Small molecule drugs make up 90% of global drug sales in today’s pharmaceutical market. In the past decade, newly emerging classes of drugs, including biologics and biosimilars, are increasingly gaining traction. Biologics and biosimilars have been shown to have promising efficacy when used to treat cancer and autoimmune diseases, with high specificity. However, information about these different drug classes can be difficult for the public to grasp, and there are multiple differences between small molecule and biologic drugs, their manufacturing processes, and their limitations.
Small Molecule Drugs
Small molecule drugs are compounds manufactured through chemical synthesis; thus, they generally have well-defined chemical structures. This class of drugs includes most patented medicines on the market and their generic counterparts.
Patented medicines are trademark-protected drugs. A patent provides exclusive rights to the patent holder and allows the manufacturer to produce the brand-named product exclusively on the market. While generic drugs have the exact same chemical structure as its patented counterpart, it can only be sold on the market after the patent on the drug expires.
Current Canadian law provides 20 years of patent protection from the filing date of the patent application. However, the actual length of market exclusivity is usually much shorter (7-9 years) due to the extensive research and proof of safety that takes place before the drug is released to the market. Companies spend $1.2 billion/year on research and development for patent medicine. The large investment in the development of patent medicine often leads to the high cost of these drugs on the market.
Generic drugs are a great alternative since they are compositionally the same as brand name drugs but come with a price reduction of up to 25%. This price difference is possible since generic drugs do not require extensive testing and large financial and time investment compared to their brand name counterparts.
Biologic Drugs
The first biologic drug, a biosynthetic “human” insulin made from recombinant DNA, was marketed in 1982 by Genentech. A biologic drug is a substance that is extracted from, semi-synthesized by, or manufactured in living organisms. Whereas most generic drugs are chemically synthesized small molecules, biologic drugs are much more complex in their composition. Some biologic drugs include antibodies, interleukins, and various vaccines. Recently, biologic drugs have been making the news as an alternative treatment method for autoimmune diseases and cancers. The development of biologic drugs has revolutionized cancer treatment for patients since these complex drugs can interact more specifically with the host immune system, leading to more targeted treatment. An example of biologic drugs includes immune checkpoint inhibitors for cancer treatment.
With the development of biologic drugs comes biosimilars. As the name suggests, a biosimilar is a biologic drug that is highly similar but does not need to be identical to its reference biologic drug. Biosimilars can cost 25-50% less than their reference counterparts since they are not patented. Since the production of biosimilars can be highly variable, Health Canada requires pharmaceutical companies to prove similarity in function between biosimilars and their reference drugs. Furthermore, clinical tests for the safety and efficiency of biosimilars are also required.
For a biosimilar to be on the market, it must overcome many hurdles. Even if biosimilars are allowed for marketing in Canada, Health Canada may deny authorization for a biosimilar to be used as a treatment for certain diseases, for which the reference biologic drug can be used, based on scientific and benefit/risk-based evaluations.
Since biologic drugs are produced from living organisms and are more structurally complex than chemical drugs, slight changes during the manufacturing process may lead to unwanted side effects. Despite the strict testing process for biologic drugs and biosimilars, many people still have concerns about the safety of biosimilars. The differences in extraction source, processing protocols, and isolation methods between biosimilars and their reference biologic drugs can affect the safety and effectiveness of the product in patients. Examples of inherent variabilities of biologic drugs includes glycosylation, phosphorylation, deamination, methylation, and acetylation. A single monoclonal antibody can have millions of molecular variants based on post-translational modifications.
Another problem in using biologic drugs and biosimilars is that they may be immunogenic. This can occur when the patient’s immune system recognizes the drug as a foreign substance, leading to the production of antibodies against it. Oftentimes, for many biologic drugs, it is unpredictable whether a patient will develop an immunogenic response to the treatment. The antibody produced against the biologic protein may exacerbate disease symptoms since the produced antibody may also recognize host proteins, to which the drug may share structural similarities.
While biologics and biosimilars provide more effective treatment for patients with cancer and autoimmune diseases, their safety and low responsive rate can still be improved. This will require the government of Canada to adopt better regulatory and more thorough examination processes. Manufacturers producing biologic drugs and biosimilars need to test for drug safety and efficiency after every change made to their manufacturing protocols.
The regulation of these two class of drugs are also different. The regulation for small molecule drug is more mature while there is still room for improvement for the regulation and testing of biologic drugs in Canada. For example, determining which patient population will respond to a biologic drug can be difficult since not all patients will react to the same drug in the same way. However, the discovery of biomarkers is a great indicator for the use of biologic drugs and biosimilars since this will allow for the prediction of responsive rates in individuals. Biomarkers will allow more specific and targeted treatment for individual patients while saving valuable time for patients to get the treatment that they need. Thus, there is great future in biologic drugs and biosimilars to treat complex diseases; with proper regulation, patients suffering from cancer and autoimmune diseases can greatly benefit from them.
Helen Wang
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Ms.Wong,
very informative and well researched. thanks!