Biologics
BIOLOGIC First-in-class
PIPELINE RISK High
DEVELOPMENT COST
High
POTENTIAL BENEFITS
First-generation therapy with a novel mechanism of action
Biosuperior Medium Medium to High
Improvements in key drug attributes (efficacy, safety, dosing) over original brand
Biosimilar Low Low to Medium
Lower price versus original innovation
Table 1
for example, represented a game changer over standard therapies, offering a more targeted approach to cancer management. Rather than killing cells indiscriminately, oncologists now have therapies that can turn off pathogenic pathways, activate apoptosis signalling, or even down regu- late signal pathways. Clearly, the stakes to develop first-in-class biologics are high, but so are the potential rewards.
On the opposite side of the spectrum are biosim- ilars. These compounds are associated with the lowest risk to a pipeline portfolio, as they essen- tially copy an existing biologic molecule. Sometimes called a ‘follow-on biologic’, ‘subse- quent entry biologic’ or ‘similar biotherapeutic product’, a biosimilar is intended to be as much like the original therapy as possible. In recent years, some simple biosimilar drugs, such as insulin, erythropoietin and interferon have been successfully developed and launched. However, for complex biologics, such as monoclonal antibodies or Fc fusion proteins, given their high complexity and the unique manufacturing processes, the path- way to a generic biologic can often be as cumber- some as the original product. Unlike the relatively quick development and approval process for gener- ic pharmaceuticals, most follow-on biologics must undergo clinical trial testing to demonstrate com- parability to the original therapy. This includes showing that the profile of the copy exactly repli- cates, or is at least similar to, the innovator prod- uct’s characteristics, including pharmacokinetics, mechanism of action and route of administration. There is a risk that subtle changes may cause the generic molecule to perform differently. Like a biosimilar, a biosuperior drug is devel- oped against an already established biological tar- get that has been validated in human clinical tri- als. But that is where the similarities end. A biosu-
Drug Discovery World Spring 2011
perior is intended to have attributes that are better than the first-generation product, rather than being a carbon copy. The overall pipeline portfo- lio risk with a biosuperior is higher than with a biosimilar, but less than the innovator product because the goal is to demonstrate an improve- ment over the existing treatment based on already validated targets.
A biosuperior utilises cutting-edge technologies such as protein engineering, and novel drug for- mulation and delivery approaches to enable its superiority over a first-generation product, possi- bly improving its efficacy or safety profile or improving administration route or reducing dosing frequency. In particular, a few technologies offer great promise for biosuperior antibodies, including affinity maturation, effector function enhance- ment, half-life extension through Fc engineering, bi-specific, and antibody-drug conjugate technolo- gy. Ideally, a biosuperior has the potential to become a best-in-class product because it is yield- ing benefits beyond the innovator product. Given these loftier research goals of a biosuperior, R&D costs will run higher than for a biosimilar, although the investment is not nearly as significant as devel- oping a first-generation product.
Finding the right mix Today, many pharmaceutical companies are rac- ing to become early entrants in the biosimilar marketplace. Biosimilars represent an opportuni- ty for a manufacturer to enter a new category, and realise an economic return with a relatively small investment. At the same time, incorporating biosimilars into a pipeline also reduces the port- folio’s overall risk. Currently, there are more than a dozen companies that have developed a biosim- ilar, or are working on products to enter the biosimilar market.
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