[Ip-health] PLoS Speaking of Medicine Blog-FDA Voucher for Leishmaniasis Treatment: Can Both Patients and Companies Win?

Rachel Cohen rachel.cohen72 at gmail.com
Wed Jan 21 11:44:58 PST 2015



FDA Voucher for Leishmaniasis Treatment: Can Both Patients and Companies

By  <http://blogs.plos.org/speakingofmedicine/author/plos_guest_blogger/>
Bernard Pécoul and Manica Balasegaram
Posted: January 20, 2015


Bernard Pécoul and Manica Balasegaram discuss whether drug companies have
taken advantage of flaws in the FDA Priority Review Voucher program.


It sounded like a pure global health success story.

A company develops a drug for one of the most neglected diseases. As a
reward, the company receives a voucher from the U.S. Food and Drug
Administration (FDA). The company then sells this voucher, allowing the
buyer to “fast-track” FDA approval for another product. A “win-win” in its
truest sense: Innovation is rewarded while patients suffering from a deadly
illness are given access to the fruits of scientific innovation.

There are problems with this story, though.

What if the company did not actually develop the drug in question? What if
patient access to the drug is far from secure?

When it was created in 2007, the FDA Priority Review Voucher (PRV) program
came with hopes that it could incentivize research and development (R&D) for
neglected diseases. Under the initial legislation, a developer that receives
FDA approval for a drug to treat one
hap9-subchapV-partA-sec360n.htm> of 16 diseases is eligible for a PRV, which
allows the bearer to speed up approval for a drug application of their
choice, or sell the voucher for another company to use. This reduces
approval time from ten months on average to six – a crucial window for
companies to get drugs on the market earlier than their competitors.


Only three vouchers for neglected diseases have been granted since 2007, the
latest of which was in March 2014 to Knight Therapeutics, for registering
the leishmaniasis drug miltefosine in the United States. In November 2014,
er-to-gilead-tsx-gud-1969777.htm> sold the voucher to Gilead for $125
million. While there was a great deal of media attention on the
record-breaking sale price of this voucher, something seemed lost in the
discussion: patient needs.


Some 350 million people are at risk of leishmaniasis with up to 40,000
deaths a year from the disease’s visceral form. Current drugs are costly,
toxic and difficult to administer.

Miltefosine is one of only a handful of drugs that are recommended by the
World Health Organization (WHO) for the disease. It is not “new.”
6_miltefosine_pl_deriv.pdf> Miltefosine was discovered in the 1980s and the
R&D for its use against leishmaniasis was conducted in the 1990s by the WHO
and partners.
review-voucher-program-msfs-ruis-explains/> Miltefosine then changed hands
numerous times: from Zentaris to Paladin to Endo.


Knight Therapeutics was created from Endo in early 2014 with a sole product
registered: Impavido® (miltefosine). By the time Knight sold its PRV, most
R&D costs had been borne by other public and private actors.
-vaccines-1.2153534> Knight’s CFO recently said that FDA approval cost about
$10 million, which seems to be the only significant investment that Knight
has made for this drug.


Meanwhile, patient access to miltefosine is extremely fragile.

Paladin and Endo maintain exclusive distribution and manufacturing rights to
distribute miltefosine, while Knight Therapeutics holds the license in the

The WHO established a preferential price with Zentaris in the mid-2000s for
developing countries. However,
large minimum purchasing requirements were put in place by the company.  In
our struggle to access affordable miltefosine, Doctors Without
Borders/Médecins Sans Frontières (MSF) and the Drugs for Neglected Diseases
initiative (DNDi) have had to purchase far more supply than needed in order
to be eligible for the preferential price. Supply shortages have been
recorded in several countries.


Even in the US patient access is far from secure. A recent New York Times
-solved/?_r=0> describes an American woman’s unsuccessful attempt to access
miltefosine after contracting the cutaneous form of leishmaniasis in Brazil.


In mid-December 2014,
ial-Ebola-Incentive-Program-Into-Law/> President Barack Obama signed into
law an amendment to the PRV program, adding Ebola to the list of eligible
diseases and making the voucher easier to transfer among companies. But more
reforms are needed to correct the PRV’s fundamental flaws – companies should
not be rewarded for R&D they did not carry out while patients struggle for


In the short-term, we must address the
l> worrying issues that hinder access to affordable miltefosine, at least
until better treatments for leishmaniasis become available. Manufacturers
and license holders of miltefosine must be transparent about the production
costs of the drug while pricing it at-cost or with a minimal profit margin
to ensure sustainable production.
tml> Additional clinical studies must be supported to optimize its use.


Congress must fix the PRV so that it truly incentivizes R&D, and does not
simply reward the registration of an existing drug. And companies should be
required to ensure affordable access to any new treatment that receives a
PRV. Miltefosine isn’t the first time that a PRV has been gamed and awarded
for a drug already in use in developing countries. In 2009, Novartis
was awarded a PRV for Coartem®, which had been in use for some time for
malaria in Africa. Price barriers are not new either: Janssen received
efully-coexist> a PRV for the tuberculosis drug bedaquiline, but the drug is
unaffordable for most developing countries.


Innovative incentive mechanisms for neglected disease R&D have enormous
potential, but the real winners should be patients – not only companies.


Bernard Pécoul, MD, MPH, is the Executive Director of the Drugs for
Neglected Diseases initiative (DNDi)

Manica Balasegaram, MD, is the Executive Director of the MSF Access Campaign


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