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Challenges and Opportunities in the Era of Biosimilar Therapy

Washington, DC—The use of biosimilars offers great potential to reduce healthcare spending while expanding access to effective therapies for conditions such as rheumatoid arthritis. The numerous issues related to the development, regulation, reimbursement, and marketing of these agents were addressed by Candida Fratazzi, MD, President, BBCR Consulting, Cambridge, MA, at the 2016 Annual Meeting of the American College of Rheumatology.

Barriers to the Widespread Adoption of Biosimilars

Although the cost of developing biosimilars is approximately 10% the cost of developing biologics, the associated manufacturing costs of biosimilars is comparable, Dr Fratazzi said. The majority of trials for biologics also have challenges recruiting patients because researchers are more interested in trials of emerging biologics. Adding to recruitment issues is the sheer volume of trials that are competing for a limited number of patients willing or eligible to participate.

Another challenge facing the widespread adoption of biosimilars is that some individuals are uneasy about using these drugs, Dr Fratazzi said. A European survey found that only 31% of respondents would be “fully confident” about being treated with a biosimilar, even if their treating physician explained the drug to them. To counter this, some countries, such as the United Kingdom and the Netherlands, have invested resources for the validation of biosimilars in the marketplace by promoting clinical studies designed to answer physicians’ and patients’ apprehension.

One of the greatest challenges in the use of biosimilars is related to regulation, especially when it comes to verifying that the safety and efficacy of these agents is comparable to their reference products. Dr Fratazzi mentioned that regulatory agencies in the United States operate differently from those in other parts of the world.

“Currently, interchangeability is a unique prerogative of the US Food and Drug Administration,” she said. “Indeed, the European Medicines Agency cannot mandate interchangeability.”

In Europe, interchangeability is determined on a country-by-country basis, and not through a regulatory agency. There needs to be strict standards and regulations followed when manufacturing biologics, because structural or process-related impurities may potentially impact the efficacy and safety of complex biologic agents, such as monoclonal antibodies and biotherapeutic proteins.

Advantages of Biosimilars

One of the major advantages to using biosimilars is that they may reduce costs and provide patients with access to a very effective class of biologic drugs. However, the difference in price between biosimilars and innovator biologics can vary greatly from one country to another, based on the success of a particular country’s negotiations with drug manufacturers. For example, in Norway, biosimilars can cost up to 70% less than their innovator counterparts but the price difference in the United States is expected to be approximately 20% to 30% lower.

Nevertheless, even a 20% price difference for the 5 most popular patent-free biologics would translate to ~1.6 billion euros in annual savings across Europe. Experts have predicted that in the United States, biosimilars will lead to a $44.2-billion reduction in direct spending on biologic drugs from 2014 to 2024, or approximately 4% of total spending on biologics in the same time period. Dr Fratazzi predicted that even greater savings will be seen as more manufacturers market these agents.

She also discussed immunogenicity, which may be an issue with any protein-based therapeutic. Antidrug antibodies (ADAs) can be transient, which is the rationale for measuring ADAs several times in the course of a clinical trial. The assay used to measure ADAs must be product-specific, and strict validation studies are required to ensure the sensitivity and specificity of assays. Dr Fratazzi emphasized that rates of immunogenicity should not be compared across trials if the patient populations, sample collections, and assays are not the same. She also noted that researchers need to study immunogenicity in the target patient population because factors such as previous exposure to biologics or concurrent medications may impact immunogenicity outcomes.

“Immunogenicity is an element of uncertainty that can only be assessed in clinical trials,” she noted.

Dr Fratazzi said that switching trials will bolster the acceptance of biologics for reasons beyond issues of interchangeability, and that she advocates the initiation of more switching trials to guide evidence-based clinical practice. She acknowledged that noninferiority switching trials have complex study designs that need to enroll large cohorts of patients, making them expensive and also challenging to execute, since there is a nonnegligible possibility of study failure.

Although very few randomized switching trials have been initiated, in clinical practice, switching between biologics is not uncommon. Clinicians may choose this option because it is more convenient, or because it can improve efficacy and decrease toxicity. Dr Fratazzi emphasized the importance of overcoming existing challenges related to biosimilars because these agents can offer significant advantages to patients.

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