“My eczema used to be so bad and nothing helped,” my 12-year-old patient told me. “It was so hard; he would cry and bite the rash to try and stop the itch,” his mom chimed in. She grabbed her phone and showed me pictures of a severe red rash covering his hands and forearms. Scratch marks covered the rash and the surrounding skin was darkened and inflamed. “But now look!” my patient said while raising his hands to show off the smooth, healthy skin on his arm. After years of failed medications, he’d finally started a new type of therapy called dupilumab, part of a class of medications called “biologics.” In one year, my patient had gone from runaway severe eczema to a barely perceptible rash. To me, it was an example of how medicine is advancing; to him, it was nothing short of a miracle. Hearing my patient’s response to his medication got me thinking about the new biologics-centric world we live in; below, I discuss the promise, perils, and future of these medicines.
The Promise of Biologics
Biologics, so called because they are molecules manufactured from a living system that works on a cellular level to modify disease, are medications that allow for a dazzling range of possibilities. Their advent has birthed an entirely new approach to therapy in the medical field, and as a result they have seen a massive uptick in use over the past 25 years. Indeed, nearly 200 unique biologic therapies have been approved since 1997, with nearly 60% of those being approved since 2014.
Biologics are revolutionizing the care of a variety of diseases across nearly every subspecialty. For example, there are currently six biologic therapies approved for the management of severe asthma. All have been shown to both reduce the incidence of exacerbations and to improve the recipient's quality of life compared to standard therapies. Indeed, these have been so effective that a collaborative effort among all asthma specialty societies recently published guidance on the clinical remission of asthma. Similarly, consider the case of ulcerative colitis and Crohn’s disease. For patients with even moderate IBD, biologics are the backbone of treatment with clear evidence showing their efficacy at inducing and maintaining remission. In addition, there’s the entire field of rheumatology, which is now dependent on biologic therapies to manage severe autoimmune diseases.
Furthermore, oncologic treatments have truly been revolutionized by the advances in biologic therapies. Today it is common to see patients who have been given monoclonal antibodies targeting T-cell lymphomas. One may also encounter patients who were administered revolutionary “checkpoint inhibitors” to empower their immune system to combat metastatic melanoma. One may even find other patients who received genetically modified T-cell therapies that specifically attack leukemia cells. Regardless of the application, these amazing medications allow us to target cancer — and limit damage to healthy tissue — in a way that has never been achieved with classic chemotherapy.
Most recently, we have seen huge strides in “gene therapies” which allow us to physically correct a patient's genetic code to treat diseases caused by a specific mutation. Consider sickle cell disease: in December 2023, the FDA approved the first ever gene therapies for patients age 12 and older. This is accomplished by first obtaining cells from a patient’s bone marrow, editing their genetic sequence, and transplanting these new “correct” cells back into the marrow so they can propagate. Similar therapies are approved for illnesses such as Duchenne muscular dystrophy, and ongoing research is underway to develop comparable therapies for cystic fibrosis.
The Perils of Biologics
Biologics are expensive. According to a report from the IQVIA Institute, the U.S. spent $260 billion on biologic therapies in 2021. This accounted for 46% of U.S. health care spending that year. These costs are expected to increase at least in the immediate future, as the U.S. has averaged a 12.5% yearly increase in spending on biologics over the past five years. This disproportionate number has raised some frustration among ethics groups, as biologics are only used by roughly 2% of patients in the U.S. Nevertheless, these effects are distributed to all payers, contributing to our already worst-in-the-world health care costs.
Additionally, the biologics revolution has completely restructured the world of drug discovery. A review showed that between 1991 and 2018, 39% of all drug discovery trials were related to biologics. This is remarkable when you consider that it wasn’t until the 2000s that we began to see a significant uptick in the use of biologics. This comes at the expense of small-molecule drug development (i.e., classical drugs) that are on the whole far further-reaching and much cheaper.
Apart from the structural issues surrounding biologics, there are important considerations for clinical practice as well. Namely, biologics are a relatively new set of medications with unique mechanisms, and sometimes unique adverse effects. Some of these effects are intuitive, such as the increased risk of infection for TNF-alpha inhibitors that lower the immune system. Others, such as the black box risk for gastrointestinal perforation for bevacizumab (an anti-cancer biologic), are less intuitive, and reflect how altering cellular mechanisms can have far-reaching consequences. Their unique effects speak to the need for increased clinical education regarding these medications.
A Plan for Biologics
Moving forward, how do we balance the promise and the perils? While they are not immune from some of the problems posed by traditional biologics, “biosimilar” agents represent a huge step forward in this biologic age. These are biologic agents that function similarly to a generic version of other medications. However, they are different from generic medications because they are distinct and novel molecules.
In 2015, the very first biosimilar agent was approved for use in the U.S. As of this year, there are 36 biosimilars approved for use in the U.S. with an average cost of 50% less than their counterpart molecules. This has equated to nearly $23.6 billion in savings since 2015. More so, these molecules are just as safe as their counterparts. A meta-analysis performed by the FDA in 2023 shows no difference in adverse events, mortality, or treatment discontinuation among patients who switched from biologics to a corresponding biosimilar.
However, there are still limitations to the latter’s wider adoption. For one, inadequate research has led to missed opportunities; currently, 86% of eligible biologics do not have a biosimilar under development. Additionally, these medications are marketed as distinct drugs because they are similar agents rather than generics. This leads to clinician hesitancy as it can feel like prescribing a different medication rather than an alternative.
Despite these drawbacks, however, there is no denying that biosimilars are the best available path to preserving these miracle drugs in a more sustainable way. As clinicians, we must embrace these medicines and consider them viable alternatives in our practice. Furthermore, we must leverage our collective efforts to ensure regulatory structures support their development. We must be stewards of these alternatives lest we find the miracle really was too good to be true.
Do you have any "miracle" success stories with biologics or biosimilars? Share in the comments!
Dr. Matthew Scott is a third-year internal medicine-pediatrics resident in Richmond, VA. He is passionate about advocacy, engaging with his community, and his newborn daughter. Dr. Scott is a 2023–2024 Doximity Op-Med Fellow.
Image by Crystal Eye Studio / Shutterstock
