| At
the Financial Times' Global Biotech Conference, held in
London on October 20 2004, industry experts gathered to
discuss key issues facing the biotechnology industry. Two
presentations and a panel discussion were devoted to one
of the hottest topics - biogenerics.
These
are copies of biological products, such as erythropoietin,
interferon or human growth hormone, which are now some of
the most lucrative in the world. Johnson & Johnson's
EPO products for anaemia, Procrit and Eprex
(originally developed by Amgen), alone had sales of $4.1
billion in the 12 months to June 2004, according to IMS
MIDAS data - making it the world's eighth
best-selling pharmaceutical product.
Australia
clears Sandoz hGH
The
success of biopharmaceuticals has made generic firms keen
to launch cheaper copies - but they have met with frustration
as the major regulatory agencies have yet to finalise appropriate
routes
for their approval. Unlike small molecules, biological
products can be affected by their production process - a
factor the developers have used to lobby against biogenerics.
The
FDA has been considering the matter over the summer of 2004,
and the EC has passed legislation for the approval of "similar
biological medicinal products" that is due to take effect
in late 2005. Biogeneric applications can already be made
to the EMEA, and on October 25, BioPartners submitted an
MAA for an alpha-interferon product for the treatment of
hepatitis C (similar to Schering-Plough's Intron A
and Roche's Roferon-A). Moreover, on October 4, the
Australian Therapeutic Goods Administration approved Omnitrope,
a biogeneric form of recombinant DNA human growth hormone
from Novartis' generics unit Sandoz. So, perhaps biogenerics
are finally getting nearer the market...?
Teva
describes the "battleground"
As Israel
Makov, President and CEO of Teva, the world's largest generics
manufacturer, told the FT conference, biogenerics have become
a battleground and now is a pivotal time for the biotechnology
industry. He noted that for traditional pharmaceuticals,
lost patents and expired exclusivity periods provide an
incentive for companies to develop new products - an incentive
that was missing in the biotech industry; 70% of FDA-approved
small molecules have generic counterparts, whereas Epogen/Procrit
could have 28 years of exclusivity if its patents do not
expire until 2017 - something no small molecule would have.
On a more
emotional note, he pointed out that many patients could
not afford expensive biological drugs, while on a larger
scale biogenerics could lead to "dramatic" savings for the
healthcare system. The stakes are huge: worldwide sales
of biological products could reach $50 billion in 2004,
representing 10-15% of the total
pharmaceutical market. Biologics also represent approximately
one-quarter of the total industry's pipeline. Moreover,
the top 10 biotech companies have a market share of 84%,
versus 51% for the top 10 pharma firms - and because many
only have one or two key products, they are prepared to
fight tooth and nail to protect them.
Manufacturing
issues dominate
As Makov
pointed out, the stakes are also significant for generic
manufacturers, which have to make a series of investments
to produce biogenerics. But he commented that Teva would
gladly assume patient management costs to assure them that
its products were truly equivalent to the brand.
He also
shot down some of the widely held misconceptions about biogenerics,
for example that products could not be adequately characterised,
or that manufacturing processes affected the final product
- what about all the changes the developers have made to
their production methods?
Using
hGH as an example, Makov highlighted that five companies
currently produce it, all using different production systems,
yet in theory all the products (worth $1.7 billion annually
according to IMS) are equivalent to pituitary hGH. And in
his opinion, Biogen Idec's multiple sclerosis therapy Avonex
(interferon beta-1a) was granted FDA approval with an abbreviated
application - a Phase I bioequivalence study - as most of
the clinical trials had used a different version.
hGH
market share
(12 months to June 2004)
Source: IMS MIDAS
Patrick
Vink, Global Head of Biopharmaceuticals at Sandoz, then
took up the baton. Stating that he had moved into the generics
industry from big biotech himself, Vink described the arrival
of biogenerics as a logical step in the evolution of the
biotech industry, and expressed some exasperation at the
regulatory delays: one whole session of the recent FDA workshop
was devoted to what to call the products (the verdict was
'comparable biologics').
Referring
to the issue of bioequivalence, Vink said there was no point
in exposing patients to unnecessary clinical trials by duplicating
them to win approval for biogenerics. He did, however, say
that bioequivalence testing would have to be decided on
a case-by-case basis in a process that would need to be
discussed by the industry and regulators. Like Makov, he
said the science was in place, Sandoz was merely waiting
for some regulatory clarity.
He also
echoed Makov in remarking on the investments that Sandoz
would need to make in biological products, in terms of manufacturing
and R&D. Biogenerics might also need a higher level
of marketing than traditional generics, to demonstrate their
benefits to physicians and insurers.
Why
weren't problems foreseen?
For
the panel discussion, led by conference chair Martyn Postle,
CEO of Cambridge Healthcare and Biotech, Makov and Vink
were joined by Radan Spaventi, Chief Scientific Officer
of Pliva, a major generic manufacturer based in Croatia.
One question was why the generic industry had not foreseen
the lack of a regulatory pathway for biological products.
The panellists put forward a number of reasons:
- a
very young industry presented difficulties for regulators
- generic
firms struggled with the science, and perhaps focused
too much on manufacturing rather than regulatory issues
- strong
lobbying from the biotech industry
They
all stressed that the approval process was the key issue.
As Makov stated, if regulators ask for significant trials,
biogenerics could become 'me-too' products - i.e. not significantly
cheaper than the original brand because of the high development
costs (traditional generics are sometimes as little as 10%
of the brand price). Moreover, if they were me-toos,
promotional costs would be higher, as doctors would have
to choose between different versions of the same molecule.
Another
delegate asked if antibody products were also being copied.
While the generic executives did not see any reason why
not in the future, at the moment they are focusing on simpler
proteins like hGH or GCSF (Neupogen), for which analytics
are already available. Generic antibodies, however, could
be in the pipeline in time for the first patent expiries
of major products like Herceptin (trastuzumab) and
Rituxan (rituximab).
The
final question was timelines: when did the panel foresee
the first biogeneric launches? Makov believed it would be
some time this decade, while Vink noted that some less regulated
markets, such as China, already had them - and took heart
from Australia's approval of his company's Omnitrope hGH
product.
So,
the generic manufacturers are geared up and ready to go
- all they need is a green light from the regulatory agencies.
This article
was written by Selena Class, Deputy Executive Editor of
IMS
Company Profiles, which covers a number
of leading generic and biotech companies. IMS
Generic Planning and IMS
Generic Market Analyzer can provide
further insight into current and future generic opportunities:
for further information about any of these publications,
please contact Rupesh Chudasama via e-mail
or call +44 207 393 5136. |
