Experimental therapy might help people with serious COVID-19 complications
Albert Einstein College of Medicine
April 3, 2020–(BRONX, NY)– Montefiore Health System and Albert Einstein College of Medicine has joined a clinical trial to evaluate the experimental drug remdesivir to treat people who are hospitalized with severe COVID-19 infection. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is sponsoring the trial. This treatment has the potential to help people who have serious lung complications as a result of COVID-19. Recruitment for the trial began in March and is still underway.
Montefiore-Einstein is one of 46 testing sites nationwide and is the first site in New York State to open. NIAID launched the multi-center international effort to determine if remdesivir, a broad-spectrum antiviral drug, acts against COVID-19 viral infection. Remdesivir has shown promise in animal models of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), both caused by human coronaviruses.
The randomized, double-blind, placebo-controlled trial is being led by principal investigator Barry Zingman, M.D., professor of medicine at Einstein and clinical director, infectious diseases, in the Moses division of Montefiore Health System. The trial is “adaptive,” meaning it can be modified to include other investigational treatments. “This flexibility allows us to add additional therapies to the trial step-by-step to improve treatment as the pandemic continues,” said Dr. Zingman.
Trial participants are hospitalized patients with a laboratory-confirmed coronavirus infection and lung complications, including rattling sounds when breathing, a need for supplemental oxygen, abnormal chest X-rays showing pneumonia, or the need for a mechanical ventilator.
People in the treatment group will receive 200 mg of remdesivir intravenously on the first day of their enrollment in the study and will receive another 100 mg each day for the duration of hospitalization, for up to 10 days total. The placebo group will receive an equal volume of a solution that resembles remdesivir but contains inactive ingredients.
Montefiore and Einstein’s robust clinical trial infrastructure contributed to its selection and rapid approval for participation. No therapies have yet been approved by the U.S. Food and Drug Administration for treating COVID-19.
Remdesivir, an investigational antiviral therapy, was developed by Gilead Sciences, Inc.
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About Montefiore Health System
Montefiore Health System is one of New York’s premier academic health systems and is a recognized leader in providing exceptional quality and personalized, accountable care to approximately three million people in communities across the Bronx, Westchester and the Hudson Valley. It is comprised of 11 hospitals, including the Children’s Hospital at Montefiore, Burke Rehabilitation Hospital and more than 200 outpatient ambulatory care sites. The advanced clinical and translational research at its medical school, Albert Einstein College of Medicine, directly informs patient care and improves outcomes. From the Montefiore-Einstein Centers of Excellence in cancer, cardiology and vascular care, pediatrics, and transplantation, to its preeminent school-based health program, Montefiore is a fully integrated healthcare delivery system providing coordinated, comprehensive care to patients and their families. For more information please visit http://www.montefiore.org. Follow us on Twitter and view us on Facebook and YouTube.
About Albert Einstein College of Medicine
Albert Einstein College of Medicine is one of the nation’s premier centers for research, medical education and clinical investigation. During the 2019-20 academic year, Einstein is home to 724 M.D. students, 158 Ph.D. students, 106 students in the combined M.D./Ph.D. program, and 265 postdoctoral research fellows. The College of Medicine has more than 1,800 full-time faculty members located on the main campus and at its clinical affiliates. In 2019, Einstein received more than $178 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States through Montefiore and an affiliation network involving hospitals and medical centers in the Bronx, Brooklyn and on Long Island. For more information, please visit http://www.einstein.yu.edu, read our blog, follow us on Twitter, like us on Facebook, and view us on YouTube.
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Some news on remdesivir availability and production lead times, as well as how many does currently exist.
It turns out that previously, there were a total of about 140,000 courses of treatment worth in inventory, all of which has been committed to be used in clinical trials at no cost to the people getting it.
Also, a report in seeking alpha asserts that end to end production time for manufacturing the drug was previously one year, but Gilead expects to shorten this to six months.
So…it takes between one year to make any of it at all.
Gilead hopes to make enough for 500,000 treatment courses by October, and another 500,000 by year end.
What this all ads up to is, it appears that this drug will be in limited supply, even if it turns out to work miraculously well.
And if it turns out to be approved for usage in the immediate future, there will likely not be enough if it to go around for everyone in the world who needs and would like to have it.
So that sounds like a very substantial problem: Who will get some, and who will decide, and how will they decide it? It seems that first come first serve would be about the only fair way, to my way of thinking.
https://seekingalpha.com/news/3558442-gilead-ramps-up-remdesivir-production-ahead-of-approvals
Confirmation of these assertions is required…I am just reporting what I have found published.
