[Ip-health] Goozner: Coartem and the FDA Priority Review Voucher

[robert weissman]

 From Merrill Goozner's Gooznews
http://www.gooznews.com
Nov 7, 2008

Are economic incentives necessary to get the private sector to do the
right thing? Cities and states offer corporations tax breaks to locate
in impoverished areas. Companies get tax breaks to beef up their
research and development portfolios. In health care, some physicians get
extra pay if they adhere to clinical practice guidelines under the
presumption that it will lead to better patient outcomes.

But these thinly-veiled bribery strategies often come with unintended
consequences. The companies that get the tax breaks may have located or
invested in those areas anyway. Individuals or companies that get the
extra payments find ways to meet the criteria without actually
delivering the desired result.

The unintended consequences of an ill-conceived incentive scheme will be
on full display in early December when Novartis goes before a Food and
Drug Administration advisory committee seeking U.S. approval for its
anti-malarial combination pill Coartem. (see
http://www.fda.gov/cder/audiences/acspage/meetings/aiac_20081203.htm)

FDA approval is not in doubt. Coartem, a combination of an artemisinin
extract and lumefantrine, was approved in Switzerland after decades of
extensive clinical trials in the developing world. The World Health
Organization placed artemisinin-combination therapy on its preferred
therapy list for drug-resistant malaria in 2002. (For the complete story
on the development of this new wonder drug, derived from ancient Chinese
medicine, see the December 2006 cover story of The Scientist magazine.)

So why is Novartis seeking U.S. approval now? It is not as if the U.S.
has suddenly experienced a major malaria outbreak.

The only possible reason is an incentive scheme slipped into the FDA
Amendments Act last year by Republican Sen. Sam Brownback of Kansas. The
"Tropical Disease Priority Review Voucher" law gives any company that
develops a new drug for neglected diseases of the developing world a
"priority review" voucher that can be used for any other drug brought
before the agency.

Under the Prescription Drug User Fee Act, priority reviews are given to
drugs that represent a significant advance in medical therapy. The FDA
has only six months to review those priority applications. But under
standard reviews, which are given drugs that replicate the action of
drugs already on the market, the agency's short-handed staff can take up
to two years to conduct its examination of the clinical trial evidence
behind the new drug application.

Novartis' application for the artemether/lumefantrine combination has
itself been given a priority review because neither drug has been
approved by the FDA. When I called a spokesman for the Swiss-based firm
yesterday to inquire about the reasons for submitting its application,
he suggested the approval would make the drug available for the
travelers market. He admitted, however, that no new clinical trials in
this first world population have been conducted, and its documentation
would rely on previous trials conducted in the developing world.

Might the priority review voucher be the reason for the company's going
to the expense of seeking FDA approval, I asked. "It is our
understanding that we are eligible for the priority review voucher," he
said.

According to the FDA's draft Guidance for Industry on Tropical Disease
Priority Review Vouchers, published in October, companies have the
choice of using the voucher for one of its own standard drug
applications; or, it could be sold to another firm.

What might it be worth? If a company uses it for a potentially
blockbuster me-too drug that replaces a billion dollar seller, the extra
6 to 18 months of patent life won through the priority review could be
worth anywhere from $500 million to $1.5 billion.

There are no protections in the draft guidance against abuse of this new
incentive. The new drug need only be for a tropical disease like
malaria, tuberculosis or leishmaniasis (the full list is in the
guideline; the FDA will hold a hearing in December on expanding the
list); have no active ingredient that has been previously approved by
the FDA; and must itself qualify for a priority review.

So let's tally the costs and benefits of this new incentive scheme as
applied to Coartem. The developing world gets nothing, since this
combination pill for malaria is already on the market. Meanwhile, first
world consumers down the road will be paying from $500 million to $1.5
billion extra for a heavily marketed drug that from the moment it comes
on the market will be no better than other available therapies.

A few years ago, the Global Alliance for TB Drug Development estimated
the cost of developing a new antibiotic for tuberculosis at $259
million, including the cost of capital and the cost of failures. Let's
assume that the figure has since inflated to twice that level. If
consumers could directly pay the money this priority review voucher will
take out of their pockets into a special fund to finance research in
neglected diseases, sick people of the developing world would
potentially get one to three new drugs to fight TB.

Of course, R&D is never a given. TB patients might get nothing from
another $1.5 billion poured into research. But, with this first use of
the priority review voucher system, that's what they'll be getting anyway.

Merrill Goozner
mgoozner@starpower.net