most of the world. In less regulated markets “similar biologics” have been in use for years. The highly regulated markets
of the EU, Australia, Japan and Canada have had biosimilar
guidelines in place since 2005, 2008, 2009 and 2010 respectively. The EU currently has 16 authorized biosimilars including the first monoclonal antibody approval for a biosimilar
infliximab. There are 9 authorized biosimilars in Australia.
Japan has 6 authorized biosimilars including a mAb and
Canada has 3 authorized biosimilars including a mAb. With
the passing of the BPCIA, the doors have opened in the US.
BIOSIMILAR COMPETITION IN THE US
Competition in the US biosimilars market will be unlike
competition in any other segment of the pharmaceuticals for
multiple reasons. First, there are high costs associated with the
development, approval and commercialization of biosimilars.
Second, biosimilars are not automatically substituted yet, which
will require biosimilar companies to invest in organization and
strategies commonly associated with a brand company. Third,
with no biosimilar approved in the US, there is a lack of understanding of these products across all areas of the health care
sector. Lastly, the interchangeability designation will disrupt
any norms created by a biosimilar-only market. Additionally,
many deals have been struck to fill competency gaps among
partners, creating interesting competitor profiles.
There are numerous competitors vying for the US market
which fall into three categories. First, innovator companies
which have diversified into biosimilars like Amgen and Pfizer.
Second, traditional generics manufacturers which have expanded into biosimilars like Hospira and Teva. And third, companies created solely to provide better access to patients for
complex biologics such as Therapeutic Proteins International.
In the US, two biosimilar applications have been filed. In
addition, the FDA tentatively approved a copy version of
Lantus. Because Lantus was not originally filed as a BLA, an
NDA/505(b)( 2) pathway had to be pursued even though the
product was filed as a clinically and analytically equivalent
molecule or what would be considered biosimilar.
Sandoz is currently the leading name in biosimilars. The
company has three biosimilars marketed in highly regulated
markets ex-US and six late stage molecules. In July 2014 Sandoz
announced the FDA had accepted its biosimilar application for
filgrastim, the first biosimilar application accepted by the FDA.
The second biosimilar application in the US was for a biosimilar infliximab from South Korean company Celltrion. The
product received approval from the EMA in October 2013 and
is marketed in the EU under the name Remsima. In March,
Celltrion filed two declaratory judgment suits against patents
related to infliximab, which demonstrates the intellectual property considerations that will be prevalent in this space.
Boehringer Ingelheim, one of the most established bio-manufacturing companies, confirmed plans to develop
versions of adalimumab, bevacizumab and rituximab in its
annual conference this past April. Currently, the company
is running two clinical trials for its biosimilar rituximab (BI
695500), a phase I trial in follicular lymphoma and a phase
III trial in rheumatoid arthritis. In addition, Boehringer
initiated a phase III study for BI 695501, a version of adalimumab. Boehringer and Lilly partnered to create a copy insulin glargine which was tentatively approved by the FDA.
Other innovator biologics competitors have biosimilar pipelines but have not yet announced any FDA filings. Amgen has
products in development on its own and with partner Actavis,
including a completed Phase III for adalimumab and Phase III
studies in progress for trastuzumab, bevacizumab and rituximab. Pfizer has multiple biosimilar products in development
including adalimumab, infliximab and trastuzumab.
Hospira partnered with Celltrion for multiple products including infliximab, which has EU approval under the name
Inflectra. Hospira has announced they intend to bring a biosimilar version of Epogen to the US before August of 2015.
Teva received approval for tbo-filgrastim, brand name
Granix, through the BLA route and is not considered a biosimilar in the US. The company announced it would withdraw its
balugrastim BLA for FDA consideration. Recent moves contrast
with Teva’s initial plans for presence in the space including a
joint venture with Lonza to develop a biosimilar version of rituximab which was discontinued in July of 2013.
One untraditional player in the emerging biosimilars market
is Samsung, who first entered the market by building a bioman-ufacturing facility for contract service opportunities. Eventually,
the Korean company started the Bioepis unit and entered into
partnerships with both Biogen Idec and Merck to bring biosimilar versions of monoclonal antibodies to market. Currently
Samsung Bioepis has multiple products in varying stages of
clinical development including infliximab (SB2), trastuzumab
(SB3), etanercept (SB4) and adalimumab (SB5).
It is clear to see that the US market will be a highly competitive one with remaining uncertainty on how biosimilars
will be treated once approved and launched. The driving
factor in the forefront should be expanded access to more
affordable options for patients. ■
PHARMACEUTICAL PROCESSING | NOV/DEC 2014 21 ■
Exhibit B: Four levels of similarity