Timelines of translational science: From technology initiation to FDA approval

Abstract

While timelines for clinical development have been extensively studied, there is little data on the broader path from initiation of research on novel drug targets, to approval of drugs based on this research. We examined timelines of translational science for 138 drugs and biologicals approved by the FDA from 2010–2014 using an analytical model of technology maturation. Research on targets for 102 products exhibited a characteristic (S-curve) maturation pattern with exponential growth between statistically defined technology initiation and established points. The median initiation was 1974, with a median of 25 years to the established point, 28 years to first clinical trials, and 36 years to FDA approval. No products were approved before the established point, and development timelines were significantly longer when the clinical trials began before this point (11.5 vs 8.5 years, p<0.0005). Technological maturation represents the longest stage of translation, and significantly impacts the efficiency of drug development.

Patterns of Innovation in Alzheimer’s Disease Drug Development: A Strategic Assessment Based on Technological Maturity

“…Thus, drug development becomes significantly more efficient once the associated technology passes the established point. Finally, our data suggest that the time between a scientific insight, or invention that gives rise to a new area of research, to approval of products based on this technology is 36 years, 29 an interval similar to that described by others looking at the elapsed time between seminal publications and drug approvals. 30 …”

“…25,[27][28][29] From these studies, we have shown that the accumulation of knowledge regarding specific biotechnologies, drug classes, or drug targets, as measured by the cumulative number of publications in PubMed, follows a S-curve growth pattern that can be modeled with an exponentiated logistic function (Figure 1). Using a nonlinear least squares fit of this function to the cumulative publication counts, we identify an initiation point (Ti) corresponding to the point of maximum acceleration of publication activity (max d 2 N/dt 2 ), and an established point (Te) corresponding to the point of maximum slowing of publication activity (min d 2 N/dt 2 ).…”

“…More importantly, our studies show that biopharmaceutical development follows the pattern observed in other technology sectors, with few successful projects being generated by nascent or growing stage technologies, and most new products arising from established-stage technologies. 25,28,29 Well-known examples of this phenomenon include monoclonal antibodies, gene therapies, and nucleotide therapies, in which there were hundreds of clinical failures during the 420 years before the first successful products were approved. Analytical studies show that these approvals occurred only after these technologies passed the established point.…”

“…All 6 of these NMEs entered clinical development before the point at which amyloid-related technologies would be considered established. In contrast, for all targeted and biological products approved from 2010 to 2013, the clinical entry point averaged 5 years after the established point, 29 and the 3 AChE inhibitors on the market entered clinical development 17 years after AChE technologies passed this point.…”

Genetische Risiken und Therapieentwicklung bei Netzhautdegenerationen

“…Man muss jedoch bedenken, dass neue Erkenntnisse aus genetischen Studien für komplexe Netzhautdegenerationen zum Teil erst seit Kurzem bekannt sind, was deren therapeutische Umsetzung erst in der nähe-ren Zukunft erwarten lässt. So braucht es durchschnittlich mehr als 40 Jahre von der ersten Beschreibung eines Prozesses bis zur Markteinführung eines darauf aufbauenden Medikaments [36]. Auch könnte das Wissen um genetische Risikovarianten nur einen begrenzten Einfluss auf einen Therapieerfolg haben [37], zumal eine Risikovorhersage von komplexen Erkrankungen naturgemäß fehlerbehaftet ist [29,38].…”