the first biotechnology treatment for asthma, was developed by Novartis, US biotechnology group Genentech and Tanox Inc and was approved in the United States last year making it the first biologic to be approved for asthma. It was filed for EU approval in July. Xolair is a monoclonal antibody that works by blocking IgE thus treating the underlying cause of asthma triggered by allergies rather than the symptoms that inhaled corticosteroids address. However, it is less convenient then inhalers because the drug has to be injected. In the US, it is approved for treating moderate to severe asthma but Novartis is seeking approval in Europe for a narrower use among patients worst affected by asthma. Around 300 million people in the world have asthma, of whom an estimated 15 million have severe or life-threatening forms of the disease. Xolair generated US sales of $30 million in the first quarter of this year [more on this story]

Following the success of Xolair a number of other biotechs have focused on the development of antibody therapeutics in the respiratory tract arena. On Sept 8 one such company, Cambridge Antibody Technology, announced that it will be starting a Phase I clinical trial of CAT-354, a human anti-IL-13 monoclonal antibody, which is a potential treatment for severe asthma.

IL-13 is one of the molecules singled out as a target for future asthma therapeutics in LeadDiscovery's recent report "Asthma Therapeutics: New treatment options and emerging drug discovery targets". The Phase I trial is a placebo-controlled, rising single intravenous dose study of CAT-354 and will take place in the UK at the Marix Drug Development Clinical Research Centre. The objectives of the trial will be to study the safety, tolerability and pharmacokinetics of CAT- 354. Patient enrolment is expected to commence shortly and the results of the trial are likely to be available during the second quarter of 2005. Dr. David Glover, CAT's Chief Medical Officer, comments: "The initiation of this clinical trial represents a further milestone in the development of CAT as a biopharmaceutical company. CAT-354 is the fourth human monoclonal antibody that we have taken into clinical trials ourselves and makes a total of 11 human antibody drug candidates discovered using our technology that have entered clinical development. We are very optimistic about CAT-354 as a potential treatment for severe asthma." [more on this story]

Pharma NewsBytes features selected press releases recently featured on DailyUpdates and offers the reader a leisurely stroll through the past few weeks of activity from within the pharmaceutical industry.