Biologics remain a significant force in the life sciences industry as they represent only 2% of the pharmaceutical market but account for 37% of all drug spending. Even though a limited number of biologics are available now compared to small-molecule drugs, as patents expire, biosimilars gain popularity, and drug development advances, the market is on the verge of a significant shift. With blockbuster biologic drug patents expiring in 2023, more biosimilars will enter the market than in any previous year. In part one of this two-part blog series, we discussed three of the five therapeutic areas transformed by biologics. In this final part of the series, we examine how biologics have impacted ophthalmology and oncology. Even though biologics have significantly affected additional therapeutic areas, biologics utilized within these five therapeutic areas have improved patient outcomes immensely. Biologics are medications derived from living sources such as bacteria, yeast, and animal cells. Biosimilars are also medications containing biological products, but biosimilars use a reference product (the original biologic) to formulate the new therapy. Since biologics and biosimilars contain biological compounds, each batch contains inherent variations and requires precision in handling. However, biosimilars are “highly similar” and clinically equivalent to their reference product. With the biologic market’s evolution imminent, medical affairs specialists and medical science liaisons must understand how biologics affect patients in the present and the future. According to Precedence Research, the global biologics market will reach $719.84 billion by 2030. As the development and adoption of biologics is unlikely to slow down, biologics and biosimilar knowledge will become increasingly relevant for life science professionals. Over the past few years, biologics have experienced rapid growth due to improvements in drug development and increased funding. Currently, there are 621 biologics with FDA approval, with oncology biologics growing at the fastest rate. Figure 1 displays critical milestones in the ophthalmology and oncology biologics markets. The significance of these biologics and emerging biosimilars is discussed in this post.Figure 1: Major Milestones for Biologics in Ophthalmology and Oncology in the Past 32 Years

1. Ophthalmology Biologics have significantly improved outcomes for patients with corneal, conjunctival, and retinal diseases. In addition to treating ocular diseases, biologics have improved outcomes for patients suffering from systemic conditions with ocular manifestations such as inflammatory bowel disease, psoriasis, ankylosing spondylitis, and migraines. As a result, biologics have replaced older medications such as steroids, which have more side effects.Biologics have dramatically improved the prognosis for patients suffering from the following ocular diseases:

• Giant cell arteritis
• Neurotrophic keratopathy
• Exudative age-related macular degeneration
• Uveitis
• Graves’ disease
• Inherited forms of blindness

In 2017, Luxturna® (voretigene neparvovec-rzyl) became the first prescription gene therapy for patients with an inherited retinal disease caused by mutations in both copies of the RPE65 gene. Diagnosis requires genetic testing, but once diagnosed patients have dramatically improved on the biologic therapy.In January 2020, the introduction of the biologic Tepezza® revolutionized the treatment of Graves' disease, as it is the first medication to reduce the eye bulging caused by thyroid disease. Additionally, Tepezza® reduces eye pain and enhances functional vision. Although the treatment is a significant breakthrough in treating thyroid eye disease (TED), the cost is a significant limiting factor, as three vials cost $46,000. Tepezza® is given through IV infusions once every three weeks for an 8-week course. In 2006, patients with retinal diseases benefited from the approval of Lucentis®, a biologic therapy for retinopathies, including macular degeneration. Lucentis® became a blockbuster drug with billions in revenue. However, over recent years, other biologics have entered the market. Eylea® is now the top earner, with sales of $9.4 billion in 2021. On , the first ophthalmology biosimilar approved in the U.S, Byooviz® (ranibizumab-nuna), became commercially available. is a monoclonal antibody medication and vascular endothelial growth factor (VEGF) inhibitor (anti-VEGF). VEGF is responsible for promoting the growth of new blood vessels. The biosimilar if it is too much or if the vessels forming are deleterious. (ranibizumab-nuna) treats several retinal vascular disorders, including diabetic retinopathy, wet age-related macular degeneration (wet AMD), and retinal vascular occlusions.Whether the new biosimilar will reduce the cost of biologics for retinopathies (i.e., Lucentis® and Eylea®) remains to be seen. There are significant barriers biosimilars must overcome, including provider and patient hesitation., Aside from ophthalmology, biologics have transformed oncology, giving hope to patients with previously untreatable forms of cancer. According to the (GCO), cancer cases will rise from 19.3 million in 2020 to 28.4 million by 2025. Increasing demand and advances in drug development are accelerating cancer research. As one of the leading causes of death worldwide, research continues to pursue novel methods to fight cancer, including more effective immunotherapy therapies. aims to restore or enhance immune-system function or counteract cancer-induced immunosuppressive signals. Immunotherapy is one of the most common ways to combat cancer cells however new therapies are emerging, including:

