AstraZeneca now led by science, not commercial milestones, says R&D head

AstraZeneca has turned its back on a commercially-led approach in favour of a ‘science first’ strategy, according to its head of drug development.

Mene Pangalos, AstraZeneca’s executive vice-president of Innovative Medicines and Early Development talked frankly about the firm’s long-running pipeline problems at yesterday’s Economist Pharm Summit.

The Anglo-Swedish firm has produced an extraordinary run of late-stage failures over the last decade, which has seen it fall to the bottom of big pharma’s R&D productivity league.

Drafted in from Pfizer in 2010, Pangalos now says AstraZeneca has addressed the cultural and strategic roots of the problem.

Pangalos said AstraZeneca had been “very much a process-led organisation” which incentivised its scientists to hit milestones for numbers of molecules in development, rather than on the quality of the science.

He said the organisation he joined in 2010 was focused on putting as many molecules into clinical development as possible, but that these were often poor quality. Around 50% of them were ‘back up’ molecules, artificially inflating the size of the firm’s clinical pipeline.

“In 2010, if you looked at the number of candidates we put into the clinic, we’d be one of the leaders – but if you looked at how many we actually launched, we’d be one of the worst performing,” he said.

He said AstraZeneca has now changed its focus, moving from “milestone seeking behaviour” to “truth seeking behaviour” where scientists are asked if they truly believe an investigational drug is destined to be a differentiated medicine, meeting an unmet clinical need.

He says this switch has produced very different conversations and behaviour within the company: “It takes quite a long time to change a culture, but I think we have changed it.”

Pangalos is not the first leader to reflect on the follies of R&D activities based around meaningless milestones or commercial targets – Sanofi’s Chris Viehbacher has also remarked on how process-driven decisions can undermine the scientific excellence which pharma depends on.

Pangalos –who formerly served in senior roles at Pfizer, Janssen and Bristol-Myers Squibb before joining AstraZeneca – says commercial pressures have distorted R&D priorities across the industry.

“I’ve seen many companies – including AstraZeneca – making poor decisions based on the commercial organisation telling you if you change your target indication that will make it a $2 billion product” he said. He added that this frequently ended in the science being led astray, with the wrong dosing schedule or the wrong patient population being used.

Addressing the ‘Net Present Value’ (NPV) metric commonly used to rate a molecule’s commercial potential, Pangalos said one of his former chief executives had confided:

“There is only one thing I can tell you about NPVs – they are always wrong. They are either too high or too low.”

The arrival of Pascal Soriot as AstraZeneca’s chief executive in 2012 has also been a major turning point, with the new leader cutting back its R&D operations even further in order to focus on core areas of research he believes the firm can compete in.

The company also unveiled plans to close its historic R&D base near Manchester in the UK and move south to Cambridge. The relocation will put AstraZeneca in closer proximity to a network of world-class academic researchers and biotech scientists, mirroring similar R&D development hotspots globally, such as its US namesake, Cambridge, Massachusetts.

The move to Cambridge will be complete by 2016, by which time the firm hopes to see some good news emerging from its pipeline.

One drug in development is notable for having been written off as a failure only for AstraZeneca to have second thoughts on its potential – on the insistence of its scientists.

Olaparib is a potential first-in-class in the ‘PARP inhibitor’ class of cancer medicines, and is now being developed for ovarian cancer. The drug was brought back into the fold after AstraZeneca’s scientist found it could help a sub-group of patients with the BRCA mutated variant of the disease.


A history of… AstraZeneca


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