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

Jamie Love james.love at keionline.org
Sat Jan 28 08:43:28 PST 2017

According to GAVI, these are the countries eligible for GAVI subsidies:

Practically none are in the Western Hemisphere.

This is the cost to the US taxpayers


Paul's point that GAVI will help poor countries implies the Army will give
Sanofi a monopoly, and then ask the US and other governments to tax
citizens to pay
​ ​
Sanofi subsidies to make the vaccine cheaper to people in the GAVI eligible
countries.   Sounds like a good plan.  For Sanofi.
​  Not for the taxpayers. ​

Here is the FDA approval letter, from 2009, to the small firm that
registered a vaccine for the Japanese Encephalitis Virus, Vaccine, which,
according to the NIH,
​ ​
uses the same platform as the ZKIP vaccine.

Below is a link to and some text from the November 7, 2016 NIH press
release on the first 5 clinical trials the US taxpayers are funding on the
Zika vaccine. And this
​ ​
is just the beginning, if the trial results are good.

Note the press release mentions the fact that "BARDA is funding the
advanced development of the ZPIV vaccine candidate through a six-year
contract with Sanofi Pasteur, which established a collaborative research
and development agreement with WRAIR to accelerate further development of
the vaccine."

If the Army is doing the trials itself, even using military personnel as
subjects, funding Sanofi's development work on the vaccine for SIX YEARS, I
don't see how a worldwide life
patent exclusive license to Sanofi is legal under 35 USC 209, unless the
​thinks the statute is not binding.

But really, how crazy is it for the US taxpayers to invent and pay for the
development, and then have to negotiate with a French company to get the
vaccine if it works?   Negotiate a price to avoid having children born with
brain damage and small heads?  (Value based pricing experts, what is that
worth these days?)

You can't just let the NIH or the Army, and Sanofi, wave their hands and
claim an exclusive license (life of patent, worldwide) is actually
"necessary" (the statutory standard), without more transparency and
evidence than what we have now.  The reason the Army wants to avoid a
hearing (and why the NIH never gives them either), is because the facts, if
every made public, don't favor the use of an exclusive license.




"First of five planned clinical trials to test ZPIV vaccine."

WRAIR, NIAID and the Biomedical Advanced Research and Development Authority
(BARDA) part of the HHS Office of the Assistant Secretary for Preparedness
and Response (ASPR) have established a joint Research Collaboration
Agreement to support the development of this vaccine.

Led by WRAIR principal investigator Maj. Leyi Lin, M.D., the new study aims
to enroll 75 people ages 18 to 49 years with no prior flavivirus infection.
Flaviviruses include Zika virus, yellow fever virus, dengue virus, Japanese
encephalitis virus and West Nile virus. Participants will be randomly
divided into three groups: the first group (25 participants) will receive
two intramuscular injections of the ZPIV test vaccine or a placebo (saline)
28 days apart; the other two groups (25 participants each) will receive a
two-dose regimen of a Japanese encephalitis virus vaccine or one dose of a
yellow fever vaccine before beginning the two-dose ZPIV vaccine regimen.
Investigators chose to administer additional flavivirus vaccines because
U.S. service members are often vaccinated against these diseases before
deploying to Zika-endemic areas.

Additionally, a subgroup of 30 of the participants who receive the two-dose
ZPIV regimen will receive a third dose one year later. All participants in
the trial will receive the same ZPIV dose at each injection (5 micrograms).
A DoD Research Monitor, an independent physician not associated with the
protocol, will monitor the conduct of the trial and report any safety
issues to the WRAIR Institutional Review Board. Another independent group,
the Safety Monitoring Committee, will also monitor participant safety,
review data and report any issues to NIAID. As the regulatory sponsor,
NIAID ensures the trial follows the study protocol and informs the FDA of
any significant adverse events or risks. NIAID also maintains the
Investigational New Drug (IND) application(link is external) for the
candidate vaccine. The WRAIR study is expected to be completed by fall 2018.

Four additional Phase 1 studies to evaluate the ZPIV investigational
vaccine are expected to launch in the coming months. These include