A recent article in Forbes contains a lot of info on the malaria drugs, including some worrisome findings, prior to this disease outbreak, of substantial percentages of death in mice that were given hydroxychloroquine and metformin, which is a common drug taken by people with diabetes.
““To our utter surprise, both HCQ and CQ when combined with metformin resulted in a surprising death rate in 30-40% of mice. In contrast there were no deaths in the single treatment groups,” said the authors.”
This result is a surprise to researchers, but that these drugs are far less safe for some subset of people is no surprise…this is just one more area of concern regarding these drugs.
https://www.forbes.com/sites/victoriaforster/2020/04/05/researchers-warn-that-covid-19-treatment-touted-by-trump-may-be-toxic-when-combined-with-diabetes-drug/#4a7f56355f82
Again, these results are not the last word on anything…mice are not little people, however…it must be looked at very carefully, and handing these drugs out to sick people needs to be done cautiously to avoid making some people worse off than if they received standard of care, or some other treatment.
Typo in forst sentence above.
It should say:
“Some news on remdesivir availability and production lead times, as well as how many doses currently exist.”
Assuming the drug works. How many trial patients might die who end up being given the placebo?
Should we just assume that all drugs that might have some value are safe and 100% effective?
What is the basis for the justification of making such an assumption?
Are there any examples of drugs that turned out to be less effective than people were hoping?
Any examples of experimental drugs that were more dangerous than anyone knew prior to testing them scientifically?
Anyone interested in this drug ought to read this letter from the CEO of Gilead:
“Daniel O’Day – April 04, 2020
Over the course of the past week, Gilead has been working in consultation with regulatory authorities to establish additional expanded access programs for remdesivir, our investigational medicine for COVID-19. The programs enable hospitals or physicians to apply for emergency use of remdesivir for multiple severely ill patients at a time. These are patients who cannot take part in clinical trials and where the word “emergency” is all too real for them, their families and the healthcare providers advocating on their behalf.
We know the desperate urgency of reaching these patients and believe that the expanded access program will help to accelerate the process. New U.S. sites have been initiated and we are adding more on an ongoing basis. We are also making progress in Europe. Yesterday, the European Medicines Agency announced that it has provided EU member states with recommendations on implementing expanded access programs for remdesivir in their countries.
In addition to the expanded access programs, we continue to provide remdesivir on an individual compassionate use basis for children and pregnant women. More than 1,700 patients have now been treated through these programs.
Remdesivir is still an investigational medicine and has not been approved by regulatory authorities anywhere in the world. The safety and efficacy are not yet known so while we feel the greatest sense of urgency in our work with remdesivir, we must take the responsible, ethical approach of determining whether it is indeed a safe, effective treatment. This is why multiple clinical trials for remdesivir are underway, involving thousands of patients with COVID-19 across the world.
We know from the heartbreaking letters we receive, the images we see in the news and the all-too-bleak statistics that the urgency to find broad, effective solutions becomes more intense each day. In the ways we believe it is appropriate for Gilead to play a role today – primarily through clinical trials, as well as expanded access and compassionate use – we are doing everything it takes to meet our significant responsibility with remdesivir.
Supply and Donation of Remdesivir
A critical part of Gilead’s responsibility today is ensuring sufficient supply of remdesivir. To provide product for trials, compassionate use and expanded access, we needed to effectively start from ground zero in ramping up our supplies. The progress we have made on this to date is thanks to the actions we have been taking since January to rapidly expand production and increase supply.
As soon as we knew that remdesivir may have potential in treating the novel coronavirus, our teams began to establish a supply chain for large-scale production. Then, as now, there were many unknowns including how long the outbreak would last, at what scale and whether remdesivir is a safe and effective treatment for COVID-19. We made the decision to invest and scale up regardless, because if remdesivir was going to be needed for patients, we had to be ready.
We knew there would be challenges in producing the amounts we would ideally want to deliver in a short timeframe. One of these challenges is the length of time it takes to produce remdesivir. It is a linear process that requires specialized chemistry and multiple chemical reactions, some of which can take several weeks to complete. It also calls for scarce raw materials as well as sterile manufacturing capabilities with limited global capacity, which are needed to make finished vials ready for administration to patients.
Working within these parameters, our teams have found multiple ways of accelerating production. These include process improvements that cut production times. As a result, we have reduced the end-to-end manufacturing timeline from approximately one year, to around six months. We have repurposed some of our own facilities to focus on remdesivir and we have also increased our network of external manufacturing partners around the world.
