Developments in treating asthma

May 3 is World Asthma Day. Clare Bellingham looks at recent developments in treating asthma

World Asthma Day is on May 3. This year, the National Asthma Campaign is organising a web-based event. People with asthma are invited to log on to the charity's website (www.asthma.org.uk) where an asthma nurse will be online during the day to answer queries.

One question is likely to be about the risks of being exposed to smoke from pyres used to burn foot and mouth carcasses. The smoke contains pollutants, including dioxins. The Department of Health advises that people with asthma living near pyres should stay away from the fires and keep all windows and doors shut.

Recent studies have shown that few patients with asthma are receiving adequate treatment. Last year, a study of nearly 3,000 people with asthma found that only 5 per cent were receiving treatment that met all the criteria for asthma control recommended by guidelines. Over a third of children and half of adults reported daytime symptoms at least once a week, with asthma-related sleep disturbances in over a quarter of all patients (European Respiratory Journal 2001;16:802). More recently, a need for more effective treatments for patients with difficult-to-treat asthma was identified by a survey of 50 British chest consultants. The survey, conducted by ISIS/Novartis, found that 84 per cent were not satisfied with the current treatment options available to them.

So what treatments are around the corner for asthma?

Targeting allergy

Extrinsic, or allergic, asthma is mediated by immunoglobulin E (IgE) and is triggered by allergenic factors, such as the house dust mite. Intrinsic asthma is not IgE-mediated and is triggered by non-allergenic factors, such as chemical irritants. According to the National Asthma Campaign, allergic asthma occurs in 80 per cent of children with asthma and more than half of adults with asthma.

An anti-IgE drug, omalizumab (Xolair), is expected to be launched at the end of this year, or possibly the beginning of 2002. At a press conference earlier this month organised by Novartis, the drug's manufacturer, Dr Michael Rudolf, respiratory consultant, Ealing Hospital, and honorary senior lecturer, Imperial College, London, said that targeting IgE represented an “entirely new way of treating asthma in the future”.

Exposure to an allergen, such as the dust mite, stimulates the production of IgE antibodies which trigger the release of mediators from mast cells (degranulation). The released mediators cause the local inflammatory response. Professor Tony Frew, allergy specialist, Southampton General Hospital, told the press conference that targeting IgE blocks the process “further upstream” than current therapies.

Novartis hopes that omalizumab, which has to be given by injection once or twice a month, will be licensed for adults and children aged over 12 years with allergic asthma but reserved for people with severe asthma. The company believes that omalizumab will fit into steps four to five of the British Thoracic Society guidelines (see BNF, no 41, p132) on management of asthma. A spokeswoman for Novartis said on April 20 that the major advantage of omalizumab over current therapies was that it helped to reduce the number of attacks because it worked earlier in the inflammatory cascade for asthma. Clinical trials have shown that it reduces asthma attacks by 35 per cent, she said.

Dr Martyn Partridge, the National Asthma Campaign's chief medical adviser, commented on April 24: “This therapy represents a new approach to the management of asthma. While the new drug will only be needed by a relatively small group of people and its method of administration is not easy, it is a welcome new product which increases our choices in the treatment of people at the very difficult end of the spectrum of asthma.”

Another drug being developed to target the inflammatory process in asthma is mepolizumab. It is a monoclonal antibody against interleukin-5, an inflammatory mediator, and is being developed by GlaxoSmithKline. Mepolizumab is in early phase II trials.

Also in development at GlaxoSmithKline is cilomilast (Ariflo), a phosphodiesterase-4 inhibitor. According to the company, cilomilast reduces bronchoconstriction, inflammatory processes and sputum production associated with both asthma and chronic obstructive pulmonary disease. It is in phase II clinical trials for asthma, and phase III for COPD, and the company expects that it will become available in 2003.

Other companies are concentrating on existing therapies. Aventis, for example, is developing a new inhaled corticosteroid, ciclesonide. It is currently in phase III trials.

Improving delivery

A new inhaler device in development is an electronic atomiser called TouchSpray. The device consists of a thin foil membrane that is made to vibrate by a battery-powered electronic device. As the surface of the foil comes into contact with a solution or suspension of drug, the liquid passes through small holes in the foil. This action results in the solution of drug dispersing to form an aerosol plume of fine droplets.

The advantages of TouchSpray are that the output rate and droplet size can be precisely controlled and targeted, according to Dr Jonathan Smart, head of commercial developments at Odem, the company marketing the device. This means that it gives excellent drug delivery to the lungs, he said. The technology has applications in pulmonary, nasal and systemic drug delivery. Solutions and suspensions that can be made into an aerosol could potentially be delivered with this device, including proteins and peptides, such as insulin. Another advantage of TouchSpray is that it is propellant-free. Dr Christopher Graeme-Barber, marketing director of The Technology Partnership, the company that developed the device and is now a founding partner of Odem, said that TouchSpray technology could be expected to reach the market within the next few years.

The research approach at 3M Health Care is concentrating on delivery of small particles. There is a growing body of evidence that suggests that smaller particle size and more effective delivery can improve deposition in the small airways of people with respiratory disease, according to Dr Richard Spiers, medical director, 3M. “When developing Qvar, we recognised the potential to improve current delivery devices and lung deposition, which has resulted in the ability to lower the inhaled steroid dose. By targeting 3M's research on the small airways, we hope to make a significant contribution to the future improvement in asthma care,” he said.

Asthma facts

• Over 3.4 million people in the UK have asthma
• Approximately one in seven children (aged between two and 15 years) in the UK has asthma currently requiring treatment, equivalent to over 1.5 million children
• At least one in 25 adults (aged over 16 years) in the UK has asthma currently requiring treatment, equivalent to over 1.9 million adults
• Up to 5 per cent of people with asthma in the UK have “difficult” asthma that cannot be controlled with maximum doses of asthma medication

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Clare Bellingham is on the staff of The Pharmaceutical Journal