A trial enrolling 90 adults ages 18-49 years at the Center for Vaccine
Development at the Saint Louis University School of Medicine. This site is
an NIAID-funded Vaccine and Treatment Evaluation Unit, and Sarah George,
M.D., will serve as principal investigator. All participants will receive
either two injections of ZPIV or a placebo 28 days apart. Participants will
be randomly assigned to receive either a high, moderate or low dose at both
injections to evaluate the optimal dose for use in larger future studies.
A trial enrolling 90 adults ages 21-49 years at the clinical research
center CAIMED, part of Ponce Health Sciences University in Puerto Rico. The
site is supported by NIAID via a subcontract from the Saint Louis
University School of Medicine. This trial will examine the vaccine’s safety
and immunogenicity in participants who have already been naturally exposed
to dengue virus. Participants will be randomly assigned to receive either a
high dose, moderate dose or a placebo. Elizabeth A. Barranco, M.D., will
lead the trial.
NIAID’s Vaccine Research Center (VRC) will test the ZPIV vaccine candidate
as a boost vaccination to its DNA Zika vaccine candidate, which entered
Phase 1 clinical trials in August. The next part of the study, which will
enroll 60 additional participants ages 18-50 years, will take place at the
NIH Clinical Center in Bethesda, Maryland, the Center for Vaccine
Development at the University of Maryland School of Medicine’s Institute
for Global Health in Baltimore, and Emory University in Atlanta. Half of
the participants will receive the NIAID Zika virus investigational DNA
vaccine followed by a ZPIV vaccine boost four or 12 weeks later. The
remaining participants will receive only two doses of ZPIV vaccine four or
12 weeks apart. Julie Ledgerwood, D.O., chief of the VRC’s clinical trials
program, will serve as principal investigator.
A WRAIR-funded trial enrolling 48 adults ages 18-50 years will be conducted
at the Center for Virology and Vaccine Research, part of Beth Israel
Deaconess Medical Center and Harvard Medical School in Boston. One group of
participants will receive a single dose of the ZPIV vaccine and all other
participants will receive two doses of the ZPIV vaccine at varying
intervals. Kathryn Stephenson, M.D., M.P.H., of Beth Israel Deaconess
Medical Center, will lead the trial.

BARDA is funding the advanced development of the ZPIV vaccine candidate
through a six-year contract with Sanofi Pasteur, which established a
collaborative research and development agreement with WRAIR to accelerate
further development of the vaccine.

NIAID conducts and supports research—at NIH, throughout the United States,
and worldwide—to study the causes of infectious and immune-mediated
diseases, and to develop better means of preventing, diagnosing and
treating these illnesses. News releases, fact sheets and other
NIAID-related materials are available on the NIAID website.


