The biosimilars space offers significant commercial opportunity. About US$60 billion of branded biologic sales will lose patent protection over the next few years, including some of the largest-selling monoclonal antibodies (MAbs). Companies are jostling among themselves, each seeking the best position to exploit that opportunity. Regulators are creating and refining the necessary pathways to success, alliances are being forged, and companies are being acquired.
Despite the significant opportunity for biosimilar MAbs, significant risks remain. Perhaps the most significant of those is the potential for limited profitability, a concept that has not received sufficient coverage within the biosimilar debate. Biosimilar MAb profitability will be affected by longer-than-anticipated clinical development timelines, higher-than-expected sales and marketing costs, low physician adoption rates, aggressive competition from other biosimilar players, originator company pricing strategies, and originator lifecycle manag...
Current downstream processing strategies for recombinant proteins often require multiple chromatographic steps, which may lead to poor overall yields. Product purification can be especially difficult when a target protein displays reduced stability, forms isoforms or misprocessed variants, or needs to be purified from a complex mixture containing a high degree of contaminants.
One technology that has been developed to tackle such limitations is based on custom-made chromatography matrices containing camelid-based single-domain antibody fragments. With a molecular weight of only 12–15 kDa, these fragments are significantly smaller than conventional antibodies (with molecular weights 150–160 kDa). These consist of one peptide chain of ~110 amino acids, comprising a single monomeric variable domain of a camelid heavy-chain only antibody (VHH) (Figure 1).
Like in conventional VH, the core structure of a VHH immunoglobulin domain is formed by four framework regions. Three complementarity-determining regions (C...
+1The pressure to contain rising healthcare costs — combined with the number of innovator biologic drugs coming off patent (30 licensed biological drugs by 2015) — offers huge opportunities for developers of biosimilar products. In 2011, the global market size of the biosimilars industry was around US$2.5 billion. Global demand for such products — and monoclonal antibody (MAb) biosimilars, specifically — is estimated to grow at 8–17% from 2012 to 2016 (
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). The advent of biosimilars should bring more affordable biologics to market: Estimates of their costs range as much as 50–75% that of innovator biologics. That is especially important news to some developing countries where biopharmaceuticals have yet to become available.
Unlike a generic small molecule, however, a biosimilar product cannot be considered an identical copy of its innovator counterpart. Even very small differences in cell lines or manufacturing processes can have large impacts on potential side effects observed during treatment. Two “simil...
The BPI Theater is a 50-seat venue that for seven years has been located at the heart of the BioProcess Zone on the exhibition floor of the BIO International Convention. There, BPI provides attendees with four days of live presentations focusing on the latest scientific advances and business trends in biotherapeutic development and manufacturing. On Monday afternoon, 22 April 2013, Patricia Seymour of BioProcess Technology Consultants (BPTC) moderated a roundtable discussion on biosimilar development in the BPI Theater at BIO 2013 in Chicago, IL.
For a packed audience, she brought together four experts to provide valuable perspective: Uwe Bücheler of Boehringer Ingelheim, Richard Brudnick of Biogen Idec, Michiel Ultee of Laureate Biopharma, and Thomas Vanden Boom of Hospira. The “Introducing” boxes provide more information about each participant. Seymour’s own expertise covers development and commercialization of both biologics and small molecules, including supply chain strategy and operations leadership...
Concerns about the economic viability of biosimilars center on their high development cost relative to small-molecule generics, along with (and partly because of) the difficulty in demonstrating bioequivalence for these complex molecules. Immunogenicity is a particular area of increasing vigilance at both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) (
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). Unwanted immunogenicity is an underlying cause of multiple deleterious effects for all protein-based therapeutics — including loss of efficacy, altered pharmacokinetics, and reduced stability (
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) — and it poses a major risk for product failures and recalls.
Failure to demonstrate equivalent or (ideally) lower immunogenicity for a biosimilar is both costly and risky. Development of an unsatisfactory or inconsistent immunogenicity profile during development — or much worse, during postmarket surveillance — may be economically disastrous. It can even lead to costly reformulation work and addit...
No consensus concerning biosimilar-related terminology and definitions has yet been achieved (
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Biosimilars
may be defined as biopharmaceuticals slated for generic-drug–like, abbreviated, comparisons-based approvals through a formal biosimilar approval pathway in the United States, European Union, and/or other highly regulated and developed countries based on a demonstration of substantial (bio)similarity to a reference product.
As required in the United States, biosimilar active agents (those involving recombinant proteins) must be identical in primary sequence with their reference products. Analytical and comparative bioequivalence/pharmacokinetic (PK) clinical testing must support a lack of significant differences (particularly in efficacy and safety) between the biosimilar and the reference product.
Biosimilars
is also sometimes used to refer to biogenerics, including the ∼150 mostly lower-end “knock-offs” of established major-market innovator products not made to good manufacturing pr...
