The recently published study (link is external) by Dr Joseph DiMasi and colleagues from the Tufts Center for Drug Development puts the average cost of drug development at $2.6billion. Affimer technology could offer solutions to reduce these costs and improve the efficiency of the drug development process.
This $2.6billion price tag consists of out-of-pocket costs of $1.4billion and returns that investors forego on that money during the decade and more that a drug candidate spends in development of $1.2billion. Another $312million is then spent on post-approval R&D studies- to test new indications, formulations and dosage strengths- giving a total life-cycle cost of $2.9billion per drug that reaches the market.
Although a lot of effort has been spent on improving the efficiency of the drug development process in recent years, this study shows that costs have increased 2.45 fold over the 2003 costs. The authors suggest that this is largely due to increased clinical development costs, stemming from increased clinical trial sizes and complexity. Compared to previous analyses of the drug development process this study, covering the period from the 2000s to the mid-2010s, shows higher phase III costs relative to the earlier phases. Yet these sky-rocketing prices are partially offset by the increasing trend of drug developers to ditch failing drugs earlier in the development process and shorter approval phases by the regulatory authorities.
The cost of failed R&D is built into this drug price estimate. The high cost of pharmaceutical drugs has become a controversial issue, with many arguing over how drugs should be priced; whether this is according to the developmental costs afforded by pharmaceutical companies or the value of the drug to the patient. This cost estimate shows that producing the medicines we have come to rely on is an expensive long-term process, coupled with high risks of failure.
What’s more drug categories that pharmaceutical companies are beginning to explore, such as oncology and neurology, are statistically associated with lower success rates and so higher average costs. Bristol Myers Squibb’s ipilimumab, a monoclonal antibody therapeutic for the treatment of advanced melanoma, cost $3.4billion, a 31% increase over the average. Torcetrapib (link is external), a drug being developed by Pfizer to treat hypercholesterolemia and prevent cardiovascular disease, cost $8billion before being abandoned due to trial costs.
Overall the probability of drug that enters clinical testing eventually being approved between 2000 and the mid-2010s was 11.83%. This is almost half the 21.50% clinical success rate observed in the previous study from the 1990s to the mid-2000s. While it is difficult to know definitively why the failure rates have increased a number of factors may contribute: regulators may have become more risk averse following safety failures, where drugs such as Vioxx (link is external) have reached the market; the increasing focus of industry on areas where the science is more difficult such as chronic and degenerative diseases; and that there has been substantial growth in poorly validated drug targets identified.
Increasing identified drug target validation should increase the clinical success rate of the drug development process and consequently reduce drug development costs. The use of Affimer binders and inhibitors could allow for a more detailed characterisation and validation of drug targets prior to them being incorporated into drug development programmes. Affimer reagents are highly specific binders that can be targeted to any protein. They have been used to successfully probe protein expression and location and inhibit protein-protein interactions (link is external) inside cells to examine target protein function. In this capacity Affimer proteins can function in an analogous manner to genetic technologies to probe potential drug target function and any effects resulting from inhibition.
Affimer technology has recently proven successful in the rapid production and characterisation of novel biotherapeutic candidates to inhibit the cancer immune checkpoint, PD-L1. The use of this rapid, high-throughput discovery platform could offer significant contributions to the drug development process, to increase efficiency and bring down these apparently escalating costs. Screening the Affimer library against a potential drug target can identify hundreds of possible candidate Affimer biotherapeutics. These can be rapidly characterised according to their production characteristics, binding and inhibition within a matter of weeks, using our high throughput process to allow the selection of the best candidate molecules to enter the pipeline. Affimer proteins could be used directly as biotherapeutics, acting in an inhibitory or non-inhibitory fashion for validated drug targets to improve the speed and success of the drug development process. Equally they could be used to screen potential drug candidates in a drug displacement screen, where Affimer proteins bound to their targets are screened against small molecule candidates. The displacement of Affimer binding in such as screen would indicate high affinity molecules to the specific targets, which could form a quality basis for lead compound development.