• gene therapy
• adoptive T-cell transfer therapy
• oncolytic virus therapy

In 1990, the FDA approved the first oncology biologic, Bacillus Calmette-Guérin (BCG), a non-virulent form of a live tuberculosis bacterium used to treat bladder cancer. After BCG therapy, about 70% of patients with bladder cancer experience remission. The mechanism of BCG is not well understood, but BCG therapy is currently under investigation to target other forms of cancer. Undoubtedly, the most well-known oncology biologic is Keytruda®, which received accelerated FDA approval in 2017 and has become a blockbuster drug with billions in revenue for Merck. As the first oncology drug approved based on a biomarker rather than a tumor's location, Keytruda® has helped millions of patients fight cancer.Keytruda’s indications span 16 types of cancer, including the following:

• Melanoma
• Non-Small Cell Lung Cancer (NSCLC)
• Head and Neck Squamous Cell Cancer (HNSCC)
• Triple-Negative Breast Cancer (TNBC)
• Esophageal Cancer
• Gastric Cancer

However, Keytruda® is an extremely expensive drug creating access challenges for many cancer patients. With Keytruda®'s patent set to expire in 2028, biosimilars will flood the market in the next few years. The availability of biosimilars for cancer patients will potentially reduce access challenges.5As the oncology market continues to expand, innovation and clinical trials are occurring at an increasing rate. More oncology clinical trials occurred in 2021 than in any previous year, and oncology drugs are increasingly receiving accelerated FDA approvals.4 The use of biologics is not slowing down, especially for some forms of cancer. Today, 80% of melanoma patients are treated with biologics.

Source: Iqvia Institute. Global Oncology Trends 2022 Outlook to 2026.

The Future of Biologics

As the demand for innovative therapies increases and patent extensions for branded biologics expire, the global biologics market will thrive. Additionally, advances in drug development will boost the market. However, biologics will continue to require real-world evidence (RWE) to demonstrate their effectiveness.1 Establishing yourself as a biologics and biosimilars expert will help ensure you are ready for the next era of the life sciences industry. The ACMA will offer the first ever board certification in biologics and biosimilars in Fall 2022. Visit the resources below to learn more. 

Biologics Resources

• Join the waitlist for the ACMA’S Board Certification in Biologics and Biosimilars (BCBBSTM) program
• Learn more about the BCBBSTM program
• Read 5 Reasons Why Biologics Remain Expensive
• Explore the National Comprehensive Cancer Network Drugs & Biologics Compendium
• Consult the FDA's Purple Book Database of Licensed Biological Products

References 1. Arondekar B, Duh MS, Bhak RH, et al.. Real-World Evidence in Support of Oncology Product Registration: A Systematic Review of New Drug Application and Biologics License Application Approvals from 2015–2020. Clinical Cancer Research. 2022;28(1):27-35. doi:10.1158/1078-0432.ccr-21-2639.2. Cardinal Health. 2022 Biosimilars Report: The U.S. Journey and Path Ahead.; 2022. https://www.cardinalhealth.com/content/dam/corp/web/documents/Report/cardinal-health-2022-biosimilars-report.pdf3. Kapur M, Nirula S, Naik MP. Future of anti-VEGF: biosimilars and biobetters. Int J Retina Vitreous. 2022;8(1):2. doi:10.1186/s40942-021-00343-3.4. Kinch MS. An overview of FDA-approved biologics medicines. Drug Discov Today. 2015;20(4):393-398. doi:10.1016/j.drudis.2014.09.003.5. Kvien TK, Patel K, Strand V. The cost savings of biosimilars can help increase patient access and lift the financial burden of health care systems. Semin Arthritis Rheum. 2022;52:151939. doi:10.1016/j.semarthrit.2021.11.009.6. Lexchin J. Affordable Biologics for All. JAMA Network Open. 2020;3(4):e204753. doi:10.1001/jamanetworkopen.2020.4753.7. Woo SJ, Veith M, Hamouz J, et al. Efficacy and Safety of a Proposed Ranibizumab Biosimilar Product vs. a Reference Ranibizumab Product for Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial. JAMA Ophthalmol. 2021;139(1):68-76. doi:10.1001/jamaophthalmol.2020.5053.