Opportunities and Challenges in the Era of Biosimilars

On the final day at ACR 2016, Dr. Candida Fratazzi delivered a comprehensive overview of emerging biosimilars in therapeutic management. She addressed several topics that are on the minds of many clinicians as the treatment landscape is evolving now that biosimilars are here. These included the opportunities and challenges facing biosimilars entering the market, issues related to immunogenicity and interchangeability, and switching studies.

A common misperception is that biosimilars are like generics for biologic therapies. Dr. Fratazzi pointed out that although the cost of development of biosimilars is roughly one tenth that of innovator biologics, manufacturing costs are comparable, and biosimilars face some unique R&D challenges. She stated that 85% of biologics have faced difficulties recruiting patients for their trials for various reasons, including investigators being more interested in participating in trials of new biologics than trials involving biosimilars, and because of the overall large number of trials vying for a limited patient pool.

One of the key opportunities for biosimilars is that they offer the potential to reduce costs and increase access of patients to the very effective class of biologic medications in general. However, different countries negotiate with drug manufacturers and the result is that the price differential between biosimilars and innovator biologics can vary widely from one country to another. For example, in Norway, costs of biosimilars are up to 70% less than their innovator counterparts, whereas in the US, it is expected that most biosimilars will be priced ~20-30% lower. Nevertheless, even a 20% price differential for the 5 most popular patent-free biologics would amount to ~1.6 billion euros in annual savings across Europe. Over a 10-year time frame, studies suggest the adoption of biosimilars could save ~$44.2 billion in the US, which currently accounts for 50% of the total biologics market. Dr. Fratazzi predicted that as more competitors enter the market, bigger discounts will be seen.

Dr. Fratazzi addressed the complex issue of immunogenicity, which can affect any protein-based therapeutic. Anti-drug antibodies (ADAs) can be transient and thus it is important to measure ADAs at multiple time points during a treatment trial. The assay used to measure ADAs must be product-specific, and rigorous validation studies are needed to ensure assay sensitivity and specificity. Dr. Fratazzi noted that is it inappropriate to compare rates of immunogenicity across studies that used different assays in different patient populations and with different schedules for sample collection. She also highlighted the importance of studying immunogenicity in the target patient population (not only healthy controls) since patient characteristics including concomitant medications and prior biologics exposure can influence immunogenicity outcomes.

To date, very few randomized switching trials have been undertaken. Nevertheless, switching between biologics routinely occurs in clinical practice (e.g. switching between different agents within a class such as anti-TNFs, or between classes with different targets such as from an anti-TNF to anti-IL-6) due to loss of efficacy, safety/tolerability, or convenience. Dr. Fratazzi commented that switching trials will be very important for market acceptance for reasons beyond issues of interchangeability, and she advocated for more switching trials to guide evidence-based clinical practice. She acknowledged that non-inferiority switching trials have complex study designs that require large numbers of patients, making them costly and also risky to undertake, since there is a non-negligible possibility of study failure.

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