In the space of two months, we have significantly increased our available supply of remdesivir using the inventory of active pharmaceutical ingredients we already had on hand. Our existing supply, including finished product ready for distribution as well as investigational medicine in the final stages of production, amounts to 1.5 million individual doses. Depending on the optimal duration of treatment, which is something we are studying in clinical trials, this supply could equate to well over 140,000 treatment courses for patients.
Our efforts to increase supply continue with a strong sense of urgency. There is a long way to go and a lot of work to be done but I’m pleased that, despite the challenges we have been able to get supply levels to where they are today in a very short space of time – through the resourcefulness of our teams, creative approaches and collaboration.
Gilead is providing the entirety of this existing supply at no cost, to treat patients with the most severe symptoms of COVID-19. The 1.5 million individual doses are available for compassionate use, expanded access and clinical trials and will be donated for broader distribution following any potential future regulatory authorizations. These doses are for treating patients with severe symptoms, through daily intravenous infusions in a hospital setting. Having a potential treatment in our hands comes with significant responsibility. Providing our existing supplies at no charge is the right thing to do, to facilitate access to patients as quickly as possible and in recognition of the public emergency posed by this pandemic.
Looking Forward
While we are working with the utmost sense of urgency on the immediate needs before us, we are also looking forward. Over the next weeks and months, we will be able to further increase our supplies of remdesivir as raw materials with long lead times become available for manufacture. We have set an ambitious goal of producing more than 500,000 treatment courses by October and more than 1 million treatment courses by the end of this year.
To help us meet and exceed this goal, we are building a geographically diverse consortium of pharmaceutical and chemical manufacturers to expand global capacity for raw materials and production. This collaboration will allow us to achieve far more than any of us could have done working alone. The international nature of the supply chain for remdesivir reminds us that it is essential for countries to work together to create enough supply for the world.
These are intense, ongoing efforts and while they continue, we must await the data from the clinical trials before we know whether remdesivir is a safe and effective treatment.
In the meantime, in the face of many unknowns and the exceptional circumstance of this pandemic, we are finding every means possible to meet our responsibilities with remdesivir today, and to be prepared for meeting the needs of patients in the future.”
https://www.gilead.com/stories/articles/an-update-on-covid-19-from-our-chairman-and-ceo
The simple stated bad news is…it takes 6 months to make even a single dose of remdesivir.
So it will be in limited supply for a long time, no matter what.
Interesting.
Why is it so? How is it made?
From their website: https://www.gilead.com/
Remdesivir for COVID-19; Manufacturing Process
Since January, Gilead has invested significant capital to establish a supply chain capable of large-scale production of remdesivir.
The production of remdesivir is a long, linear chemical synthesis process that must be completed sequentially and includes several specialized chemistry steps and novel substances with limited global availability. The process is both resource- and time-intensive, with some individual manufacturing steps taking weeks to complete. Because remdesivir is administered intravenously, production also requires sterile drug product manufacturing capabilities, which limits the number of organizations capable of manufacturing the medicine. This complex process impacts the ability to rapidly produce large quantities of drug supply in an emergency situation like the COVID-19 pandemic. In light of these realities, Gilead worked early on, before any clinical trials had started, to procure a steady flow of long-lead-time raw materials that will accelerate large-scale production of remdesivir by our current and future partners once these materials become available in significant quantities.
Over the last several weeks, we have also worked to shorten the manufacturing timeline through process improvements. The typical timeline for manufacturing a drug like remdesivir at scale is nine to 12 months; we have reduced that period to six to eight months. We continue to work on optimizing the chemical synthesis processes to further accelerate product deliveries and volumes.
Current and Projected Supply
As of January 2020, we were not actively manufacturing remdesivir. The manufacturing supply chain was scaled to periodically make small amounts of product for a compound in early development. We had inventory of finished product to treat just 5,000 patients.
Since then, we have proactively and rapidly scaled our supply chain. As of late March, using the active ingredient we already had in our inventory, we have increased our supply to more than 30,000 patient courses of remdesivir on hand, assuming a 10-day course of treatment for patients. As new raw materials arrive over the next few weeks from manufacturing partners around the world, our available supply will begin to rapidly increase.
Every day we are improving processes, shortening timelines and increasing volumes as we work to bring remdesivir to patients as soon as possible. Our goal is to produce a total of:
More than 140,000 treatment courses by the end of May 2020
More than 500,000 treatment courses by October 2020
More than 1 million treatment courses by December 2020
Several million treatment courses in 2021, if required
Is China a few weeks away from a resurgence of the virus?
https://www.msn.com/en-us/news/world/china-tourist-sites-packed-as-country-comes-out-of-coronavirus-lockdown/ar-BB12ddZV?ocid=msedgntp