A BIOBETTER APPROACH
In contrast to the regulations for biosimilars, the route to approval for a biobetter is clear. A full biological licence
application (BLA) will be required in the US, and the equivalent procedure will be required in other markets. The cost of
bringing a new product through the BLA process has been estimated at $1.24 billion (13). This figure, however, incorporates
a 30% success rate for molecules entering the process. With biobetters, it is arguable that the success rate will be significantly
higher because the target and efficacy of the originator product are known. Thus, failures during the development period will
be due to unwanted side effects, as opposed to lack of efficacy. The average development costs for a biobetter will therefore
be closer to the estimated direct costs for a single product of $375 million.
As each modified molecule progresses through the development process, more is learned about the effect of the modifications,
and this knowledge can then be applied to the design of studies to test subsequent molecules. As a result, companies can further
improve success rates by developing platform technologies. Using consistent platforms also reduces manufacturing design costs
and can simplify the analytical characterization program. A typical example of the platform approach is the carboxy terminal
peptide attachment developed by Washington University in St Louis, MO. Merck brought a follicle-stimulating hormone (FSH)
modified in this way to the European market as Elonva. Prolor Biotech is using the technology as well, to develop modified
HGH (Phase I completed), Interferon (preclinical), Factors VII and IX (preclinical), EPO (preclinical) and other therapeutic
peptides. The platform approach is also readily applicable to antibodies. MedImmune and Xencor are among those modifying amino
acid sequences in the Fc domain to develop biobetter versions of existing monoclonal treatments.
Platform approaches also allow smaller companies to enter the market. By developing and protecting the technology of the modification,
such companies can enter partnerships with larger organizations that have the necessary production, distribution, and sales
capability, rather than funding the full development package themselves.
If the costs of bringing a biobetter to market are two- to fourfold higher than those of a biosimilar, what are the advantages?
The most obvious is that the product will be new, and therefore subject to 12 years of market exclusivity in the US. In Europe
and other markets, exclusivity is more closely aligned with patent protection. The data from the European experience of biosimilar
competition presented above suggest that biosimilar competition will be weak, and thus a long period of exclusivity may not
be as necessary for profit generation as would be expected. The benefits to the license holder will be earned by the nature
of the product; its improved characteristics must be used to attract patients and increase sales. While the biosimilar aims
to take market share by being slightly cheaper than the originator, the biobetter has to gain market share on merit alone.
Sales presentation of a newly approved biobetter will thus extol the benefits of the product rather than relying on price
alone to drive business.
What are the potential benefits to patients? The main intention of the BPCIA was to drive down costs of biologics to the healthcare
system, recognizing that biologics will form an increasing component of the drug expenditures and have high relative treatment
costs compared with traditional small molecules. The Federal Trade Commission report estimated that the introduction of biosimilars
represented a potential savings of 10%–30% (8). Given the European experience of biosimilar uptake and the effect of biosimilar
introduction on originator price, the overall impact on the drugs bill for a particular indication where biosimilar treatment
becomes available is likely to be a 10–20% reduction (8).
A biobetter will command a premium price for its improved characteristics, but the improved dosing regimes common to such
products can result in significant cost savings for the treatment of a particular indication. For example, based on the treatment
used in a pivotal trial for Neulasta—an Amgen biobetter version of their own Neupogen—a single treatment cycle costs $3400
for Neulasta and $6000 for Neupogen, despite the unit prices being $3400 and approximately $300 (body weight dependent), respectively
(14). The biobetter in this case represents a 40% reduction in overall costs for the healthcare provider.