“New science for better decisions”

Effective risk assessment, failing drugs faster and improving productivity and cost-efficiency are becoming even more important to the pharmaceutical and biotechnological industry, which is now spending a walloping average €895 million on researching and developing a single new medicine. The pressure is on those charged with leading discovery.

“Right now, my main priority and focus is on filling AstraZeneca’s pipeline with quality compounds that have an increased likelihood of transitioning through the clinic and hopefully onto the market,” says Jan Lundberg, Executive VP and Global Head of Discovery at AstraZeneca.

Through key initiatives like its Discovery Medicine Programme, where bench scientists are working in close partnership with clinicians, AstraZeneca is improving both its disease knowledge and models. “Furthermore, through effective frontloading of safety and drug metabolism and pharmacokinetics (DMPK), we can make better decisions and weed out undesirable compounds much sooner in the R&D process, and in turn, improve both our speed and quality,” adds Lundberg.

Pharma R&D: an inherently risky endeavour

Whether a promising new compound fails in pre-clinical testing or in the final phases of clinical trials makes a huge difference. Hundreds of millions of euros may be lost. AstraZeneca experienced this with their potential blockbuster NXY-059, for treating stroke patients. It showed no efficacy and did not meet its primary outcome of a statistically significant reduction in stroke-related disability in Phase III clinical trials, which measured the treatment against a placebo. Have they since worked on more effective strategies to assess the risk of failure of candidate drugs in development?

“Pharmaceutical R&D is an inherently risky endeavour. But obviously we aim to mitigate those risks at all stages of our R&D process,” says Lundberg. “We are actively scrutinising every compound at every stage for preset quality criteria. It is about starting with the right disease mechanisms, creating molecules with the right properties, for example efficacy and safety, using the predictive disease models, and identifying and using biomarkers for early clinical effects and selection of the right patient subgroups and endpoints.”

Whether or not unsuccessful drugs can be weeded out earlier depends on the indication. The predictions from preclinical observations need to be confirmed in humans and for some indications, such as stroke, Lundberg believes large Phase III trials are still necessary to get conclusive outcome data.

To improve R&D productivity and cost-efficiency Lundberg refers to AstraZeneca’s ongoing initiatives to bring better, new medicines to patients faster. Examples of their efforts include their focus on disease areas with the highest future medical need, breaking science and the greatest opportunity for success, including cancer, infection, pain, COPD and diabetes.

“Furthermore,” Lundberg adds, “we are taking a long-term approach to expand our knowledge of validated disease mechanisms, such as thrombin inhibitors for anticoagulation and the treatment of thrombosis. Our expanding portfolio of biopharmaceuticals will also play an important role in improving the overall likelihood of success for the most important disease approaches.”

The vision

Improving productivity and cost efficiency is an obvious goal for Lundberg. However, he also believes that this must be done while delivering compounds of the highest quality. “This means that we want to have several chemical lead series to choose from and that we conduct rigorous early safety and DMPK testing before we ever nominate a candidate drug. We also need access to the best external science to influence our internal activities and to complement our own product opportunities.”

This means research collaborations such as the worldwide collaboration with Bristol-Myers Squibb to develop and commercialise diabetes compounds. Diabetes is a disease reaching almost epidemic proportions in many regions throughout the world and it is a particular area of scientific interest for AstraZeneca. The deal represents a significant step in delivering their externalisation strategy as it gives them access to two strategically important late stage compounds in an area of high, unmet medical need.

A robust portfolio

In the last two years, AstraZeneca has also made some important strategic partnerships and acquisitions including the acquisition of Cambridge Antibody Technology (CAT) and Kudos. With the acquisition of CAT, AstraZeneca is moving closer to fulfilling its biopharmaceuticals strategy with a vision to become a leading biopharma company. Lundberg: “We continue to build our biopharma capabilities through a variety of different activities and applications. These are taking place in the UK, Sweden and the US. Small molecule and biopharma opportunities are in many ways complementary, and provide us with a broader approach to achieve success with the best treatment opportunities.”

Jan Lundberg: Wants to see AstraZeneca expanding into the exciting arena of biopharmaceutical drugs

Moreover around 70 percent of medicines that eventually reach the market do not provide sufficient return to recoup their R&D expenditure. As a consequence, the return on investment is highly dependent on a limited number of successful products.