According to a Markets and Markets report, a new class of drugs—biosimilars—is expected to reach a global market value of $10.90 billion by 2021. The Research and Development (R&D) of such drugs is growing exponentially, with South Korea also emerging as one of the key manufacturers in the biosimilar market. Celltrion’s Truxima— a biosimilar of Mabthera, one of the world’s top selling cancer drugs—was recently launched in the European Union. In addition, Samsung’s Bioepis recently gained approval from the Food and Drug Administration (FDA) for Renflexis, a biosimilar of Johnson and Johnson’s (J&J) top selling Remicade. At the forefront of this industry, these companies are expected to go head to head with some of the largest figures in healthcare.
Put simply, a biosimilar (or a followon biologic) is a biopharmaceutical drug that functions based on the patent expiration of a reference biologic drug from a different manufacturer already in commercial use. The R&D of biosimilars is gaining momentum as numerous patent expiries, including more than 10 blockbuster drugs (biologics generating revenue higher than $1 billion) that are in motion.
Biopharmaceuticals derive from living cells or organisms such as bacteria or protein, and are prescribed through infusion. In contrast to the small-molecule drugs most people are familiar with those that are ingested and manufactured through an entirely chemical process, these pharmaceuticals are manufactured using biotechnology; a prime example being the hormone insulin.
Biologics have been pivotal in the treatment of a variety of chronic or severe medical conditions that range from HIV, diabetes, to cancer and rare blood diseases. However, they still remain some of the costliest treatments for patients. The biosimilar industry stands to provide a more affordable alternative and is gaining market attention as a result, and paving the way for biosimilar development.
Development and Approval Process of Biosimilar Drugs
Professor Kim Yong-hee, Head of Hanyang University (HYU)’s Biopharmaceutical Research Lab, explains that advancements in genetic and molecular engineering have enabled biopharmaceuticals to selectively and precisely combat target cells, thus drastically reducing side effects and heightening efficacy.
To create a biosimilar, similarity (bioequivalence) to the original biologic is a vital factor, remarks the professor. The first step of creating a biosimilar drug is to acquire the Critical Quality Attributes (CQA)—an assessment of the reference product’s active ingredient, chemical and biological properties, manufacturing process, and more.
The very nature of biosimilars makes it so that the exact replication of its originator is impossible. As the drug and its originator biologic are produced by different manufacturers and patents only disclose so much information, the two drugs can never be identical. This inherent variability does not result in any significant clinical differences. However it does differentiate it from generic drugs—exact copies of the brand name small-molecule drugs—confirms Professor Kim.
Because biopharmaceuticals consist of complex molecular structures, as opposed to their chemically synthesized counterpart, changes may occur in the cell’s growth stage. However, the final product, to be approved by regulatory authorities, produces the same effects in any given patient.
Once the CQA is determined, a cell line is generated and tens of thousands of host cells are transfected with the DNA, screened, and evaluated for stable expression. Thus, begins the actual manufacturing process of optimizing cell culture (growth) conditions and conducting myriads of purification experiments to refine and perfect what becomes the final product.
What proceeds next is the approval of the drug which is overseen by various authoritative bodies differing by market. “Conventionally, to determine similarity, non-clinical studies (analytical) and clinical studies both take place, the latter one mainly a pharmacokinetic (PK) study which ascertains the mechanisms of absorption and distribution,ˮ explains Professor Kim.
Technicalities and Industrial Challenges the Biosimilar Industry may Face
Innovative though biosimilars may be, the distribution of the drug is not as simple as generic drugs. Both the market and varying regulatory authorities strictly differentiate the terms due to high complexity in the underlying science and the rigorous course of approval that is needed.
What follows is a slow transition into commercialization, as the background on biosimilar drugs is not as well established among healthcare professionals. This invokes some hesitancy in physicians who consult with patients and prescribe medication. In India, for example, safety became a concern when some batches of Razumab, prescribed for macular degeneration (a disease causing loss of vision), were reported as causing inflammation.
The price cut also has yet to be influential enough to convince physicians and patients. Professor Kim mentions the competition between pharmaceutical companies and regulatory hurdles that present another barrier. A recent lawsuit involving Sandoz’s biosimilar of Amgen’s biologic, called into question whether biosimilar manufacturers should adhere to a ‘notice of commercial marketing’ provision that prolongs market entry. A precedent for how quickly patients will have access to biosimilar drugs may be set, once the US Supreme Court reaches a decision in July.
Measures in Place to Deal with Obstacles the Biosimilar Industry may Face
Despite a few challenges, Professor Kim rules it down to a matter of time, and maintains that commercialization is inevitable. Since the patents on blockbuster drugs have only recently expired, biosimilars are coming to a stage of gradual acceptance.
Discourse among healthcare professionals is still not in consensus. Like all other medicines, biosimilars are no exception to the post monitoring system in place that traces any adverse reactions to the manufacturer. So far, the European Medicines Agency (EMA), boasting the highest approval of biosimilars, has not reported any safety concerns over the last 10 years.
For competitive prices, manufacturers constantly strive to outperform each other and deliver the most affordable and effective drugs. Renflexis, for instance, is the second biosimilar of J&J’s Remicade and is forcing the pharmaceutical giant to cut down on its hefty prices in order to maintain the market share of one of its bestselling drugs. The ultimate take-away from this growing market is that it could end up saving the healthcare industry an inordinate amount of money in the long run.
Future Outlook and Development Potential for Biosimilars
As the R&D of biosimilar gains momentum, potential for the industry is only broadening with many firsts being achieved. HYU’s Biopharmaceutical Research Lab, which develops drug delivery systems, patented the world’s first Adipocyte (fat cell) targeting fusionoligopeptide gene carrier, garnering a world of possibility for the treatment of obesity. “As for South Korea, biosimilars could be the next driving engine, post the I.T. industry,ˮ predicts Professor Kim.