[Ip-health] Devex: Zika vaccine could be delayed, unaffordable after US Army grants exclusive rights to pharma company

Zack Struver zack.struver at keionline.org
Fri Jan 27 08:47:16 PST 2017


Zika vaccine could be delayed, unaffordable after US Army grants exclusive
rights to pharma company

By Sophie Edwards | 27 January 2017

The U.S. Army’s plan to grant exclusive rights to a promising Zika vaccine
to a major pharmaceutical company has raised questions about whether that
threatens its future affordability and availability to people in developing

The purified, inactivated Zika virus vaccine — called ZP IV — has been
developed by the U.S. Army and is currently in its first phase of testing
at the Walter Reed Army Institute of Research in Maryland and the National
Institutes of Health.

If it successfully passes clinical trials, the vaccine would have the
potential to halt the spread of the virus, transmitted by mosquitoes and
sexual intercourse, which has been reported in 69 countries since 2015,
including the United States, and is linked to serious birth defects in

The deal was posted by the Army on the public Federal Register in December
and will give Sanofi Pasteur, the vaccine unit of French multinational
pharmaceutical company Sanofi, exclusive access to the new vaccine
technology, which has been developed and paid for by the U.S. government.
In return, Sanofi will take on the role of conducting clinical trials,
getting regulatory approval, manufacturing and distributing the vaccine.

The humanitarian aid organization Médecins Sans Frontières has criticized
the Army’s decision to grant Sanofi the patent license, which will give the
company an exclusive right to make, use and sell the vaccine for 20 years,
as well as 12 years of marketing and data exclusivity even after the patent
has expired. MSF is saying this will give the company a monopoly on the
drug and thus no incentive to make it affordable. Sanofi could also choose
to stop developing the vaccine if it decides it is commercially

MSF wants the U.S. Army to consider granting an “open nonexclusive” patent
license instead, opening up the technology to other pharmaceutical
companies for testing and development. MSF argues this will increase
competition and thus bring down the price and ensure the vaccine reaches
those who need it in middle-income and developing countries.

“Ministries of Health and people around the world will only be able to
benefit from the U.S. government investment if the resulting vaccine is
effective, safe, available, affordable and suitably adapted to the
resource-limited settings where most people affected by Zika virus live,”
MSF said in a statement.

“The next step in the Zika vaccine development process, including its
licensing and technology transfer strategy, needs to ensure that U.S.
government funding and leadership in vaccine R&D results in a vaccine that
is effective and accessible for all patients in need in the U.S. and
globally, including the most neglected,” the group added.

The United Nations High Level Panel on Access to Medicines, formed in 2015
to address the lack of access to medicines in many developing countries,
appears to agree with MSF’s recommendations. In its 2016 report, the panel
said: “Universities and research institutions that receive public funding
must prioritize public health objectives over financial returns in their
patenting and licensing practices,” and listed the use of nonexclusive
licenses, the donation of IP rights, and taking part in public sector
patent pools as potential mechanisms by which to do this.

Sanofi has responded by saying it’s assuming “financial and opportunity
risks” by partnering with the government on Zika as there is no guarantee
of a commercial market for the vaccine.

“...we’re still assuming financial and opportunity risks because there is
no clear path to commercialization at this time, as the epidemiology of
this infectious disease is still a moving target,” according to Sanofi’s
research and development project lead, Jon Heinrichs.

The U.S. Army told Devex in an email statement: “We believe granting an
exclusive license in this case is reasonable and necessary to most quickly
and most safely provide this potential vaccine for public use to combat the
growing international threat of the Zika virus.”

Unusually, the U.S. Army has requested to extend the time period for
comments on the announcement in the Federal Register by an additional 45
days until mid-March, the second time the comment period has been extended,
to allow time to compose written responses to the submissions.

Experts have predicted the Zika market could be worth more than $1 billion
a year, driven by U.S. and European travelers willing to pay high prices
for such vaccines, Reuters reported in October.

Sanofi is part of a race to develop a Zika vaccine

The ZP IV vaccine — which is thought to be the furthest along in terms of
development in the Zika vaccine field — is developed from the inactivated
Zika virus. The vaccine was shown to give 100 percent protection against
the Zika virus in mice, according to a study published in science journal
Nature last August.

Sanofi is not alone in working on the Zika virus vaccine. It is not even
the only drug company to receive U.S. government funding to work on the
issue; GlaxoSmithKline has partnered with the NIH to evaluate a new vaccine
technology for Zika known as SAM (self-amplifying mRNA), and Japanese
company Takeda has also entered the vaccine hunt with $312 million funding
from BARDA.

