Dr Georgia Demetriou explains what biosimilar drugs are, and how they will be able to drive down the cost of HER2 therapy, improving patient access by improving affordability and ultimately patient outcomes.
Many of the ‘newer’ therapies being used in the treatment of breast cancer are agents termed biologics. Biological therapy involves the use of living organisms; substances derived from living organisms; or laboratory-produced versions of such substances to treat disease.
They are often 200 to 1 000 times the size of a small molecule or chemical drug, and are far more complex. They are highly sensitive to temperature and pH, making them more difficult to characterise and produce on a large scale. Even small changes in growth conditions can result in changes in cell behaviour, and differences in the structure, stability and other quality aspects of the end product. Any of these differences have the potential to affect the treatment’s safety, efficacy and shelf life, and increase the risk of an unwanted immune response.
Monoclonal antibodies (Mabs) are laboratory-produced antibodies that bind to specific antigens expressed on the surface of cancer cells. Yet, they are either absent or low in concentration on the surface of normal cells.
Trastuzumab (Herceptin) targets the human epidermal growth factor receptor 2 (HER2), binding to the cell surface growth factor receptors and stopping the receptor from signaling in a normal manner. This change in the normal signaling pathway results in a disruption of normal growth and an induction of cell death.
Unlike generic medicines, in which the active ingredients are identical to the reference small molecule drug, biosimilar medicines will not be identical to the reference biologics. This is due to processes associated with translating biologics from living cells in the laboratory to mass-production molecules.
A biosimilar drug can only be highly similar to the reference product it is designed to resemble as there is no way to make identical copies of biologics.
The objective of biosimilar drugs is to provide a process of simplification, designed to reduce production costs and encourage competition.
The approval process for biosimilar medicines to come to market requires that there be no clinically meaningful differences between the biosimilar product and reference product in terms of safety, efficacy, purity, and potency.
The demonstration of biosimilarity needs to be demonstrated in a clinical trial. The concept of interchangeability exists when we discuss biosimilar drugs. This is a higher requirement where there is the expectation of the same clinical results in any given patient, for a product that is administered more than once. With no additional risk to safety or diminished efficacy when switching or alternating the biosimilar and the originator.
There are currently six biosimilar drugs for trastuzumab that have been developed and have been studied in clinical trials. The results of one of these trials were reported and was approved by the US Food and Drug Administration (FDA) in July 2017.
At the Wits Clinical Trial Unit, administered through the Wits Health Consortium, I have been fortunate to be involved in the potential registration trials of three of these agents.
By offering patients the opportunity to participate in these clinical trials, many patients, especially, those in the state sector, who to date have not been able to access trastuzumab, were able to receive either the reference product Herceptin or the biosimilar.
The avalanche of biosimilar medicines for trastuzumab can only be good news for patients with HER2-positive breast cancer. These drugs will be able to drive down the cost of HER2 therapy, bettering patient access by improving affordability and ultimately patient outcomes.
MEET OUR EXPERT – Dr Georgia Demetriou
Dr Georgia Demetriou is a medical oncologist at the Wits Oncology Donald Gordon Medical Centre. She is passionate about new developments and research in medical oncology and believes strongly in multi-disciplinary care. Her areas of special interest include endocrine, gastrointestinal and breast tumours. She has been involved as an investigator in a number of clinical trials.