While the success rate in developing new disease treatments remains alarmingly low, a cadre of R&D executives from some of the world's biggest drug developers insisted at BIO that they've zeroed in on a number of ways to boost the chance a promising drug will actually reach patients.
Speaking during FierceBiotech's breakfast panel discussion on April 23 (moderated by FierceBiotech Editor-in-Chief John Carroll), they shared a broad consensus that smaller trials, trial design experimentation, wider collaborations, and intense spending discipline are some of the ways that can and have made a difference to their pipelines.
"What [the R&D process] needs is real discipline," said Martin Fitchet, chief operating officer for research and development at Johnson & Johnson's ($JNJ) Janssen Pharmaceuticals division. "We are trying to instill much more discipline in taking a fact-based approach in investing, to improve the concept. The downside of that, if it is a positive concept, you have to catch up quickly. But if you do that full-blown press for all early stage projects, you won't be able to afford the portfolio and you will still get a higher failure rate."
Some of the panelists said that rethinking how they approach clinical trials has made a difference. For Jose-Carlos Gutiérrez-Ramos, senior vice president and head of biotherapeutics R&D at Pfizer ($PFE), that means focusing more on Phase IB trials, to allow for a more patient study of how a potential drug might behave in the body. Perry Nisen, senior vice president of science and innovation at GlaxoSmithKline ($GSK), advocated combining molecules earlier in the clinical trial process.
"If you start early combining molecules because you know you have to hit a different pathway and have to hit that pathway harder, you're more likely to have success," Nisen said. Rethinking trial size in that context can also help, he added, testing as few as 10 people at a time. That then allows for creative, adaptive trial designs as you go, he said, which "is leading to more success."
Briggs Morrison, executive vice president of global medicines development for AstraZeneca ($AZN), concurred, noting, "our biggest competitor is our past success. How do you beat things like that? You are looking for big treatment effects early on. And you can do relatively small trials to rule out that big effect."
More measured research and smaller trials may help boost success rates. And the panelists agreed that collaboration with doctors, academics and others in industry is also making a difference. But the improvement is a matter of just a few percentage points overall, some noted, with a large part of their collective R&D enterprise amounting to a big gamble. But, as J&J's Fitchet argued, you still need that risk in the race to address unmet medical needs in society.
"You often don't have outcomes you need for approval," Fitchet said. "But if the area is a massive need you go forward. You balance your portfolio with risk, and you understand you are going forward with that risk."
The panelists said that while more work needs to be done to address a broader slate of development programs, regulators in the E.U. and U.S. have made strides toward accommodating new drug development/clinical trial paradigms for breakthrough therapies. Nisen said, for example, that regulators, pharmaceutical companies and academics are increasingly working together to design studies that generate useful data more efficiently. But AstraZeneca's Morrison said the FDA tends to be more adaptable right now for breakthrough therapies.
However, increased efficiency only works when drug companies understand the biology of the disease they are seeking to treat. Morrison said there have been limits, for example, in coming up with viable new drugs to treat depression.
"We haven't made much progress in understanding biology that give us druggable targets [for] experiments," Morrison said. "As you look across the industry and across medicine, there are disease areas ripe for development, and disease areas that, based on our understanding, aren't particularly right today." But, he said, subsequent research can make those disease targets viable again.