Interchangeability

Some believe that the ability of pharmacists to substitute a biosimilar for a branded biological is vital to promoting biosimilars and creating a viable market. Given the novelty, the inherent molecular complexity, and the associated safety concerns about biosimilar drugs, automatic substitution or interchangeability will not occur in the short term. Sufficient clinical data may be generated to make interchangeability a possibility in the long term. All of the five major European markets (France, Germany, Italy, Spain, and the UK) have banned automatic biosimilar substitution. Physicians in the UK are encouraged to prescribe brand-name biologics. The Eshoo bill does not permit outright interchangeability and recommends that FDA issue guidance on this topic.

The advent of the biosimilars market has spawned a flurry of ill-defined terms to describe the relationship between bio-similars and their reference products. Although EMEA focuses on comparability and not interchangeability, the US bills make a distinction between the two. FDA defines interchangeability as "the situation where scientific data convincingly demonstrate that two products with very similar molecular compositions or active ingredient(s) can be safely substituted for one another and have the same biologic response and not create adverse health outcomes" (14). Therefore, automatic substitution, which has spurred the growth of the generics market, is unlikely to have a prominent role in biosimilars uptake in Europe or the US.

The first biosimilars introduced to the market represented the low-hanging fruit of the biologics world. They were relatively simple molecules with established safety profiles, compared with mAbs, which have considerably higher barriers to entry. Although mAbs are currently the most profitable biologics, biosimilar mAbs are still a long way off. In addition to their complexity and the hurdles to their manufacture, mAbs still enjoy patent protection because they were introduced fairly recently (15).

At least three Indian companies have launched or are developing mAbs. Dr. Reddy's (Hyderabad, India) and Biocon (Bangalore, India) both brought biosimilar versions of Roche's (Basel) Rituximab to market. Specialty generic-drug company Zenotech Laboratories (Hyderabad, India) claims to be developing a range of at least six biosimilar versions of mAbs already, including Rituximab (which is ready to enter Phase III) and Herceptin (trastuzumab) (16). The degree to which these monoclonals are similar to their respective reference products is unclear, and the products would warrant considerably more clinical testing before approval in any of the major markets.

Biologics such as Amgen's (Thousand Oaks, CA) rheumatoid arthritis drug Enbrel (etanercept) are expected to lose sales to biosimilars earlier than will mAbs. The market for biosimilar Enbrel is potentially more lucrative than that for first-generation biosimilars, and its high cost is already prompting payers to limit drug use in markets such as that in the UK. A biosimilar could therefore erode not only sales of branded Enbrel, but also sales of newer branded competitors (17).

Undoubtedly, the level of biosimilars adoption will have as much to do with the outcome of a public relations battle as with practical matters such as biosimilars' price and performance compared with those of biologics. Competition from biosimilars manufacturers will prompt innovator companies to modify their strategies to sustain revenue growth. Attaining biotech expertise through partnering and acquisitions will be one technique for success, but some branded companies will solidify their own presence in the biologics space. Regardless of the approach, product-positioning strategies will be imperative in a market where building reputation and trust among physicians, patients, and payers will be key to acceptance in the short term.

Bornadata Bain, PhD, is the director of strategic development for healthcare at Datamonitor, 111 Devonshire St., Boston, MA 02109, tel. 617.722.4606, fax 617.523.6993, bbain@datamonitor.com