by Howard Hochster, MD – In 2009 Congress passed the BPCIA (Biologics Price Competition and Innovation Act) to create an approval pathway for biologic compounds, meaning complex molecules which are not synthesized chemically but made by cells in culture and purified. These include monoclonal antibodies, proteins, and other macromolecules.
The idea behind this was to allow other manufacturers to develop a non-brand name (“originator”) version of the molecule at a cheaper price and the FDA has made this pathway available now for 19 compounds (including rheumatologics, and insulin) as well as oncology agents (trastuzumab, rituximab and bevacizumab).
Conceptually, these biosimilars require more data on their sequence, manufacturing, and post-translational modification than the originator compound, but only one clinical trial showing similar efficacy to the originator (which does not need to be a head to head comparison). So far, so good.
Unfortunately there are some “fine print” issues here which have made widespread use of these drugs impractical. First, all biosimilars are treated as individual drugs with their own identity, using the generic name followed by a four digit suffix (eg, filgrastim-sndz or Zarxio; bevacizumab-awwb or MVASI from Amgen).
This means that each agent must be ordered specifically and essentially makes them their own “branded” product. This is good, in that we can track which biosimilar is being used, but obviously rather different than the way we prescribe generics. More importantly, “interchangeability” or the ability to switch from one product to another in the middle of treatment is a separate category of approval and requires additional trials where the experimental arm includes medications being switched in mid treatment.
This may be practical for insulin which can be given for a short time with defined blood sugar measurements, but not so for drugs like trastuzumab or rituximab which are given long-term with patients going off for progression or toxicity.
Finally, without interchangeability each patient must be continued on the same compound as there is no approval for “switching in midstream” or for the pharmacy just changing products for the health system based on cost. No cancer pharmacy can reasonably keep multiple versions of bevacizumab on the shelves and track which patients get which “bevacizumab-xxxx” version.
This week the FDA issued the final guidance on interchangeability which did lower some of the barriers for drugs such as exclusive use of US marketed and approved product for switching studies and requiring additional studies on dosing errors. Some in Washington have argued that interchangeability is only about non-physicians substituting the biosimilar, since the doctor can order whichever biosimilar she wishes. However, let’s get real.
Doctors today work within large health systems or practices and order drugs in the EMR. Keeping a scorecard for which biosimilar four letter abbreviation is from Amgen, Boehringer, or Teva is not on anyone’s radar, nor is stocking multiple versions of a biologic and tracking individual patient utilization.
We need a better system here for use of biosimilars to actually achieve the goals of the BPCIA and to benefit health care consumers. FDA, please check the clinics and pharmacies for some practical insights.
Howard S. Hochster, MD
Distinguished Professor of Medicine, Rutgers Robert Wood Johnson Medical School
Rutgers-CINJ Associate Director, Clinical Research
Director Clinical Oncology Research, RWJ-B Health System
Rutgers Cancer institute of New Jersey
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