Another group of concerned organizations — including Knowledge Ecology
International, a nonprofit that lobbies to increase access to medicines —
have also written to the Army to complain about the Sanofi deal.

KEI says Sanofi does not need to be incentivized to develop the vaccine and
take it to the market — the standard justification for granting such
exclusive licenses — since the candidate vaccine has already received
“extensive government subsidies” and is extremely likely to get additional

“The grant of the exclusive rights in the patent is an unnecessary
incentive to bring the invention to practical application because of the
significant federal funding in the clinical trials and the grant of
additional exclusivities and subsidies,” KEI said.

In September, BARDA — the U.S. Biomedical Advanced Research and Development
Authority, a unit within the U.S. Department of Health and Human Services —
gave Sanofi $43.2 million “for phase II development and manufacturing” of
the Zika vaccine, according to a Sanofi press release.

KEI communications and research associate Zack Struver explained that if
approved, Sanofi will also earn a priority review voucher from the U.S.
Food and Drug Administration, which it could “sell on for millions of
dollars,” and so already has “sufficient incentive” to develop the vaccine
with or without the exclusive license, he said.

Priority review vouchers are designed to speed up the review process for
new drug products and thus incentivize drug companies to work to develop
treatments for rare diseases or those without a robust market. Vouchers are
transferable and have been sold to other companies for upwards of $300

However, the statement from the U.S. Army said there was a strong case for
granting Sanofi exclusive rights to the technology, due to competition from
the “many” groups working on a Zika vaccine. Sanofi is taking on “risk” by
accruing the license since there is a “long way to go in terms of time and
money” before a Zika vaccine can be approved, they said. Furthermore, the
army is also yet to receive the patent from the U.S. Patent and Trademark
Office, and there is a chance it “may never issue,” adding more “risk” for

“The federal government needs a non-federal partner with the research and
production capabilities and the willingness to invest their own substantial
funding to most quickly get this product to the market and available for
public use,” the spokesperson added.

The KEI letter to the army also asks for four conditions to be imposed on
the licensing agreement.  These include requiring Sanofi to limit the price
of the vaccine to “no more than the median price being charged in other
high income countries;” limiting the length of time that Sanofi has
exclusive rights to the technology, requiring the vaccine be made
“available and affordable” in developing countries; and requiring Sanofi to
be transparent about the costs of research and development.

The U.S. Army responded by saying the license agreement has stipulations in
place to “protect the public interest,” including the option to terminate
if Sanofi fails to “bring the invention to practical application within a
reasonable time,” or “make the benefits of the invention reasonably
accessible to the public.”

Sanofi says no “clear path to commercialization” for Zika at this time

The pharmaceutical company says that even with the public funding from
BARDA, taking ZP IV through the many stages of testing, approval and
manufacturing requires Sanofi to take on “financial and opportunity risks”
due to the fact Zika is “still a moving target” and there is “no clear path
to commercialization at this time,” according to Heinrichs, Sanofi’s
research and development project lead.

“We have modeled various commercial scenarios including current endemic
areas, spread to other geographies and the travel market, among others. The
nature of the epidemiology and spread of the virus will impact the degree
of profitability,” Heinrichs said.

Sanofi may have a point, according to Paul Wilson, assistant professor of
clinical population and family health at Columbia University’s Mailman
School of Public Health, who says there is “genuine uncertainty”
surrounding how big the Zika problem will be and how widely a vaccine would
be used. This is compounded, he said, by the fact that the virus could
ultimately become widespread but “without causing harm,” or even die out as
people become immune.

If this turns out to be the case, however, MSF’s and KEI’s concerns may be
valid since Sanofi would likely lose interest in the project and fail to
drive the vaccine all the way through development, WIlson said.

“I’m sympathetic to MSF’s position — when you have a vaccine being
developed with public funding and you give the rights to one firm, you have
every right to put in place conditions to make sure vaccine will be
available to all who need it,” he said.

“The U.S. government has to at least justify why an exclusive license is
necessary,” WIlson added.

Sanofi could be the best company for the job

The company has experience with vaccines against viruses in the same family
as Zika, known as flaviviruses, having developed vaccines for Japanese
encephalitis and dengue fever.

This could explain why the U.S. Army is keen to entrust the Zika virus
vaccine to Sanofi, which is an established player and one with a track
record of supplying vaccines to developing countries, according to Wilson.

“It is still more or less true that only the big multinational
pharmaceutical companies have ever been able to successfully bring a truly
new vaccine to market. Even when you have a vaccine candidate that’s at the
stage of this Zika one is now, there are still many challenges involved in
the later stages of development,” he said.

