By Kevin E. Noonan --
Insmed Inc. announced today that a just-completed clinical trial showed that its INS-19 product, a recombinant human granulocyte colony stimulating factor (G-CSF) was "bioequivalent" to Amgen's FDA-approved Neupogen®, a product used for treating neutropenia, a blood deficiency disorder associated with, inter alia, chemotherapeutic drug treatment.
One of the key points of contention over legislation permitting so-called "follow-on biologic" drugs (also termed "biosimilars") is the need for the drug to have the same safety, efficacy, and other characteristics of the innovator molecule. There is real reason for concern in this regard. Unlike conventional pharmaceuticals that are made using well-defined and controlled chemical reactions, biologic drugs are almost always made by a living cell (bacterial, yeast, or mammalian), and the cells used by the innovators are rarely available. Cells, even cells of the same type, are expected to have phenotypic variability that can influence the structure of the biologic drug product made by them. These differences can include differences in primary amino acid sequence (although this type of variability should be rare, in view of the possibility for significant changes in the biologic properties of such variants). The differences are more likely to be in post-translational processing, particularly in glycosylation patterns that are known to differ between different cell types (and may even differ between different strains or populations of the same cell type). It can also be expected that different formulations may have different properties. Potential consequences of this type of variability include changes in biovailability, biological activity, solubility (including the propensity for agglomerization), and immunogenicity.
Insmed's clinical trial was a "single-center, double-blind, two-way crossover bioequivalence" study, according to the company's press release. There were 32 healthy volunteers enrolled in the study, who were injected (randomly) with either INS-19 or Neupogen®, and then after a "washout" period dosed with the alternative drug product. The study reported maximum drug concentrations (Cmax) and total delivered drug concentrations (AUCs) in assessing bioequivalence of pharmacokinetic and pharmacodynamic responses.
The results reported by the company were that the Cmax values were nearly identical for INS-19 and Neupogen® (44.7 +/- 2.1 versus 45.5 +/- 1.9 ng/mL), and AUC values were 341 +/- 16 and 343 +/- 14 ng/mL hr, respectively. These values were reflected by a comparison of the response profile of neutrophil counts detected in blood samples after treatment with both drugs, which were "the same" according to the company.
Innovator biologics companies and their representatives (such as the Biotechnology Industry Organization, see "BIO CEO Provides Update on Patent Reform and Follow-on Biologics Legislation - Part II") have insisted that public safety requires human clinical trials to establish the safety and efficacy of follow-on biologic drugs, with strict post-approval surveillance. The "generic" biologics industry has opposed these strict requirements, maintaining that the requirements should be tailored to fit the particular biologic drug and to give FDA the flexibility needed to make such a determination on a case-by-case basis. Insmed's announcement represents the first demonstration that a follow-on biologic is bioequivalent to an innovator biologic drug.
Sales of Neupogen® in 2007 were approximately $1 billion.
For additional information regarding this or other related topics, please see:
• "Dr. Robert Shapiro Discusses Follow-on Biologics Report," February 19, 2008
• "Insmed Announces National Awareness Campaign Regarding Follow-on Biologics," February 13, 2008
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