Because the development and marketing of biosimilar drugs is much more demanding than it is for traditional generic drugs,
the number and types of players entering the market will be limited.
In 2007, Sandoz (Holzkirchen, Germany) was the first company to launch a biosimilar—Omnitrope (human growth hormone)—in Europe.
Although Omnitrope failed to gain significant market share, the move enabled Sandoz to establish itself as a major biosimilars
player in an industry where gaining physicians' trust is as important as price. The company reinforced its position by being
the first to launch biosimilar epoetin in 2007. Sandoz's parent company Novartis (Basel) lends it the marketing experience
and infrastructure of a branded organization.
It is unsurprising that Teva (Petach Tikva, Israel), one of the largest generic-drug companies in the world, is looking to
establish itself in the biosimilar arena. Although the company is initially concentrating on Europe, it perceives the US biosimilars
market as a genuine, albeit tougher, opportunity and expects it to boom in the middle of the next decade (8). Teva has three
biologic manufacturing facilities and sells biosimilar interferon alpha 2b in some of the less-regulated markets such as China
and Lithuania. In partnership with Savient Pharmaceuticals (East Brunswick, NJ), Teva markets Tev-Tropin (recombinant human
growth hormone) in the US. Many view the product as a biosimilar despite the fact it was granted full approval.
Branded pharmaceutical companies.
Some branded biologic companies have begun to produce biosimilars in hopes of maintaining their market share. Manufacturing
biosimilars would be relatively quick and easy for most branded companies. In December 2008, Merck & Co. (Whitehouse Station,
NJ), AstraZeneca (London), and Eli Lilly (Indianapolis, IN) announced their intention to enter the biosimilars arena. Merck
& Co. plans to launch six biosimilars between 2012 and 2017 (9).
All three companies are using the biotech expertise they gained through acquisitions. Merck & Co. acquired GlycoFi in 2006,
whose technology enables control of glycosylation during biopharmaceutical production. Merck bought the biosimilars portfolio
of Insmed, which includes drugs for patients undergoing chemotherapy, in February 2009. AstraZeneca acquired MedImmune, whose
products include the FluMist influenza vaccine, in 2007, and Eli Lilly acquired ImClone, maker of the Erbitux cancer therapy,
The importance of an established marketing presence has particular significance for biosimilars because companies need to
assure physicians that their products are as safe and efficacious as branded products. Initial adoption will greatly depend
on physicians' opinions. Companies that already have relationships with physicians will have an edge over smaller enterprises
focused on small-molecule generic drugs for whom marketing is less important. As a result, branded pharmaceutical companies
will be able to take advantage of their marketing infrastructure and their reputation to promote acceptance.
GlaxoSmithKline and Johnson & Johnson.
Although Glaxo-SmithKline (London) produces biologics and aims to establish a biopharmaceuticals operation, the company decided
that biosimilars are a high-risk venture that requires too much investment for too little return, at least for the present
(10). Johnson & Johnson (New Brunswick, NJ) has taken a similar line, stating that the considerable investment required for
conducting clinical trials would drive up costs excessively (11).
The US outlook
Cutting healthcare spending by promoting generic drugs and biosimilars is at the heart of President Obama's healthcare agenda
(12). One of the biggest hurdles to a biosimilars pathway, however is determining the marketing exclusivity period for branded
biologics. Branded biologics manufacturers state that 14 years is required to recoup costs, stimulate innovation, and attract
future investors. The Generic Pharmaceutical Association strongly opposes this view and instead favors an exclusivity period
of three to five years (13). Obama has voiced support for a seven-year exclusivity period.
On March 17, 2009, Rep. Anna G. Eshoo (D-CA) introduced a biosimilars bill titled the Pathway for Biosimilars Act (HR 1548)
in the House of Representatives. The bill's goal was to provide the US Food and Drug Administration with a process to review
and approve biosimilars. The issues of interchangeability and market exclusivity were highly contentious. The Eshoo bill provides
12 years of data exclusivity for a new biologic and extends that period to 14 years if the biologic is approved for a new
indication during the first eight years after its original approval. The bill includes a six-month exclusivity period for
pediatric use. The Eshoo bill also requires new clinical trials comparing the immunogenicity of the biosimilar to that of
the branded biologic to be submitted in the biosimilar approval application.
The Eshoo bill, which was favored by small- and large-molecule innovator companies, gained strong bipartisan support in the
House. The bill gained further momentum when the Senate HELP Committee approved an amendment that incorporated the Eshoo bill's
key principles, including a minimum of 12 years' data exclusivity for biologics. In July 2009, the House included the Eshoo
bill in its healthcare-reform legislation, marking another step forward toward a US regulatory pathway for biosimilars (4).