WASHINGTON, May 20, 2020 /PRNewswire/ -- Vanda
Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today released a letter
(below) from Mihael H.
Polymeropoulos, M.D., President and CEO of Vanda
Pharmaceuticals, proposing an approach to Clinical Trial Data
Sharing in order to facilitate discovery and clinical utility of
COVID-19 therapeutics. Vanda is also involved in the development of
therapeutic solutions for COVID-19 and currently in Phase III
studies with tradipitant for the treatment of Acute Respiratory
Distress Syndrome (ARDS) associated with COVID-19.
Clinical Trial Data Sharing, COVID-19 and
Remdesivir
Mihael H. Polymeropoulos,
M.D.
The COVID-19 pandemic has created an urgent need for scientific
solutions to this deadly virus. The pandemic surprised the
world with a new strain of coronavirus never encountered before,
which, like its predecessor, has the capacity to infect humans with
severe and deadly consequences. While this pandemic has
stunned the world's populations, we are more prepared than ever to
respond with a rich scientific armamentarium of tools that can be
deployed in the war against this new virus resulting from the
extraordinary advances in medical discoveries and treatments in the
twenty years since the first full sequencing of the human
genome.
While the reaction to the 1918 world epidemic was mostly one of
quarantine and restrictions in movement, the world today can do
better. In 1918, the world did not know the identity of the
organism that was killing so many, nor did it know what a virus
was, as viruses had not yet been discovered. Now equipped
with the knowledge of over a century of research and tremendous
advances in science and therapeutics, we stand in front of this
challenge well equipped and ready to respond. In many ways,
our response has been similar to the 1918 epidemic, with mitigation
measures that include closing of public places and reducing
opportunities for contact, while monitoring the curves of new cases
and mortality rates. Vaccines and therapeutics are on the
drawing board but how and when they may be of value is
uncertain. The urgency and mobilization of the scientific
community across the globe is impressive. The collective
scientific understanding of the workings of the virus, the clinical
course of the infection and the therapeutic approaches are mounting
on a daily basis.
Although this is great news, the pandemic has imposed an
extremely demanding pace on the timetable for the pursuit of
scientific answers and solutions. The ability of developing
therapeutic solutions does not just depend on the availability of
research tools and ideas. The ideas must leverage scientific
tools and then they must be tested. Testing of potential
therapeutics happens in human volunteers that have been infected
with the COVID-19 virus. One of these programs is the
development of antivirals that are intended to slow down or block
replication of the virus.
The U.S. National Institute for Allergy and Infectious Diseases
(NIAID) and Gilead Sciences brought forward the testing of one of
these antivirals, remdesivir, a nucleoside analog that induces
errors in the copying machinery of the virus, thereby slowing down
replication. Remdesivir has been recently studied in two
types of programs, a placebo-controlled study and an open label
program. The NIAID remdesivir placebo-controlled study was
concluded and topline results were reported on April 29, 2020. The topline results were
communicated during a brief meeting at the White House by the
Director of NIAID and advisor to the President, Dr. Anthony Fauci. The communication was
verbal, short, and conveyed that the study had shown that
remdesivir reduced hospital stay by 4 days for remdesivir treated
patients as compared to placebo, but it did not significantly
reduce mortality. No other data were presented in any other
scientific or media forum. Dr. Fauci acknowledged that his
preference would have been to present this data at a scientific
meeting but that the situation required a more immediate
communication and that the data would be submitted for a peer
review publication in the near future. Two days later, the
U.S. Food and Drug Administration (FDA) issued an Emergency Use
Authorization (EUA) approval of remdesivir in treating patients
with severe COVID-19 infection.1 The prescribing
information presented by the FDA included the same summary
information that was reported at the White House two days earlier,
but no additional information on the efficacy trial was
given.2 Similarly, the FDA in its cover letter
suggested that it had reviewed the topline data and based on that
deemed it appropriate to issue an EUA.
The paucity of information around this critical therapeutic
development for COVID-19 is troubling. The NIH, the FDA and
Gilead Sciences could simply provide the raw data from the clinical
trials to the public immediately. Such a concept of sharing
of clinical trial data is not new, instead, it is highly encouraged
by the scientific community and data sharing disclosures are now
required by most scientific journals according to the
recommendations of the International Committee of Medical Journal
Editors.3 The reason for sharing of clinical data
includes allowing the scientific community to independently form
their own conclusions from their own analyses, develop new insights
from the data, and accelerate discoveries in the field by not
having to repeat the same experiments. In the case of
remdesivir and COVID-19, this degree of data sharing is even more
urgent given the finite amount of time within which a study can be
conducted in the face of a declining number of new cases.
There are a number of questions that could be answered by the
existing remdesivir NIAID study that remain unanswered by the
complete unavailability of the data. For example: Is there a
subgroup of patients that performed better than others? Is this
subgroup of a certain characteristic, such as age, sex, race,
genetic makeup, time since infection, severity of disease, viral
load, medication, underlying condition? And there are many
others to be answered.
The FDA has authorized remdesivir for all people with severe
COVID-19 infection, but there may not be enough supply for all
eligible patients at this time. How are doctors supposed to
choose who should receive it? The prevailing rationale, which
would suggest that it be administered to the most severely ill
first, may be misguided and not supported by the data. What
if analysis of the existing data showed that remdesivir works
better when given to less severe patients or very early after the
infection? In this example, providing the currently limited
supply of remdesivir to severe patients may be wasteful and may
deprive patients who could benefit from it instead. Another
reason for sharing the raw data is that there is no other large
dataset of patients with COVID-19 infection and thus there is not a
good guide how to optimally design any therapeutic programs.
