Starting with insulin over six decades ago, biologics have become the fastest-growing class of therapeutic compounds. They have provided treatment options for people who suffer from some of the most serious medical conditions, such as rheumatoid arthritis, cancer, rare blood disorders, multiple sclerosis, diabetes and HIV/AIDS. Thanks to biologics, these patients can now be treated; whereas no effective therapies were previously available. About 300 biologics are now available for human use, and account for over $200 Million in global sales in 2016. The demand is growing exponentially due to the fact that they can have fewer side effects than broadly acting drugs and can treat some indications that small molecule drugs haven’t been able to. However, about half of the biologics on the market are about to have their patents expire, which has led to the emergence of biosimilars. The global biosimilar market is expected to reach $10.90 Billion USD by 2021 from $3.39 Billion USD in 2016.
But what exactly is a biosimilar? Is it what people call “generics”? And can it truly replace a biologic?
Biologics vs. Biosimilars
Biologic drugs are large, complex proteins made from living cells through highly complex manufacturing processes. Unlike generic drugs, which are copies of chemical drugs, a biosimilar is a copy of a biologic medicine that is similar, but not identical, to the original medicine. It enters the market subsequent to a previously authorized version whose patent has expired and is approved only after showing that it is “highly similar” to an approved biological product, known as a reference product, in terms of safety, purity, and potency, and in some cases efficacy, with allowable minor differences. To be called a biosimilar, these compounds need to demonstrate structural and functional similarities with comparable pharmacokinetic and pharmacodynamic properties to the reference product.
Is it easier to get Biosimilars approved by Regulatory Agencies?
Compared to a biologic, it can be easier to get a Biosimilar approved by regulatory agencies. When the patents of biologics started to expire in the 2000s, only a few biosimilars were approved due to vague product guidelines, regulatory uncertainties and cautious physicians. However, with clearer guidelines now, the rate of biosimilar development and approval has accelerated. Regulatory agencies such as the European Medicines Association (EMA), the Food and Drug Administration (FDA), and Health Canada (HC) have developed strict regulatory guidelines for the evaluation and approval processes of biosimilars regarding their physical, chemical and clinical traits, in order to pave the way for rapid development and approval, and increase market access and affordability. The EMA, FDA and HC will only approve a biosimilar product if it has the same mechanism of action, route of administration, dosage form, and strength as the reference product.
Though manufacturers may intend to “copy” a biologic drug, a biosimilar with a different manufacturing process will never be identical to the reference product since, for many biologics, the posttranslational modifications make even the reference product a mix of compounds with slightly different structures. As a result, biosimilars go through a rigorous evaluation approval process to show that they are as safe and effective as the original biologic at treating the diseases they are indicated for. The manufacturer also has to produce evidence regarding the quality control of the processes involved in the formulation. Once the biosimilar is approved, it needs to be monitored continuously to detect adverse events which may not be detectable during the development stage.
Are Biologics and Biosimilars interchangeable?
Because the structural difference between biologics and biosimilars is so minimal, it becomes very easy to make the mistake of assuming they are identical. However, this does not make them interchangeable. Not all patients will react to a biosimilar in the same way as they do to the original biologic, and switching medications could potentially cause a change in a person’s condition. The FDA also stresses the importance of naming and labeling the products with both their original brand name and the biosimilar “generic” name, to reduce risks and ensure the patient receives the drug intended by his/her physician so that the source of any adverse events can be accurately traced.
Is cost driving choice?
Biosimilars are often given the same indications as the originator drugs in order to reduce the development cost, hence the market price, making it more accessible and affordable to patients. As more biosimilars roll out into the market, the savings patients have from the reduced costs are very large. If patients have the same treatment success with the biosimilar, why pay the higher price for the reference drug?
What does the future hold?
There’s little doubt that biosimilars will ultimately gain further traction in the coming years as multiple companies, both traditional generics players and originators, work hard to develop biosimilar versions of blockbuster biologics whose exclusive patents will expire by 2020, including Lantus, Rituxan, Herceptin, Remicade, Enbrel, Neulasta, Avastin, Aranesp and Humira. However, only a handful of these companies will have the financial resources to compete in the biosimilar market due to the high manufacturing costs, complexity of production and unclear regulatory policies involved in the development of these drugs. As the biosimilar pipeline continues to grow, it will be interesting to monitor and see if the number of emerging biosimilars will truly surpass the number of new biologics coming into the market.
Our deep expertise and capabilities in a broad range of therapeutic areas encompasses preclinical and early clinical studies for both small molecules and biologics. We can manage your entire program, as well as provide comprehensive support research services and bioanalytical expertise.