In September 2017, the US Food and Drug Administration (FDA) approved bevacizumab-awwb for the treatment of NSCLC, with the same indications as the tradename. Although bevacizumab-awwb is the only biosimilar agent specific to lung cancer, there are many in development, necessitating a firm understanding of the regulatory approval process and cost comparators for these agents. Biosimilar expert, Gary Lyman, MD, sat down with ILCN to address the most common obstacles to the adoption of biosimilars as well as clinician and patient perceptions. Part 1 addressed biosimilar terminology, safety, and lessons learned.
ILCN: What are some of the main obstacles to the adoption of biosimilars over originators? Is cost a factor here yet, or are these agents too new to know?
Dr. Lyman: The U.S. FDA approved the first biosimilar in the United States using an abbreviation of the manufacturer’s name, SNDZ, and the nonproprietary agent name: Filgrastim- SNDZ (for granulocyte colony-stimulating factor and [Sandoz]). More recently, the agency moved away from this naming convention, because it did not want to seem promotional with approvals or enable therapeutic selection by manufacturer. Now biosimilar agents are named using the non-proprietary term and a random sequence of four letters. Although impartial and noncommercial, the downside to this convention is that it is hard to remember the names of these agents. For example, in breast cancer, which was the first cancer type for which a biosimilar agent was approved in the United States, there are five trastuzumab biosimilars with a whole array of random four letters at the end of the name. Importantly, however, if a red flag arises in the treated individuals in the form of adverse event reports, the agency is able to identify the exact agent and, if there is a consistent pattern of reports, to further explore the potential causes. While there is some ‘method to this madness’, it does result in some confusion.
In my opinion, an important obstacle to biosimilar adoption is that we, as care providers, do not like being told which of these agents to use either by the payer, our pharmacy, or the health system. I understand that concern. We have the option of still requesting the originator, but this often requires an appeal with much paperwork, which, in a busy clinic, is very challenging. However, if you feel strongly that the originator has proven safe and effective for your patients with highly curable cancers, this might be a reasonable consideration. For most clinical practices, however, it is typical for the clinician to be unaware as to which version of a biologic the patient is receiving—either the originator or a biosimilar. Of course, the motivation for payers and health systems to steer the selection of an agent is to bring competition to the marketplace and to reduce costs. It has reduced pricing somewhat in Europe. Early US data regarding filgrastim suggest that the price of the biosimilar was 10% less than that of the originator. However, for most biosimilars, we do not yet have meaningful data in the United States. In addition to time, there will likely need to be multiple biosimilars in a class before we can expect to see meaningful competition and reductions in price. Because there are now five approved biosimilar agents in breast cancer, all of which are competitors to the originator trastuzumab, this may be where we will first see available data on the impact on pricing. Biosimilars are never going to show the same price impact as generics, which can be 70% to 80% less than tradenames, but even a 10% to 20% reduction in price for a multibillion-dollar industry could result in substantial savings to the healthcare system overall.
It is important to note that pricing of originators—biologic agents—has continued to increase across the board over time. The pricing of a biologic therapy at the time of approval is just a starting point; most prices increase steadily for 15 to 20 years while under patent protection. Many biologic cancer therapies, cost well over $10,000 a month, which far exceeds the average household income in the United States. This is an unsustainable burden on the patients and on the health care system. Cost of care is a huge issue, and we really do need competition. It will be important to make sure patients across all socioeconomic segments of society have access to these therapies without the enormous financial burden or ‘toxicity’ we have seen across cancer care. Development of biosimilar agents is one way to move in that direction, but we have to do it safely and conscientiously.
The flip side for industry is that if we required the same level of regulatory approval for the biosimilars as we require for originators, the cost of developing biosimilars would likely be substantially higher than that of the originator because the cost of drug development today is far more than it was 20 years ago. So one of the reasons the FDA developed the approval framework that it did for biosimilars was to eliminate the most costly aspects of drug development that were not absolutely necessary to ensure safety and efficacy. Much of the cost of new drug development stems from multiple large phase III trials that cost tens and sometimes hundreds of millions of dollars to conduct over several years. If that same process is required of every new biosimilar, it will totally defeat the goal of getting these agents to market, reducing prices and improving access for all patients. I will just add that I think the agency did a rational and rigorous job in regulating the development and approval of biosimilars in order to reasonably ensure the safety and efficacy of these agents.
ILCN: Do patients have any awareness of biosimilars yet? If so, what are the common patient perceptions?
Dr. Lyman: Most patients, for better or worse, trust their physicians to do their homework and to administer the safest and most effective therapy on the market. Appropriately, most patients are far more concerned about the symptoms of the disease or the side effects of treatment rather than the specifics of drug development and the approval process. However, it is very important that patients become aware of biologic agents and their potential role in therapy. Some cancer societies and patient advocacy groups are starting to include information on biosimilars in patient-facing information. The Biosimilars Forum is a fairly new nonprofit, established to disseminate sustained and unbiased information about these agents to a multispecialty audience of care providers. For example, it is very important for pharmacists and nurses to be aware of biosimilar options because patients often have conversations with them about side effects and interactions.
We do need to make every effort to be transparent with patients and providers about biosimilars and ensure our patients and their caregivers that these new agents are safe, efficacious, and beneficial to the marketplace.