GSK targets autoimmune biologics

UK-based drug maker GlaxoSmithKline (GSK) is making a concerted push to become a world leader in the autoimmune inflammatory disease arena - an area of treatment that has been revolutionised by the emergence of biologic drugs. As well as focusing its internal research on the area, GSK recently signed seven drug development deals that could see the company release a suite of drugs to treat inflammatory diseases ranging from rheumatoid arthritis to lupus.

Doctors treating autoimmune diseases have traditionally had to rely on drugs such as steroids or NSAIDs (non-steroidal anti-inflammatory drugs), which can only reduce inflammation, rather than actually stopping the tissue damage as the body attacked itself.

The introduction of biological drugs that interfere with the disease pathway by binding to proteins involved in the inflammatory cascade, such as tumour necrosis factor (TNF), has in many cases enabled the diseases themselves to be targeted, and the inflammation and tissue damage caused by the diseases to be significantly reduced.

Biological therapies such as Johnson & Johnson’s Remicade (Infliximab), Amgen and Wyeth’s Enbrel (etanercept) and Abbott’s Humira (adalimumab) have proven extremely effective. According to Rachel Haynes, director of public affairs at the charity Arthritis Care, these new drugs have made an enormous difference to patients - so much so that people who would have been in wheelchairs without the drugs are able to lead active lives.

Biologic boost

Industry analyst Sylvia Miriyam Findlay from Frost & Sullivan says the number of autoimmune drugs available on the market is growing, and that the entry of biological drugs onto the market has significantly increased revenues in the area.

She estimates that in 2006 the market for rheumatoid arthritis therapies was worth some $36 billion (?25 billion), while the market for inflammatory bowel disease medication reached $16 billion, lupus drugs $12 billion and psoriasis products $6 billion. These markets are likely to continue growing as there is still a large unmet clinical need, and the number of patients with autoimmune diseases is growing.

GSK highlighted the disease area as one of the eight it would focus its research efforts on after Andrew Witty took over as the company’s chief executive in May 2008. Since then, GSK’s immuno-inflammation CEDD (Centre for Excellence in Drug Discovery) has signed co-development deals with Archemix, Biotica, CellZone, Dynavax, Galapagos, Regulus Therapeutics and Harvard Medical School.

’The strategic intent is to become the world leader in immuno-inflammation through a combination of internal and external research programmes,’ says Jose Carlos Gutierrez-Ramos, head of GSK’s immuno-inflammation CEDD.

This is an ambitious aim, given that in 2006 GSK did not even feature in the top ten players in the arena, which is currently dominated by Amgen, Johnson & Johnson, Pfizer, Novartis and Wyeth. The company has some catching up to do, as Findlay believes the market will see an influx of new drugs in the next six or seven years if the candidates currently in Phase II clinical trials make it to the market. 

According to Gutierrez-Ramos, GSK plans to achieve this rapid growth by conduct around 50 per cent of the research outside of the company - and more deals could well be announced during the coming year. 

’This business model adopted by GSK is sound and shows good foresight into the future dynamics of the autoimmune/inflammatory disease areas,’ Findlay told Chemistry World. ’GSK is likely to emerge as a leader in the inflammatory diseases market in the next eight to ten years,’ she adds.

Gutierrez-Ramos is certainly buoyant about GSKs prospects, and believes the company is entering the arena at just the right time. ’Immuno-inflammation is in a similar place to where oncology was five or six years ago; certain biological drugs have really opened up a way to increase our understanding of the key pathways - much like the biologics that told us that EGF [epidermal growth factor] pathways were important in oncology,’ says Gutierrez-Ramos. 

On trial

Pharmaceutical firms continue to be frustrated by the large number of drugs that fail during late stage clinical trials - after lots of time and money has already been spent developing them. Gutierrez-Ramos is looking to tackle this problem head-on by conducting more thorough Phase I trials that will gather more pharmacological data than is currently being collected. 

Rather than looking for the next blockbuster by targeting only the most common illnesses, these trials will be designed to test each drug’s mode of action, from which the disease each is best suited to treat will be identified.

’We are actually disease agnostic and have decided to focus on certain mechanisms that regulate the immune system that we believe are fundamental, and we will follow those mechanisms through molecular medicine studies into the indications that suit the mechanism best,’ says Gutierrez-Ramos. 

’We will not shy away from the smaller indications like sub-types of lupus or malignant autoimmune orphan disease - which traditionally are not a space that big pharmaceutical firms have focussed on,’ he concludes.

Matt Wilkinson