Big Pharma R&D Chiefs On IRA’s Unintended Casualty, Product Life Cycle Compression

Big pharma R&D heads deliberated the wider neurodegenerative disease landscape and where things stood on the spectrum.

Amgen’s executive vice president, R&D, David Reese noted that industry was now getting proof of principle on clinical trials methodologies, on endpoints and “what actually constitutes a positive result”. While that may be a very basic question, it’s been one that had been unanswered for many years in the field.

Refining those methodologies, and in particular, developing surrogate markers of effect needs to be one of the clear objectives in the field because “we want don't want to go another 20 years or another turn of the wheel as we attempt to do things empirically and we can't do it trial-by-trial because it simply takes too long, ” he explained.

‘Understanding intermediates and surrogate predictors of efficacy and safety is an area where the field needs to shine a bright light right now,” Reese added.

Lilly’s executive vice president and chief scientific and medical officer, Daniel Skovronsky, kept the tenor upbeat, suggesting that Lilly was not done yet; the next step is to “go even earlier” and the company was doing prevention studies, which probably holds even greater promise for amyloid modulator drugs, while also working on tau targeted drugs for Alzheimer's disease, he indicated.

“Alzheimer's is one of many neurodegenerative diseases, and maybe progress on Alzheimer's empowers us to think more boldly about other neurodegenerative diseases and maybe we can have similar progress on some of these others. The technologies are there today -we're starting to see progress on dreaded things like ALS [amyotrophic lateral sclerosis], more to come on Parkinson's, and frontotemporal dementia,” he added.

Fiona Marshall, President, Novartis Institutes for BioMedical Research, noted the over the last 10 years there has been a much better fundamental understanding of some of the neurodegenerative diseases from a mechanistic point of view, greatly informed by human genetics.

But the challenge has been that “we know what the targets are, but how do we actually drug these pathways?” the former MSD executive said, also referring to the difficulty with getting molecules into the brain, particularly large molecules. Marshall was previously senior vice president and global head of discovery sciences, preclinical development and translational medicine at MSD, as Merck & Co is known outside Canada and the US.

“I'm hopeful that advances in better delivery, for example, into the CNS will allow us to bring other modalities on the same targets. From our point of view, we're concentrating a lot on oligonucleotide therapies and siRNA delivery mechanisms into the CNS,” Marshall said