On Fri, Jan 27, 2017 at 11:29 PM, Wilson, Paul A. <pw2101 at cumc.columbia.edu>
> Hi Jamie,
> I wish I could say otherwise, but I know nothing more about the deal than
was in the papers, so in speaking to the reporter I was just trying to
provide general background. I pointed out to her that Sanofi’s claim to be
bearing future costs and risks was undercut if they were getting funding
for the trials, as the earlier announcements implied. Another thing that I
don’t understand is what happened to the earlier announcement of a
collaboration involving Fiocruz. Do you know what happened to this?
> I didn’t say that only a few big companies can make and distribute
vaccines, but that until now they had been responsible in almost all cases
for bringing truly new vaccines through the later phases of development.
There are some exceptions (such as the Chinese Hep E vaccine) and will
surely be more soon. I don’t have a good sense of how difficult this
vaccine will be to bring through trials and regulatory approval, as I don’t
know anything about the technology involved, although it doesn’t sound
particularly new-fangled.
> Another consideration that the army might have had is that no firm based
in a developing country has yet gotten FDA approval for a vaccine, or at
least that was the case when I last checked a while back. Is that still
true to your knowledge? Presumably this is an important ambition of Serum
and perhaps others.
> I (and the article) made very clear that Gavi provides no protection for
people in industrialized countries, or even for people in most developing
countries, as the vast majority now live in countries that aren’t eligible
for Gavi support. That’s why any provisions on access and affordability are
so important in deals like this.
> Paul
> From: Jamie Love <jamespackardlove at gmail.com> on behalf of Jamie Love <
james.love at keionline.org>
> Date: Friday, January 27, 2017 at 12:44 PM
> To: Zack Struver <zack.struver at keionline.org>, Paul Wilson <
pw2101 at columbia.edu>
> Cc: Ip-health <ip-health at lists.keionline.org>
> Subject: Re: [Ip-health] Devex: Zika vaccine could be delayed,
unaffordable after US Army grants exclusive rights to pharma company
> Interesting to hear Paul Wilson's opinions.  Does he know much money
Sanofi has promised to invest?
> Sanofi
> told Statnews they expected the US government to pay for the late stage
> .  Was Sanofi lying then, or now?
>  Sanofi certainly is not paying for the current trials
> .  The Army won't say anything about who will be paying for the future
trials, although the NIH is putting out press releases about the six year
funding agreement with Sanofi.
> T
> he 2009 vaccine for Japanese encephalitis that used the same platform as
> wasn't developed a big pharma company, I believe it was registered by I
> ntercell AG
> , a firm few have heard of.
> The notion that only a few big companies can make and distribute vaccines
is false.
> And in any case, Sanofi has already been given $43 million to work on
this, without a license.
> The notion that GAVI is going to protect people in developing countries
from price gouging from Sanofi would be more compelling if Sanofi was not
given exclusive rights.   Why give a company a monopoly and then have a
discussion about the price?   And, what about US residents who want to
avoid having babies with small heads and brain damage?  If GAVI going to
help them?  No.
>  Jamie
> On Fri, Jan 27, 2017 at 5:47 PM, Zack Struver <zack.struver at keionline.org>
>> Zika vaccine could be delayed, unaffordable after US Army grants
>> rights to pharma company
>> By Sophie Edwards | 27 January 2017
>> The U.S. Army’s plan to grant exclusive rights to a promising Zika
>> to a major pharmaceutical company has raised questions about whether that
>> threatens its future affordability and availability to people in
>> countries.
>> 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
>> 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
>> children.
>> The deal was posted by the Army on the public Federal Register in
>> 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
>> company an exclusive right to make, use and sell the vaccine for 20
>> as well as 12 years of marketing and data exclusivity even after the
>> 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
>> to stop developing the vaccine if it decides it is commercially
>> unattractive.
>> MSF wants the U.S. Army to consider granting an “open nonexclusive”
>> 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
>> 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
>> to address the lack of access to medicines in many developing countries,
>> appears to agree with MSF’s recommendations. In its 2016 report, the
>> 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
>> and most safely provide this potential vaccine for public use to combat
>> 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
>> to allow time to compose written responses to the submissions.
>> Experts have predicted the Zika market could be worth more than $1
>> 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
>> technology for Zika known as SAM (self-amplifying mRNA), and Japanese
>> company Takeda has also entered the vaccine hunt with $312 million
>> 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
>> 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
>> funds.
>> “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
>> 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
>> 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
>> transferable and have been sold to other companies for upwards of $300
>> million.
>> However, the statement from the U.S. Army said there was a strong case
>> granting Sanofi exclusive rights to the technology, due to competition
>> the “many” groups working on a Zika vaccine. Sanofi is taking on “risk”
>> accruing the license since there is a “long way to go in terms of time
>> 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”
>> Sanofi.
>> “The federal government needs a non-federal partner with the research and
>> production capabilities and the willingness to invest their own
>> 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
>> 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
>> be transparent about the costs of research and development.
>> The U.S. Army responded by saying the license agreement has stipulations
>> 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
>> due to the fact Zika is “still a moving target” and there is “no clear
>> 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.
>> 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
>> 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
>> people become immune.
>> If this turns out to be the case, however, MSF’s and KEI’s concerns may
>> 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
>> 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
>> 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
>> “It is still more or less true that only the big multinational
>> pharmaceutical companies have ever been able to successfully bring a
>> new vaccine to market. Even when you have a vaccine candidate that’s at
>> stage of this Zika one is now, there are still many challenges involved
>> the later stages of development,” he said.
>> However, the capacity of pharmaceutical firms in India, Brazil and China
>> develop vaccines is “growing rapidly” and some of these firms could
>> probably bring the vaccine to market, although perhaps not as rapidly as
>> 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
>> to 16 years to reach the market, preventing other companies from
>> Phase III trials are technically difficult to conduct and many drugs and
>> vaccines fail them, and developing a robust manufacturing process is
>> technical” and is subject to “stringent regulatory requirements,” which
>> 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
>> in developing countries — could support low-income countries in
>> 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
>> is urgently needed.
>> “Sanofi doesn’t see a market in the poorest countries and so they’re
>> 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
>> access concerns would be,” Wilson said.
>> Sanofi has bad track record when it comes to serving developing
>> 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
>> 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
>> virus has broader geographical scope, and protects the U.S. government
>> “having all its apples in one basket.”
>> There are other ways to get medicines through development and into
>> There have been successful examples of the U.S. government offering
>> nonexclusive licenses for patented technologies through the United
>> backed Medicines Patent Pool, a global health financing mechanism set up
>> 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
>> — 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
>> 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,
>> Hopkins University announced on Jan. 25 that it is licensing its patent
>> 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
>> 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
>> 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
>> keionline.org
>> _______________________________________________
>> Ip-health mailing list
>> Ip-health at lists.keionline.org
>> http://lists.keionline.org/mailman/listinfo/ip-health_lists.keionline.org
> --
> James Love.  Knowledge Ecology International
> http://www.keionline.org/donate.html
> KEI DC tel: +1.202.332.2670, US Mobile: +1.202.361.3040, Geneva Mobile:
+41.76.413.6584, twitter.com/jamie_love

James Love.  Knowledge Ecology International
KEI DC tel: +1.202.332.2670, US Mobile: +1.202.361.3040, Geneva Mobile:
+41.76.413.6584, twitter.com/jamie_love

More information about the Ip-health mailing list