[Ip-health] Biogenerics, Not Just Biosimilars

[Sarah Rimmington]

An excellent story by Merrill Goozner about a key issue surrounding the
creation of a pathway for U.S. FDA approval of follow-on biologic drugs.

http://www.gooznews.com/archives/001272.html#more
December 14, 2008
Biogenerics, Not Just Biosimilars

The debate over a regulatory pathway for biotechnology generic drugs is
shaping up and it doesn=92t look good for cost-conscious patients or
anyone pulling their hair out over rising health care costs.

Last week, both Merck and Eli Lilly announced plans to expand their
biotechnology divisions. While they are taking aim at proteins already
on the market, both companies told the press that their new biotech
drugs would not be generics in the traditional sense. They will be
slightly modified versions of existing drugs that will be run through
the full panoply of clinical effectiveness testing and sold at prices
much closer to the original drug.

In essence, both companies are banking that the =93biosimilar=94 legislatio=
n
that now seems destined to pass Congress next year will bring into
existence a biotechnology me-too industry. That=92s very different than a
true generic industry, which was created by the Hatch-Waxman Act of 1984
for small-molecule drugs.

Unlike true generics, which are exactly like the original drug, me-too
drugs contain slight modifications that qualify for their own patent
protection. Their clinical usefulness may be no different or only
slightly improved from the original. But, because they have been put
through their own clinical trials and have patent protection, they can
be marketed to physicians as unique products and priced accordingly.

The results are often of marginal benefit to patients, consumers and
health care plans. Me-toos are usually priced within 10 to 20 percent of
the original drug=92s price, and sometimes cost more if they have
marketable benefits like less frequent dosing. True generics, on the
other hand, usually cost less than half of the original molecule because
multiple firms jump into the fray and there is no direct-to-consumer or
direct-to-physician marketing to inflate costs.

Merck told the Wall Street Journal that its first target was Amgen's
Aranesp, an appropriate choice given that it is the original biotech
me-too drug that racked up $3.6 billion in sales last year. The only
reason it hasn=92t wound up in a patent infringement case like every other
company that has ever tried to market copycat versions of Amgen=92s
flagship biotech products is that the company also owns the original
molecule =96 Epogen.

How does Aranesp differ from Epogen? The company added a few sugars to
the original molecule so it would stay in the blood stream longer and
require less frequent dosing. This improvement never mattered to
dialysis patients, who were the sole market for Epogen, because the drug
is intravenously administered during thrice-weekly dialysis sessions.

But they weren=92t whom Aranesp was aimed at in any case. Amgen developed
the drug to compete with Johnson & Johnson=92s Procrit, which is Epogen
with a different label. Amgen gave away the non-dialysis markets (cancer
and AIDS patients =96 eventually a much larger population) to J&J in the
1980s to raise money for its original clinical trials. (The red blood
cell stimulating drugs are collectively known as erythropoiesis
stimulating agents or ESAs or sometimes just EPO because they have
epoietin in their generic name.)

Several companies besides Amgen tried to make their own versions of EPO.
But they ran afoul of the nation=92s patent laws, at least as interpreted
by the federal district court in Boston where all Amgen=92s patent
litigation has been heard by the same judge over the past two decades.
Transkaryotic Therapies, a small biotech startup now merged out of
existence, lost to Amgen on a patent infringement suit against its
version of EPO produced by human cells (Amgen uses Chinese hamster ovary
cells). And last year, Roche=92s EPO version called Mircera, which has
been engineered to stay in the blood stream for a month, lost another
patent infringement case brought by Amgen even though it is being widely
used in Europe, which already has adopted biosimilar legislation.

Indeed, a month after the patent slapdown, Roche won Food and Drug
Administration approval for the drug after a standard review (reserved
for drugs not considered a major improvement in existing therapy). So
Mircera is safe, it=92s effective, and it=92s less costly because patients
need only visit their physicians=92 offices once a month. It just can=92t b=
e
sold in the U.S.

The European approach to approving Mircera holds lessons for Americans =96
if legislators on Capitol Hill choose to pay attention. Biosimilar
approval guidelines issued by the European Medicines Agency (EMEA)
require only that companies wishing to manufacture generic biotech
products show their molecules have the same physical properties (how
they react in the body and how the body breaks them down) and the same
acute toxicological safety profile.

The companies bringing biogenerics to market must also monitor patients
who take them to ensure they are working properly and there are no
hidden dangers in the particular cell line used to make the generic.
There is nothing in the EMEA guidance that calls for clinical
effectiveness testing.

That=92s very different from the biosimilar bills introduced in Congress
in the current session. Sen. Ted Kennedy=92s S.1695, Sen. Judd Gregg=92s
S.1505 and Rep. Anna Eshoo=92s H.R.5629 each call for testing drugs for
safety, purity and =93potency.=94 The FDA uses potency as a synonym for
efficacy. In other words, all three bills would mandate clinical trial
effectiveness testing =96 the expensive second and third-stage trials not
required under Hatch-Waxman for traditional generics.

If Congress forces biosimilars to go through that additional step, it
will be creating a me-too industry, not a generic biotech industry.
Companies like Merck and Lilly will be able to get into that game. But
they will have the same costly clinical trials and costly marketing as
innovator firms, and the price breaks for consumers will be minimal.

Of course, companies wishing to market me-too biosimilars like Roche=92s
Mircera will still have to get over the patent hurdle. Amgen=92s patent on
Aranesp, for instance, doesn=92t run out until 2024. Before Roche can
market Mircera in the U.S. as a biosimilar, the logic that Judge William
Young used in his Boston rulings =96 involving if I understand it properly
secondary and tertiary process and use patents =96 will have to be undone
in the law.

That won=92t be an easy fight, either. David Beier, who used to work for
Al Gore and is now Amgen's senior vice president for global government
affairs, told the Journal "protection of intellectual property" is "an
essential component" of any biosimilar legislation.

Clearly, it=92s going to take a lot of consumer and payer pressure to get
legislation that offers fast and meaningful economic relief from the
high cost of biotech drugs when their patents expire. Changes in patent
law to enable a me-too biosimilar industry isn't even half a loaf. What
the public needs is a pathway to biogenerics that doesn't require
costly, duplicative clinical trials.

Posted by gooznews at December 14, 2008 02:39 PM

About the author:
MERRILL GOOZNER spent more than 25 years in the news business as a
foreign correspondent, economics writer and investigative reporter for
the Chicago Tribune and other publications. Goozner left daily
journalism in June 2000 to teach journalism at New York University. In
December 2003, he joined the Center for Science in the Public Interest
as director of the Integrity in Science project, where he continues his
research and writing. The views expressed on this web site are Goozner's
personal views and do not necessarily reflect the views of CSPI.

--
Sarah Rimmington
Attorney
Essential Action, Access to Medicines Project
Washington, DC
Tel: (202) 387-8030
Cell: (202) 422-2687
www.essentialaction.org/access/