GlaxoSmithKline licenses Theravance respiratory program

The program is the third respiratory program licensed by GSK from Theravance. Using the principles of multivalent drug design, Theravance discovered a unique series of long-acting inhaled bronchodilators that are bifunctional; one molecule functions as both a muscarinic receptor antagonist and a beta2 receptor agonist. These compounds are under investigation for their potential to treat patients with chronic obstructive pulmonary disease (COPD) and possibly asthma.

Asthma is a highly prevalent chronic disease estimated to cost at least $13 billion (€10 billion) in the US alone each year. In the UK, there are four times as many people with asthma than with diabetes. The number of patients with asthma in the seven largest pharmaceutical markets is set to rise from 51.4 million in 2003 to 62.4 million in 2013, stimulating greater demand for cost-effective asthma therapies.

This move is could be seen as GSK's response to the current situation. >GSK​ needs to expand the pipeline of its leading franchise, which is forecast to demonstrate declining sales and negative growth in the next five years.

Although GSK's respiratory sales increased from $6.5 billion in 2001 to almost $8.1 billion in 2004, the franchise's value is expected to drop from $8 billion in 2005 to $5.7 billion by 2010. Seretide/Advair is expected to show a revenue decline over the next five years from $4.9 billion in 2005 to $4.2 billion in 2010, accounting for 74 per cent of franchise sales at that point.

Dr Pat Humphrey, executive vice president of research at Theravance​, said: "We combined bifunctional activity and high lung selectivity to identify a potential medicine with greater efficacy and equal or better tolerability than single-mechanism bronchodilators. We designated TD-5959 our lead MABA compound in December 2004 and have been engaged in preclinical studies since then."​

"We also pursued this program because we believe this type of bifunctional molecule could serve as a basis for improved 'triple therapy' through co-formulation with another inhaled respiratory compound into a single product that could potentially deliver three complementary therapeutic effects for patients with respiratory disease."​

Under the terms of last year's agreement, Theravance could receive up to $252 million in upfront and milestone payments, if the program has both single-agent and combination products and certain milestones are achieved, in addition to royalties on sales of any MABA products commercialised by GSK.

Effective immediately, GSK will fund all future development, manufacturing and commercialisation activities for product candidates in this program in accordance with the terms of the strategic alliance between Theravance and GSK. The lead compound in the program is currently in the preclinical phase.

GSK should continue to expand the pipelines of its key respiratory, CNS and infectious diseases franchises with early and late stage programs licensed or acquired from the emerging biopharmaceutical world. Such a strategy offers a potentially vital means of gaining new compounds being developed in the biotech sector, which would benefit from having GSK's marketing and production muscle behind them.

Successful late stage licensing deals would be particularly useful as even getting new products to this stage of the developmental process is itself fraught with risk. Many analysts believe that GSK needs to be pro-active in its efforts to maximise the number of its products that reach market, ensuring that it boosts its revenues sooner rather than later.

Although many therapies are available for asthma and a growing number for COPD, reports from the National Institutes of Health indicate that these diseases remain major causes of death and disability. Seretide/Advair (salmeterol/ fluticasone) is the current market-leading medicine in this class with over $3.6 billion of sales reported by GSK in 2003. While the FDA has approved Advair for the treatment of asthma and COPD, it must be administered twice a day, which reduces patient compliance.

The alliance between GSK and Theravance is likely to be the start of many more. Smaller biopharma companies offer a fruitful means for the big players like GSK to broaden their portfolio of new drugs, and deals such as this are likely to become increasingly common in future.

At the start of this year, Pfizer and Rigel Pharmaceuticals entered into a collaboration to develop a novel class of compounds for the treatment of allergic asthma and other respiratory diseases.

The collaboration aims to further develop Rigel's preclincal small molecule compounds, which inhibit the IgE receptor signalling in respiratory tract mast cells by blocking the signalling enzyme Syk kinase.

The small molecules' mechanism of action causes them to bind to and inhibit Syk kinase, an intracellular target that regulates IgE receptor signalling in mast cells and thus prevent cellular activation and subsequent release of multiple chemical mediators.

However, unlike common allergy and asthma drugs that block only a single chemical mediator, Syk inhibitors block the major IgE dependent pathways in mast cells that trigger an allergic attack, potentially making Syk inhibitors more effective and comprehensive drugs.