Small Molecule Revival
Written by Dr Niamh O’Reilly

An increasing focus on biological therapies in recent years has meant that many pharmaceutical companies have scaled down their efforts to research and develop chemically synthesised “small molecule” drugs (1, 2). Biological therapy sales generate an increasing portion of pharmaceutical market share and arguably the most interest, yet they currently treat a limited range of diseases and can also be prohibitively expensive and inaccessible to patients if not reimbursed.

Media reports about innovation in the pharmaceutical industry are often prolific with acronyms such as CAR-T, PD-L1, PARP, CRISPR and mAb in referring to a range of cell based, biological and gene editing therapies. These therapies capture the imagination and draw attention for introducing innovative never-before-seen ways to treat serious disease. However, many of these treatments have yet to be tested by long term real world post-market use, while some can also cause serious side effects that negatively impact patient quality of life.

In 2017, the ten most prescribed and commonly used drugs in Australia were “small molecule” therapies (3). These are mostly well established drugs proven to be effective in treating common and chronic disease symptoms. However, small molecule doesn’t necessarily mean old drug (1). Indeed, there are a growing number of companies focusing on developing new, cutting edge chemically derived drugs. For example, ivacaftor is a small molecule drug tailored to treat specific subsets of people with cystic fibrosis for the first time targeting the underlying causes of the disease.

Another company has shown that an innovative approach to delivering of a small molecule drug via inhalation could set their product apart from competitors (4). This therapy is designed to block a molecule highly expressed in cells involved in scarring in the lungs of people with idiopathic pulmonary fibrosis (4). Another approach is to revamp and improve old drugs such as platinum chemotherapy which is effective but highly toxic resulting in side effects that can limit a patient’s tolerability to treatment. Clever reengineering of platinum chemotherapies could enable their targeted delivery in a way that effectively kills cancer cells thus limiting toxicity to patients (5).

Media reports often praise biological therapies or “large molecules” as providing ground breaking healthcare solutions, yet the above mentioned cases are just three examples showing that “small molecules” too can play in this space and compete with the “big guns” in the innovation stakes.

CRC’s experienced Medical Affairs team has the expertise to bring the value story of new molecules, big and small, to life via evidence generation initiatives and solid communication strategies.   



  1. Cohen, Y. Small Molecules: The Silent Majority of Pharmaceutical Pipelines. Xconomy Inc, 2015. Available at: https://bit.ly/2OJKV36
  2. Dale, A. New British Biotech Receives £3M to Develop Small Molecules that Fight Cancer. Labiotech, 2017. Available at: https://bit.ly/2OKlbUe
  3. Top 10 drugs 2016-17. Australian Prescriber, 2017. Available at: https://bit.ly/2Q6nQfP
  4. Smith, J. Danish biotech closes 79M Euro Series C to develop inhaled lung disease drug. Labiotech, 2018. Available at: https://bit.ly/2TeBqMP
  5. Toohey, M. UT’s inventor of the year, challenges odd in life work. 2017. Available at: https://atxne.ws/2DHwQCj