Bacterial resistance to antibiotics is a global health threat. Creative collaboration is the key to successfully meeting the challenge.

Thursday, 17 November 2011

Seventy years ago, the discovery of antibiotics revolutionized the treatment of bacterial infections and saved millions of lives. It seemed the battle was over. But now there is a renewed challenge. The bacteria are fighting back – constantly evolving and mutating in a bid to survive - and many are successfully developing resistance to previously effective antibiotics.

This kind of bacterial resistance threatens to put global health at serious risk. For example, hospital-acquired infection causes around 90,000 deaths in the US and 25,000 deaths in Europe each year. In China, over 5 % of hospital patients contract hospital-acquired infections and face one of the highest rates of antibiotic resistance in the world. The highest levels of resistance are in developing countries, where one study found that that the rate of neonatal hospital-acquired infections was up to 20 times higher than in the developed world.

Finding new antibiotics that will be effective against bacterial resistance is not impossible, but it’s a complex and challenging area of research. It’s also an area that has not been a primary focus for the pharmaceutical industry in recent years due to a variety of contributing factors: the misperception that new treatments were not needed, the lack of financial incentive (antibiotics generally represent a relatively low return on investment), and the demanding regulations for drug development.

What are we doing about it?

AstraZeneca is one of the few large pharmaceutical companies to have continued to invest in antibiotic research during the last 10 – 20 years and today. We have leading capabilities in bacterial genomics and biochemistry and two antibiotics for hospital-acquired infections in our range of marketed medicines, including a leading carbapenem anti-bacterial effective against multi-drug resistant (MDR) bacteria. We are now expanding our efforts to improve our pipeline of new products that will meet the growing need for new ways of treating MDR bacteria. We recently boosted our capabilities with a new facility in Boston US, representing a $100 million investment in anti-bacterial research.

In October 2011 we announced with our partner, Forest Laboratories, that Ceftazidime/avibactam (CAZ-AVI) will enter phase III trials to investigate efficacy in treating hospitalised patients with serious Gram-negative bacterial infections due to MDR bacteria. The range of infections to be studied includes Complicated Intra-Abdominal Infections (cIAI) and Complicated Urinary Tract Infections (cUTI). CAZ-AVI combines a broad-spectrum cephalosporin (ceftazidime) and a novel beta-lactamase inhibitor (avibactam, formerly NXL104) to overcome antibiotic-resistance and thus treat the increasing number of infections resistant to existing therapies.

Creative collaboration is key

No single company can win the battle on their own. We partner with other research companies to accelerate the delivery of next generation antibiotics. For example, last year we licensed from Forest Laboratories a new compound in development that has shown promise against a number of infections and multi-drug resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Through this collaboration, we will contribute our development, commercial and regulatory expertise to bringing this treatment to market. In a further collaboration with Forest Laboratories, we also recently acquired Novexel, a private infection research company which has two novel-action antibiotics in late stage development, both of which are demonstrating potential in treating infections that are resistant to existing therapies. CAZ-AVI (see above) is one of these compounds and are working with Forest Laboratories to combine our complementary skills to speed the progress of these compounds from development through to commercialisation.

Working in public and private sector partnerships

Successfully tackling drug resistant infection in the future will also depend on combining the strengths of both private and public sectors to address the full range of scientific, financial and regulatory obstacles to managing this significant threat to public health. Public-private sector partnerships can be challenging and require us to be open about the different drivers and perspectives we bring, but the ultimate goal is a common one – improving health. Together, we can make a greater contribution to reaching that goal.

One example of the potential of such partnerships is in the fight against tuberculosis. Today, multi-drug resistant TB affects half a million people annually, takes two years to treat, and is cured in only half of all cases. Overall, TB still claims 5,000 lives every day. To accelerate the development of new treatments, a major collaboration led by the Bill and Melinda Gates Foundation, the TB Alliance, and the Critical Path Institute has brought together AstraZeneca and other pharmaceutical companies, government agencies, non-government organisations, donors, advocates and academics. This initiative is exploring creative funding mechanisms and support for late-stage clinical trials. Today, there are nine promising TB compounds from at least six antibiotic classes in development, including one compound from AstraZeneca. Our dedicated TB research facility in Bangalore, India is playing its part. The initiative is also working with regulators to reduce the length of time it takes to approve new TB drugs (without of course compromising on patient safety). This type of collaboration has created real potential for a major step forward in the treatment of TB and offers a model for other multi-stakeholder partnerships working to improve health outcomes in the future.

Another area where collaboration is playing a vital role is in tackling malaria, which claims over one million lives every year. AstraZeneca and Medicines for Malaria Venture, a not-for-profit public-private partnership, are working together to identify novel candidate drugs for the treatment of malaria. We are giving MMV access to an extensive library of “banked” compounds. MMV will screen this library to identify compounds which show promise as a treatment for malaria, including drug-resistant strains. We will then help, through our infection research facility in Bangalore, to bring the new drugs to market.

Looking beyond medicines

Importantly, the job isn’t done once new and effective treatments are delivered. One enabler of increasing bacterial resistance has been the wide use of antibiotics in recent years. Slow diagnostics meant that doctors frequently treated patients with broad-spectrum antibiotics while waiting for test results. To address this concern, significant effort has been invested in recent years to generate diagnostic tests which could guide antibiotic use. In addition, in countries where antibiotics are available over the counter, people have been self-prescribing and using antibiotics widely and inappropriately. Which is why, when a new treatment is found, we will work with regulators, healthcare professionals and others to make sure that prescribers and pharmacists have all the information they need to make sure that antibiotics are used appropriately.

Making a real difference in the fight against resistant disease

The spread of drug-resistant bacteria is becoming a serious threat to health around the world. In the past 30 years, only two new classes of antibiotics have been introduced. A global effort is required to find urgently needed new treatments. AstraZeneca is committed to playing its part by applying our skills and experience in infection research and by combining forces with others to overcome the challenges holding back the discovery of new antibiotics.

LabTalk is AstraZeneca’s science-focused blog where you can hear from scientists, researchers and academics discussing novel ideas, research and innovation.

banner_az_THM 29 September 2015

PI3K inhibition: the pathway to next-generation respiratory medicines?