Table I
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Cumulatively, the years 2010 and 2011 witnessed the approval of 19 biopharmaceutical marketing applications by FDA in the
United States and EMA in the European Union combined (see Table I). 2010 was the better of the two years, with 13 total approvals.
While neither year compares favorably to 2009, during which 20 such products were approved, these approval numbers are in
line with average approval rates reported during the past several years (1–4). Products approved within the 2-year period
included 9 antibodies, 4 fusion proteins, and 3 enzymes, as well as an enzyme inhibitor, a hormone, and a colony stimulating
factor. Cancer and cancer-related conditions represented the principle indication (6 products), while the remaining products
target a wide variety of conditions.
In terms of expression systems used, 14 of the 19 newly approved products are produced using mammalian (mainly Chinese hamster
ovary, CHO) cell lines, two are expressed in Escherichia coli, while Saccharomyces cerevisiae, an insect cell-based expression system and a transgenic system is used to produce one product in each case. In overall terms,
these figures reflect the ongoing dominance of mammalian-based expression systems in biopharmaceutical manufacture.
Digging a little deeper reveals that only 11 of the 19 therapeutic proteins were genuinely new biomolecular entities approved
for the first time within the indicated timeframe. Three of the products (Actemra/RoActemra, Arzerra, and Victoza used to
treat rheumatoid arthritis, chronic lymphocytic leukemia, and type 2 diabetes, respectively), although newly approved in one
region over the past 2 years, had gained approval prior to 2010 in the other region (see Table I). Also approved, Nivestim
is a biosimilar product used to treat neutropenia; while Prolia, used to treat osteoporisis, and Xgeva, used to treat bone
loss associated with cancer, are effectively the same product with different indications. Lumizyme replaces the previously
approved Myozyme, used to treat Pompe disease, while Scintimun, although gaining EU-wide centralized marketing authorization
in 2010, had gained marketing authorizations in selected EU countries (the Czech Republic, Hungary, and Sweden) as far back
as 1994.
ANTIBODY PRODUCTS
Of the nine antibodies that made it to market, one is chimaeric, one is humanized, and six are fully human. The period also
witnessed the approval of a first generation murine antibody produced by traditional hybridoma technology (Scintimun). Such
first generation monoclonal antibody (mAb) products are more characteristic of the 1980s and early 1990s than they are of
this or indeed the past decade. Engineered antibodies (chimaeric/humanized/fully human) have predominated since that time
due to the characteristic clinical disadvantages exhibited by fully murine products (e.g., immunogenicity, the inability to
trigger effector functions in humans, and rapid removal from circulation). Given its in vivo diagnostic role (which does not rely upon triggering effector functions) and that it is radiolabeled, such characteristics
are less significant in the context of the product in question.
Adcetris is notable in that it is a (CD30-directed) antibody-drug conjugate (used to treat Hodgkin's lymphoma). The conjugated
toxin is monomethyl auristatin E (MMAE), an anticancer agent. On average, four molecules of MMAE are attached to each antibody
molecule. Binding of the antibody conjugate to CD30-expressing cells is followed by endocytotic internalization and subsequent
release of MMAE via proteolytic cleavage. MMAE is a microtubule disrupting agent. Binding to tubulin disrupts the microtubule network within
the cell, inducing cell cycle arrest and death by apoptosis.
