Alzheimer’s remains Holy Grail for drug development
If we learn from our failures, then Alzheimer’s disease presents the most exciting therapeutic area for drug discovery as it is a field littered with some of the most spectacular late stage wrecks in pharmacological research.
A complex disease, Alzheimer’s offers a range of targets that is surpassed only by the number of companies, universities, research institutes and governments dedicated to finding either a cure or a treatment of the devastating symptoms.
It is the tremendous social cost of this disease that explains why failure, even if it is an accepted option, has not discouraged the dedication to finding what has become medicine’s Holy Grail.
Ginger Johnson of Defined Health led a panel discussion entitled “Alzheimer’s Disease: Moving Forward, or Spinning our Wheels?” that was part of a new Defined Health Therapeutic Insight at BIO-Europe Spring® 2010.
The nearly religious pursuit of companies seeking rewards from this still elusive market, she explained, is supported by a schism that divides research into the so-called ‘BAptists (beta amyloid theory) and on the other side the devoted ‘TAUists,’ who seek to explain the role of tau proteins in the formation of neurofibrially tangles that contribute to the disease.
Where the BAptists were once ascendant, advancement in the understanding of Alzheimer’s basic biology has cast doubt on those theories and companies are spreading their bets onto other mechanisms like tau proteins.
Concluding her introductory remarks in a crowded conference room, Dr Johnson suggested the risk of Alzheimer’s discovery may be too big for even the biggest of the big pharma to face alone, as indicated by an alliance of Elan, Wyeth/Pfizer and Johnson & Johnson backing a bid for bapineuzumab, one of the most advanced, yet most controversial disease modifying therapies.
This collaborative effort does not address a major opportunity—and concern—for treating the disease at an early stage before the damage to the brain has been done. To date there is no clinically accepted surrogate marker, imaging technique, or cognitive testing for identifying patients, let alone correlation with a clinical response.
Andrea Cavalli leads a newly formed drug discovery and development effort dedicated to Alzheimer’s at the Italian Institute of Technology, and explained his group is pursuing an innovative multitarget research paradigm worthy of the challenge posed by this multifactorial disease.
Using two methods, the group is currently exploring where a common chemical core that binds to two targets intersects with a computed model of a chemical space related to screening candidates.
The global director for central nervous system partnering at Roche, Sarah Holland, described the kinds of proposals she is seeking for a discovery program.
“Scientific rigor,” to start she stated flatly, and after that, “a drug like molecule with the right kind of characteristics so that it gets into the brain, a well defined, well accepted, well understood animal model, dose dependent efficacy. The basic, fairly expected qualities you would expect. Yet you would be surprised how often people come forward not having these elements.”
“If you have imaging data to support a biomarker validation, that is fantastic,” she added, saying Roche would prefer biomarkers available more readily in accessible bodily fluids, a reference to earlier efforts to extract such a marker from spinal fluids.
Dr. Peter Seubert, Vice President of Research, Elan Pharma International, is a veteran of Alzheimer’s research, having been closely associated with both the highest hopes and some of the lowest points of discovery programs, most significantly with what he called the “broken AN-1792 study.”
The perspective offered by his peregrinations provided a rich background for not only the evolution of developments in Alzheimer’s research but a cautionary tale as well for future programs.
The investor’s perspective was offered by Manuel Lopez-Figueroa with Bay City Capital who quickly defined the boundaries noting that discovery and development programs for Alzheimer’s are an expensive endeavor with no hope of an initial public offering as an exit from such an investment.
“So we engage as closely as possible with pharma to understand the milestones that need to be achieved and at what clinical level. The answers will be slightly different depending upon who we are speaking with, where one may not find Phase I clinicals to be compelling and another asking whether there is a platform that is applicable to other targets or indications.”
Noting that new investment models have emerged, he said “participation by corporate capital funds is especially reassuring as the milestones are often defined by the very companies that are potential buyers of the developed drug.”
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