As biologics patent periods approach their end, manufacturers have sought approval for combination-drug therapies and conjugates that will generate revenue despite eventual biosimilar market competition with key agents like trastuzumab, Nelson notes.3

That might complicate the regulatory picture for clinical substitutions with biosimilars, he tells Cancer Therapy Advisor.

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“If the biosimilar applicant can provide enough data and a robust enough showing, it should be entitled to an approval that extrapolates across all the indications for which the reference product is approved. [But,] if it doesn’t make enough of a showing that it should be approved for all indications, then FDA will only approve it for a subset of indications and will restrict the labeling.”

That means that regulatory approvals for combined use of trastuzumab [BF1] with other drugs won’t necessarily automatically apply to regulatory approvals for biosimilars, Nelson explains.

“But as a practical matter, physicians may choose to take advantage of potential cost savings for biosimilars by prescribing the biosimilar of trastuzumab in the combination,” Nelson is quick to note. “In the end, the physician will do what he or she feels is in the best interest of the patient.”

With recent expansions in many states’ Medicaid public health insurance programs, there will be pressure on state lawmakers to facilitate the prescribing and substitution of less-expensive biosimilars for branded biologics. But state legislators are already being heavily lobbied by biologics manufacturers to block automatic substitution at pharmacies.

“Despite the fact that the first biosimilar applications were only first filed a few months ago and we haven’t yet had an approval, there have already been efforts in about 25 states to legislate automatic substitution of biosimilars,” Nelson notes. “Most of the proposed legislation has been to prevent substitution of a biosimilar for a branded biologic. Those efforts, however, have been largely unsuccessful.”

Instead, state legislatures have been requiring notification of physicians when substitutions are made.

Of the eight states that have thus far passed legislation regulating biosimilars substitution, North Dakota’s is the most restrictive, allowing substitutions only for biosimilars found to be interchangeable, Nelson says.

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“Most of these states require notification of the physician and/or the patient if there is a substitution, and some states require patient consent before any substitution,” he noted.

Florida’s substitution law does not require physician notification for substitutions. California’s legislature passed a substitution bill in 2013 but it was vetoed by Gov. Jerry Brown, Nelson explained.

Despite evolving state-level practices and inevitable delays associated with regulatory ambiguities’ resolution by the courts, Nelson says he remains optimistic about the future of biosimilars in clinical oncology and the innovation expiring biologics patents will facilitate.

“Competition breeds innovation,” Nelson said. “Patent expiration, along with the continued testing of the biosimilar pathway, will lead to more intense development of additional and better anticancer biologics.”


  1. U.S. Food and Drug Administration (FDA). Drugs: Information for health care professionals (biosimilars).
    . Updated September 9, 2014. Accessed December 11, 2014.
  2. Paradise J. Battle lines drawn over biosimilar application and patent disclosure process. Health Affairs Blog. Published November 17, 2014. Accessed December 11, 2014.
  3. Nelson KM, Gallagher GC. Biosimilars lining up to compete with Herceptin: opportunity knocks. Expert Opin Ther Patents. 2014;24(11):1149-1153.