The question of whether viral load is associated with response is
also of critical importance. Imagine a scenario where the
drug's effect was dependent not on disease severity but rather on
viral load, so that severely ill patients with low viral load
respond to the drug, but severely ill patients with high viral load
do not. What if some patients have zero viral load but
nonetheless have a severe infection, would they be candidates for
treatment? Even in a more complex scenario, what if patients
had no decrease in viral load but the infectivity of the virus post
remdesivir treatment was decreased? What is the cause of mortality
and how does it differ between remdesivir and placebo?
Unfortunately, so far there has been little to no discussion
about data transparency and data availability for remdesivir.
Dr. Fauci's statement that the results will be submitted for peer
review is not enough. On the face of it, it appears that this
is consistent with the well-established approach to validate
scientific findings. During this process, a scientific report
is submitted to a journal and the editorial board appoints two or
more reviewers to independently critique the paper and advise
whether the conclusions are supported by the data presented.
This process is well-intentioned, and has served us well, but in
and of itself it is grossly inadequate for the task in hand.
The American public is comforted that expert scientists opine on
the validity of a potential treatment but they would likely prefer
that the data are also fully and transparently available to the
public for inspection and analysis for both verifying and
learning.
Reliance upon just the ordinary peer review of scientific
reports is not sufficient in this case. Dr. Fauci's
suggestion that worries about "leaks" or "ethical concerns"
prompted this style of announcement is not an acceptable
explanation either. Most of the American public is not
concerned with the reasons that compelled the verbal announcement
of the results from a White House office on April 29. The
American public is interested in seeing the data and having the
data available for all to examine and learn from. The speed
of the FDA decision in issuing an EUA for remdesivir needs to be
commended but the absence of any available detailed information is
of great concern. The EUA was granted based on the
information presented to the FDA. The data which the FDA used
to make its decision must become immediately available to the
public. If the FDA deems that it needs more information to
grant a full approval, it can request this information in due
course. Until then, the FDA should provide to the public the
information that the FDA scientists used to make its decision.
If the NIAID, the FDA and Gilead Sciences decided to follow this
recommendation and share the data, could they do it quickly?
The process that the NIAID scientists used to analyze the available
data is as follows: anonymized patient data are collected
throughout the study, they are tabulated as raw data, and then
certain parameters are derived. These data are stored in
standard format files which are of two types, the RAW and the
DERIVED data files. These exact files that the NIAID analyzed
and which Gilead Sciences filed with the FDA, can be shared with
minimal effort and within minutes after the leaders of the NIAID,
the FDA and Gilead Sciences decide to share. In summary,
there is no technical hurdle for the immediate release of the
underlying remdesivir clinical study data. Concerns about
credit and intellectual property can easily and expediently be
addressed without imposing any delay on the release of this
data.
We are experiencing a historic health crisis where success is
dependent on a community coming together and overcoming a
tremendous challenge to humanity. Open source sharing of
information has always accelerated solutions to problems, and I am
confident that it will work here as well. In the scientific
community, open source mentality and data sharing has served
humanity well, especially recently with the Human Genome project,
where genetic data were made immediately available to the
scientific community for the betterment of human health. This
is the time to show that pharmaceutical companies and government
agencies put patients first. If indeed the interest of
patients is front and center, which it should be, then the NIAID,
Gilead Sciences and the FDA will release ALL data from the
remdesivir studies without delay.
More than ever, the American public is dependent on the
competencies of its leaders, in the government and science
alike. Trust in the system is conditional and temporary and
is based upon transparency and truthfulness. The American
public will not, and should not, blindly trust the expert.
The American public should not have to wait for a handful of
scientists, no matter how brilliant, to review the information and
give their approval. The American public is entitled to
unconditional access to all such data so that all people, and not
just a few, can judge the course of affairs and make
decisions. In the midst of this difficult moment for
humanity, an unconditional data sharing movement may become a
silver lining and the rainbow promise past the storm. The
American public, scientists, and non-scientists, bonded by sharing
and trust, will overcome this new challenge. Let us remove from the
vocabulary of our democracy the "trust me I am an expert" mentality
and replace it with "transparency for all."
References
- Hinton D. U.S. Food and Drug Administration letter to Gilead
Sciences, Emergency Use Authorization for remdesivir. White Oak, Md.: U.S. Food and Drug
Administration, May 2020.
https://www.fda.gov/media/137564/download.
- Fact Sheet for Patients And Parents/Caregivers, Emergency Use
Authorization (EUA) of Remdesivir For Coronavirus Disease 2019
(COVID-19). White Oak, Md: U.S.
Food and Drug Administration (FDA), May
2020. https://www.fda.gov/media/137565/download.
- Taichman DB, Backus J, Baethge C, et al. Sharing clinical trial
data: a proposal from the International Committee of Medical
Journal Editors. Ann Intern Med 2016;164:505-6.
About Vanda Pharmaceuticals Inc.
Vanda is a leading global biopharmaceutical company focused on
the development and commercialization of innovative therapies to
address high unmet medical needs and improve the lives of patients.
For more on Vanda Pharmaceuticals Inc., please visit
www.vandapharma.com and follow us on Vanda's Twitter and
LinkedIn.
Corporate Contact:
AJ Jones II
Chief Corporate Affairs and Communications Officer
Vanda Pharmaceuticals Inc.
202-734-3400
pr@vandapharma.com
Elizabeth Van Every
Head of Corporate Affairs
Vanda Pharmaceuticals Inc.
202-734-3400
pr@vandapharma.com
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SOURCE Vanda Pharmaceuticals Inc.