Key Considerations in Bringing a Biosimilar Drug to Market


There are several ongoing global phase 3 clinical trials for biosimilar adalimumab, which treats conditions such as rheumatoid arthritis, psoriatic arthritis, and Crohn's Disease.

To ensure the successful clinical development of a biosimilar, early consultation with regulatory agencies is critical.

It is also important to have ongoing consultation during the course of the development program to make adjustments, since the totality of the evidence will be used for regulatory approval, according to a study published in RMD Open.

Adalimumab (Humira) is the world’s top-selling prescription drug, with indications approved in more than 87 countries: rheumatoid arthritis (RA), plaque psoriasis

(PsO), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease (CD) and ulcerative colitis (UC).

Since the patent for adalimumab will expire in 2016 for the United States and in 2018 for most European countries, multiple drug companies are developing biosimilar versions of adalimumab. One entry, Exemptia (Zydus Cadila) was recently approved in India, with approvals currently under discussion in the US (FDA) and Europe (European Medicines Agency (EMA).

Currently, there are 9 global phase 3 clinical trials for a biosimilar adalimumab, 8 of which are completed or recruiting. A joint trial by Sandoz and Novartis is currently ongoing.

Approval Parameters for Biosimilars

As specified by the FDA and EMA, these studies are not required to establish the clinical efficacy of the biosimilar product in every approved indication of adalimumab, but to demonstrate biosimilarity in safety and efficacy. This represents a great advantage to biosimilar developers in terms of reduced cost and shortened time to regulatory approval, the study noted.

It may be possible to conduct the pivotal study in one indication to demonstrate biosimilarity in clinical efficacy and safety in order to obtain regulatory approval and request extrapolation across indications. However, a decision should be made regarding which indication(s) to pursue in the pivotal efficacy trial(s) and in potential supportive trials.

This includes what strategy to adopt in order to obtain approval for all indications of the reference product (extrapolation of indication), the researchers wrote.

Parameters that influence this decision are multidimensional, comprising regulatory sentiments, scientific considerations, operational demands, and commercialization interests. In fact, on the basis of EMA and FDA guidance, extrapolation to other approved indications of the reference product could be acceptable, but needs to be scientifically justified, according to the study.


In addition to the choice of therapeutic indication and extrapolation of the indication, other considerations important for designing the pivotal clinical trial of a biosimilar discussed in this report are summarized below. These include:

  • Study design Targeted patient population (eg, disease activity, prior biological treatment)
  • Background therapy
  • Stratification factors
  • Transition design
  • Primary end point
  • Choice of equivalence versus non-inferiority design
  • Defining equivalence margin

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