However, the capacity of pharmaceutical firms in India, Brazil and China to
develop vaccines is “growing rapidly” and some of these firms could
probably bring the vaccine to market, although perhaps not as rapidly as a
multinational, WIlson said.

The vaccine industry has long been dominated by four major multinational
pharmaceutical companies — GlaxoSmithKline, Merck, Sanofi-Pasteur, and
Pfizer, which accounted for approximately 86 percent of global vaccine
revenue in 2015. Their monopoly is attributed to entry barriers such as
high start-up costs and long lead times; vaccines can take anywhere from 10
to 16 years to reach the market, preventing other companies from competing.

Phase III trials are technically difficult to conduct and many drugs and
vaccines fail them, and developing a robust manufacturing process is “very
technical” and is subject to “stringent regulatory requirements,” which can
be hard to navigate, Wilson explained.

“The U.S. Army may want a MNC partner because they believe that is the
surest way to ensure that the vaccine gets developed quickly. There are
only a few companies out there that have the relevant experience and have
shown an active interest in developing country markets, which Sanofi has
demonstrated,” he said.

Access will not be an issue in the poorest countries if GAVI steps in

In relation to MSF’s and KEI’s concerns about access to the vaccine, if
approved, GAVI, the Vaccine Alliance — a partnership of major donors and
pharmaceutical companies designed to ensure access to vaccines for children
in developing countries — could support low-income countries in purchasing
the vaccine, Wilson said.

Sanofi confirmed in an email to Devex that it has worked with GAVI on
distribution of vaccines in the past, and so working with the alliance on
the Zika vaccine was “certainly a possibility,” but that a strategy for
“pricing and distribution” would be developed later in the process.

However, the real problem of access will be in middle-income countries,
such as Brazil, which are ineligible for GAVI funding but where the vaccine
is urgently needed.

“Sanofi doesn’t see a market in the poorest countries and so they’re happy
to provide vaccines at a reasonable price there through GAVI, since it
would be seen as bad PR not to. But they are not necessarily prepared to
make those concessions in places like Brazil and India, where the greatest
access concerns would be,” Wilson said.

Sanofi has bad track record when it comes to serving developing countries,
MSF says

MSF spoke out against Sanofi in 2015 after the company decided to stop
manufacturing a pan-African snakebite antivenom because it was no longer
lucrative, leaving a gap in supplies that MSF said would be likely to lead
to unnecessary deaths.

The NGO is worried that if given the exclusive license for the Zika
vaccine, the pharmaceutical company will follow the same path and neglect
countries with great need but less opportunities for profit, according to
Judit Rius Sanjuan, MSF’s U.S. access campaign manager.

Instead, Sanjuan wants the U.S. Army to offer Sanofi a nonexclusive
license, which she argued would be “better public policy,” ensure the Zika
virus has broader geographical scope, and protects the U.S. government from
“having all its apples in one basket.”

There are other ways to get medicines through development and into markets

There have been successful examples of the U.S. government offering
nonexclusive licenses for patented technologies through the United Nations
backed Medicines Patent Pool, a global health financing mechanism set up in
2010 to share drug technology and research to speed up development, lower
costs and increase access to newer HIV/AIDS, viral hepatitis C, and
tuberculosis treatments in developing countries.

MPP works by signing agreements with patent holders — such as the NIH and
the U.S. Army but also nonprofits, pharmaceutical companies and individuals
— to create a pool of relevant patents. The partners are then licensed to
generic drug manufacturers who can then produce generic versions of the
medicines, often utilizing more than one patented technology in the process
of development.

For example, in 2010, the NIH licensed a patent on Darunavir to the MPP,
which spurred the development of a new combination drug. Furthermore, Johns
Hopkins University announced on Jan. 25 that it is licensing its patent for
the drug candidate sutezolid, which could be used to treat tuberculosis,
exclusively to the MPP.

While the MPP does not currently work on vaccines, and so licensing to the
MPP was not an option for the U.S. Army, these examples set a “good
precedent” for “innovative” nonexclusive licensing agreements and how
effectively sharing research can expedite research and development,
increase collaboration, and diversify the medicine development process,
MSF’s Sanjuan said.

Furthermore, there have been other notable examples of the U.S. granting
nonexclusive licenses for the development of vaccines. For example, the
human-bovine rotavirus vaccine technology was licensed by the NIH to eight
organizations, one in the United States and seven in the developing
countries, to manufacture and distribute the rotavirus vaccine.

Zack Struver, Communications and Research Associate
Knowledge Ecology International
zack.struver at keionline.org
Twitter: @zstruver <https://twitter.com/zstruver>
Office: +1 (202) 332-2670 Cell: +1 (914) 582-1428

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