frameworks, and clinical care and monitoring. All these variables impact how much effort and money is spent on R&D by pharmaceutical companies, which is similar to the issues noted earlier in this chapter with regards to antibiotic R&D. There is an unmet need for treatment of orphan diseases as well as for more effective cancer treatments. Regulatory agencies around the world have taken steps to address development and patient access to rare disease medicines. National plans can encompass funding for orphan disease drug access, research incentives, diagnosis programs, care coordination, and early access programs.33
Access to life‐saving medications brings immeasurable benefit to patients; however, it comes at a significant cost for payers. Across the world, some of the recently approved biologic drugs, including gene therapies, have placed immense strains on payment systems and put into question their long‐term sustainability especially considering the pharmaceutical pipeline that lays ahead. Public and private organizations around the world are working with pharmaceutical companies, insurers, governments, and patient advocacy groups in attempts to better align financial expenditures with clinical benefit. Several organizations perform health technology assessments (HTA) that evaluate new drugs in a systematic fashion to assess clinical safety and efficacy as well as cost‐effectiveness. It is expected that independent review of drug pricing by groups like the Institute for Clinical and Economic Review (ICER) may be able to place downward pressure on drug go‐to‐market prices in the coming years. Outcomes‐based contracts that tie reimbursement for a given pharmaceutical to meeting certain clinical metrics are also expected to become more prevalent. It is predicted that by 2022, 30 out of the 50 top drugs will have some form of outcomes‐based contracts in place between pharmaceutical manufacturers and payers.32
Biosimilars, which are similar versions of innovator biologic drugs, are expected to generate cost‐savings compared to the innovator/reference brand that they compete with. The adoption of biosimilars in the United States has been relatively slow compared to other developed markets like the European Union. It is expected that the adoption of biosimilars in Europe will continue to outpace the United States for the upcoming decade; however, major events are on the horizon in the United States including the introduction of the first biosimilars to Humira®, currently the world's top‐selling drug.32 A concerted effort by countries and payers across the globe to educate prescribers and patients on the safety and efficacy of biosimilars will be required to see similar type of savings that small molecule generics generate today.
3.6 Summary
Considering the complexities associated with developing, manufacturing, administering, and paying for biologic drugs, a fundamental question is why the science of drug discovery is moving away from small molecule drugs to biologics? In short, because there is no better alternative that is currently available. In the ongoing development of safer and more efficacious drugs, biologics are the logical next step and this will continue to be the case in the foreseeable future. Most human diseases are caused by signaling imbalances, which involve numerous protein–protein interactions. Biologics afford the capability to alter such complex signaling systems in ways that small molecule drugs, to date, have not been able to. It is estimated that of ~20 000 human proteins, only about 3000 can be regulated by small molecule drugs.34
The treatment spectrum of biologic therapeutics is broad. They can limit pro‐inflammatory cytokines that erode synovial tissue in rheumatoid arthritis, stimulate red blood cell production in kidney disease, replace the deficient insulin in diabetes, or influence the body to attack cancer using the natural immune system. The umbrella term, biologics, includes the gene therapies used to treat and/or cure diseases that have had little to no treatment options currently. R&D of gene therapies will continue in the upcoming decade and will provide the opportunity for potentially curing certain diseases.
It will be incumbent upon pharmaceutical manufacturers and payers to strike a balance that ensures continued innovation is affordable and accessible on a global scale. Rare diseases that result in dismal health outcomes require therapies that do not exist today and, in many cases, treatment options that exist for diseases today can also be dramatically improved. Precision medicine, including the improved identification of biomarkers and a better understanding of pharmacogenomics, will be one pathway toward finding the nexus of cost‐effectiveness and value. While biologics will not cure all diseases or solve all health problems, they will be an integral part of drug therapy in the foreseeable future.
References
1 1 Sonnedecker, G. (1993). The founding period of the U. S. pharmacopeia: I. European antecedents. Pharmacy in History 35 (4): 151–162. www.jstor.org/stable/41112530 (accessed 24 September 2019).
2 2 Ng, R. (2015). Drugs: From Discovery to Approval. Hoboken, NJ: Wiley.
3 3 Jones, A. (2011). Early drug discovery and the rise of pharmaceutical chemistry. Drug Testing and Analysis 3: 337–344. https://doi.org/10.1002/dta.301.
4 4 Timeline of drug development (2018). Page last edited on 15 June 2018. https://timelines.issarice.com/wiki/Timeline_of_drug_development (accessed 3 August 2019).
5 5 Kirsch, D. and Ogas, O. (2017). The Drug Hunters: The Improbable Quest to Discover New Medicines. New York, NY: Arcade Publishing.
6 6 Liu, Angus (2018). From old behemoth Lipitor® to new king Humira®: best‐selling U.S. drugs over 25 years (14 May) [Online]. FiercePharma. https://www.fiercepharma.com/pharma/from‐old‐behemoth‐lipitor‐to‐new‐king‐humira‐u‐s‐best‐selling‐drugs‐over‐25‐years (accessed 24 September 2019).
7 7 Mellstedt, H. (2013). Clinical considerations for biosimilar antibodies. EJC Supplements: EJC: Official Journal of EORTC, European Organization for Research and Treatment of Cancer … [et al.] 11 (3): 1–11. https://doi.org/10.1016/S1359‐6349(13)70001‐6, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048039 (accessed 24 September 2019).
8 8 The United States Food and Drug Administration. What are “biologics” questions and answers. https://www.fda.gov/about‐fda/about‐center‐biologics‐evaluation‐and‐research‐cber/what‐are‐biologics‐questions‐and‐answers (accessed 24 September 2019).
9 9 Lybecker, K. (2016). The Biologics Revolution in the Production of Drugs. Fraser Institute https://www.fraserinstitute.org/sites/default/files/biologics‐revolution‐in‐the‐production‐of‐drugs.pdf (accessed 24 September 2019).
10 10 United States Food and Drug Administration (2015). Frequently asked questions about therapeutic biological products (7 July). https://www.fda.gov/drugs/therapeutic‐biologics‐applications‐bla/frequently‐asked‐questions‐about‐therapeutic‐biological‐products (accessed 24 September 2019).
11 11 Gurevich, E.V. and Gurevich, V.V. (2014). Therapeutic
