In pharmaceutical research, there is a gap that promising therapeutic candidates often fall into on the path from biological discovery to clinical trials. When the necessary resources and expertise are lacking, the gap can seem overwhelming.1 Enter our Translational Medicine group.
This global team of physician-scientists and researchers specializes in integrating findings from early drug discovery projects with their own deep knowledge of disease pathways and unmet medical needs. They offer insights on where a novel therapy might have the highest impact on diseases and what research needs to be done prior to clinical testing.
“It really helps to have teams thinking about clinical opportunities along with the research right from the beginning of a project,” says Evan Beckman, Global Head of Translational Medicine at the Novartis Institutes for BioMedical Research. “It streamlines and gives focus to the program and provides clarity on what the team needs to produce.”
To maximize our impact on projects, the group has adopted an open and flexible approach. Rather than committing a candidate to one disease area early on, they carry out studies in multiple small, focused patient populations. They then follow the science to identify patient groups who show the most promising therapeutic response. Often this leads to the exploration of rare diseases that are genetically well defined and have few effective treatment options.
We’re not wedded to, nor are we held down by, our disease focus areas, so we can really concentrate on capturing emerging science and driving it towards addressing unmet needs.
Evan Beckman, Global Head of Translational Medicine, Novartis Institutes for BioMedical Research
The small-scale studies also help streamline larger future efforts in more common diseases. They may, for example, provide critical safety and dosing information or establish biomarkers that allow us to easily detect a therapeutic response. Deeply understanding how a drug works in one disease, may allow us to predict success in other conditions. For example, fully understanding the inflammation pathways in patients with Juvenile Idiopathic Arthritis that were controlled by canakinumab, an IL-1b inhibitor, helped identify, and support, the approval in patients with Adult Onset Still’s Disease.
“We’re not wedded to, nor are we held down by, our disease focus areas, so we can really concentrate on capturing emerging science and driving it towards addressing unmet needs,” explains Beckman. “This helps us move quickly in new directions and nimbly across disease areas.”
At times, this approach dictates that clinical trials are trials in diseases without an existing roadmap. For example, designing a clinical trial in sarcopenia—the age-related loss of skeletal muscle mass and strength—was nearly impossible less than a decade ago, based on a lack of consensus on disease characteristics.
“There had been no accepted definition of the patient population,” says Beckman. “But the Translational Medicine leadership worked with academics and members of industry to push health ities and expert communities to come up with some accepted definitions. These now exist for the first time in Europe.2” In the U.S. these efforts have led to the approval of a statistical classification code for sarcopenia as well, advancing research of the disease at Novartis and other organizations.3,4
Butler, D. Translational research: crossing the valley of death. Nature. 2008 Jun 12;453(7197):840-2. doi: 10.1038/453840a.
Cruz-Jentoft, A.J. et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010 Jul;39(4):412-23. doi: 10.1093/ageing/afq034.
Fielding, R.A. et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 2011 May;12(4):249-56. doi: 10.1016/j.jamda.2011.01.003.
Power of Rare Diseases: Found in Translation Fishman, M.C. Science Translational Medicine. 5 (201) (pp 201-11), 2013. Date of Publication 04 Sep 2013 DOI: 10.1126/scitranslmed.3006800
A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failure. Ponikowski P., Mitrovic V., Ruda M., Fernandez A., Voors A.A., Vishnevsky A., Cotter G., Milo O., Laessing U., Zhang Y., Dahlke M., Zymlinski R., Metra M. European Heart Journal. 35 (7) (pp 431-441), 2014. Date of Publication: February 2014.
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mTOR inhibition improves immune function in the elderly. Mannick J.B., Del Giudice G., Lattanzi M., Valiante N.M., Praestgaard J., Huang B., Lonetto M.A., Maecker H.T., Kovarik J., Carson S., Glass D.J., Klickstein L.B. Science Translational Medicine. 6 (268) (pp 268ra179), 2014. Date of Publication: 24 Dec 2014.
Large-scale prediction and testing of drug activity on side-effect targets. Lounkine E, Keiser MJ, Whitebread S, Mikhailov D, Hamon J, Jenkins JL, Lavan P, Weber E, Doak AK, Côté S, Shoichet BK, Urban L. Nature. 486 (7403) (pp 361-367), 2012. Date of Publication 21 Jun 2012