Biologic therapeutics, like antibody drugs, are predicted to be the future of drug development. How successful are they really? Will biologics soon dominate the pharmaceutical world?
Small molecule drugs
In the past, pharmaceutical development has been dominated by so called small molecules. These organic molecules with sizes ranging from about 500 to 900 Da make up a major part of the pipelines of pharma companies still. Their pharmacokinetic properties are relatively easy to optimise, their production is uncomplicated and they have a long track record of success. On the downside, they often lack specificity, which attributes to their high failure rate of >90% in clinical trials.
“Small molecule drugs are optimised for high selectivity, but seldom for specificity.”
For the last 40-45 years, the novel segment of biotechnology has advanced into the pharmaceutical sector. Biotechnology products – or biologics – cover a wide range of molecular classes. They range from proteins, like monoclonal antibodies, to peptide drugs up to vaccines as well as gene and cell therapy products.
The advantage of biologics is their high effectiveness when compared to small molecule drugs. They usually react highly specific against one target, which results in less undesirable side effects and low toxicity. A major barrier for the success of biologics, especially peptide and protein drugs, has been their lack of oral absorption. Recently, new delivery systems have been developed to overcome this disadvantage. Another hurdle to the wider adoption of biologics has been the transition of candidates from academic to industrial research and difficulties in large scale production of biotechnological products. Compared to the production of small molecules, biologics production is highly complex. For example, protein therapeutics are produced in living cells, they require several post-translational modifications to enhance their specificity and complex purification processes to ensure their safety.
“The high specificity of biologics results in less side-effects and low toxicity.”
Increasing number of approved biologics
Despite these barriers, biologics have become largely successful in the last years.
The number of new biologics on the market is growing steadily over the past years. FDA approvals of new biologics per year increased from 14 drugs in 2012 to 24 drugs in 2015 (see below). After a slight drop of only 19 new approvals in 2016, this year already 15 new biologic drugs have entered the market.
Likelihood of success in clinical studies
The strength of biologics becomes apparent when looking at the attrition rates of new drug candidates in clinical studies. Small molecule drugs have only a chance of 6.5 % to get from clinical phase I to approval. For biologics, the success rate is 11.5 % – almost twice as good. This higher success rate is mostly attributed to the better selectivity of biologics. For example, monoclonal antibody drugs are very successful due to their high epitope specificity. In contrast, small molecule drugs are often designed for high selectivity and not specificity, resulting in off-target effects in patients.
Commercial success of biotech products
Looking at their success on the market also shows the increasing importance of biologics. While the share of biotech products sales was only 8 % of all drug sales in 2002, it increased up to 18 % in 2014. In the same year, 52 biotech products were rated as blockbusters, compared to 67 small molecule blockbuster drugs.
By far, the commercially most successful biologics are monoclonal antibodies. They make up about half of all biopharmaceutical sales. In 2008, monoclonal antibody sales amounted to $39 billion and increased by 90 % to $75 billion in 2013.
“Monoclonal antibody sales increased by 90 % from 2008 to 2013.”
Controversy over the pricing of biologics
Part of the commercial success of biologics results from their success for indications in fields where few or no other drugs are available. This leads to premium pricing of several biotech products with costs of over $100 000 per year, per patient. In recent years, payers have started to push back on these high prices. In addition, the approval and production of biosimilars – the counterpart of generics in small molecule drugs – is gaining impact on the drug market.
BIO (2016), Clinical development success rates 2006-2015.
Ecker et al. (2015) The therapeutic monoclonal antibody market. Bioprocess Technology Consultant, mAbs. 7: 9-15.
M.J. Espiritu, et al. (2014) A 21st-century approach to age-old problems: the ascension of biologics in clinical therapeutics. Drug Discovery Today. 19: 1109-1113.
R.P. Evans (2015) Pharma success in product development – does Biotechnology change the paradigm in product development and attrition. The AAPS Journal. 18: 281-285.
Food and Drug Administration (accessed July 21st 2017) Purple Book: Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations.
Lagassé et al. (2017) Recent advances in (therapeutic protein) drug development. F1000Research 6(F1000 Faculty Rev):113.