Remdesivir - The Solution to the SARS-CoV-2 Virus?

Remdesivir is one of the frontline drugs being investigated as a solution to the COVID-19 pandemic.  Let's open the posting by looking at what Gilead, the manufacturer of the drug, has to say about remdesivir:

 

"Remdesivir is an investigational nucleotide analog with broad-spectrum antiviral activity – it is not approved anywhere globally for any use. Remdesivir has demonstrated in vitro and in vivo activity in animal models against the viral pathogens MERS and SARS, which are also coronaviruses and are structurally similar to COVID-19. The limited preclinical data on remdesivir in MERS and SARS indicate that remdesivir may have potential activity against COVID-19.

 

Remdesivir is an experimental medicine that does not have established safety or efficacy for the treatment of any condition.

 

Gilead’s response to COVID-19 entails three main areas:

 

1.) Remdesivir Clinical Trials

 

2.) Emergency Access to Remdesivir Outside of Clinical Trials

 

3.) Increasing Manufacturing and Supply for Remdesivir"

 

Remdesivir is a broad-spectrum antiviral pharmaceutical, developed by Gilead Sciences in 2009, which had been tested previously against RNA viruses including both the SARS and MERS coronavirus.  It was originally developed as a drug to combat hepatitis C (which it failed) and was repurposed as a potential treatment for both the Ebola and Marburg viruses.  

 

Remdesivir has undergone Phase 3 trials as a solution to the SARS-CoV-2 virus with the following results:

 

The full results of the study which was funded by the National Institute of Allergy and Infections Diseases (Anthony Fauci serves as the director of NIAID) and the National Institutes of Health (among others) was published in the New England Journal of Medicine on May 22, 2020.  Here is a quote from the article:

 

"Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection."

You might be interested to note that remdesivir was given to 538 patients (mean age 58.9 years) and a placebo was given to 521 patients.  Of the remdesivir patients, 334 recovered with a median time of recovery of 11 days and 32 patients died.  This compares to 273 recoveries for the placebo with  a median time of recovery of 15 days and 54 patients died.  Of the patients being treated with remdesivir, 36 had their treatment discontinued because of an adverse event or serious adverse effect (other than death) and 13 had their treatment discontinued because they withdrew consent.  The key take-away from this test is that a course of remdesivir reduces the time of recovery from COVID-19 to 11 days from 15 days when the placebo is administered, a four day improvement.

 

Currently, remdesivir is authorized by the Food and Drug Administration for use in the United States under an Emergency Use Authorization (EUA) for patients with suspected or laboratory-confirmed cases of COVID-19, particularly in patients with severe cases with oxygen saturation levels less than or equal to 94 percent.  Here are the first three pages of the FDA Letter of Authorization for the EUA:

 

Now, let's look at the bottom line.  Gilead's CEO, Daniel O'Day posted an Open Letter on Gilead's website. as shown here:

 

 

Here is a key quote, keeping in mind that remdesivir was developed nearly a decade ago for a totally unrelated medical condition (i.e. it is being repurposed):

 

"We have decided to price remdesivir well below this value (the $12,000 savings that hospitals will realize by releasing patients up to 4 days early, thanks to remdesivir). To ensure broad and equitable access at a time of urgent global need, we have set a price for governments of developed countries of $390 per vial. Based on current treatment patterns, the vast majority of patients are expected to receive a 5-day treatment course using 6 vials of remdesivir, which equates to $2,340 per patient.

 

Part of the intent behind our decision was to remove the need for country by country negotiations on price. We discounted the price to a level that is affordable for developed countries with the lowest purchasing power. This price will be offered to all governments in developed countries around the world where remdesivir is approved or authorized for use. At the current price of $390 per vial, remdesivir is positioned to achieve the aim of providing immediate net savings for healthcare systems.

 

In the U.S., the same government price of $390 per vial will apply. Because of the way the U.S. system is set up and the discounts that government healthcare programs expect, the price for U.S. private insurance companies, will be $520 per vial. At the level we have priced remdesivir and with government programs in place, along with additional Gilead assistance as needed, we believe all patients will have access." (my bolds)

In case you are interested, here is Daniel O'Day explaining the company's pricing strategy, particularly its two-tier pricing strategy:

 

Let's close with this information from the 2020 edition of Gilead's Proxy Statement:

 

 

It certainly looks like none of Gilead's Named Executive Officers are going to have any problems paying for remdesivir should they require treatment.

 

Here is the conclusion about remdesivir from a May 22, 2020 paper entitled "The journey of Remdesivir: from Ebola to COIVD-19" by Joe Pardo et al which looked at the history of studying remdesivir as an antiviral drug:

 

"Infectious disease outbreaks have shaped the course of human history, and with every new outbreak come new challenges. Today, scientists and clinicians around the globe are fighting to halt the COVID-19 pandemic. A chief concern remains: there are no antiviral treatments proven to be effective in fully published, peer-reviewed, randomized placebo-controlled trials. Remdesivir has emerged as a promising candidate based on its in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. However, expectations should be tempered based on lessons from the past. Remdesivir has potent in vitro activity against Ebola virus, and was highly efficacious in an animal model of Ebola virus disease. Unfortunately, early hopes for a new paradigm in Ebola virus disease management were deflated with the completion of the first randomized trial. Remdesivir holds promise for COVID-19, but the first published randomized trial was underpowered and inconclusive. High-quality data are still lacking at this time. Thus, clinicians across the world now eagerly await complete results from additional randomized trials in COVID-19. Will remdesivir deliver?"

 

Yes indeed, we do know one thing.  Remdesivir will most certainly deliver one thing - profits for Gilead.

Addendum

Since I posted this, the United States Department of Health and Human Services has announced this:

Gilead will receive roughly $1.6 billion for its current and future supply of Remdesivir, between 90 percent and 100 percent of its production for the months of July, August and September 2020.  All this for a saving of 4 days of hospitalization per patient.  Oddly enough, an off-the-shelf generic drug, dexamethasone which is far less expensive has proven to reduce deaths by 35 percent in ventilated patients and by 20 percent in patients receiving oxygen only.  According to Drugs.com, injectable dexamethasone sells for as little as $41.15 for 24 one millilitre doses.

 

The Soleimani Assassination and Washington's Relationship with Tehran

Here is the latest news from Tehran according to the Tehran Times:

 

...from the Islamic Republic News Agency:

 

 

....from Iran Front Page News:

 

 

....and the Fars News Agency:

 

 

In case you have forgotten, the United States killed Iran's top general Qassem Soleimani with a drone struck in Iraq on January 3, 2020 (which seems to be a lifetime ago).

 

Here's what Brian Hook, United States Special Representative for Iran and Senior Advisor to the Secretary of State had to say in response:

 

"Our assessment is that Interpol does not intervene and issue Red Notices that are based on a political nature.  This is a political nature. This has nothing to do with national security, international peace or promoting stability ... It is a propaganda stunt that no-one takes seriously."

 

TO put Mr. Hook's comments into context, let's look at what he had to say about Iran in a recent virtual meeting with Jerry Seib on the Council on Foreign Relations website:

 

"So if you look at the Iranian economy writ large, exports are down. They are facing a massive economic contraction. That was even before COVID. Their access to foreign exchange reserves is minimal. Their government budget has big funding gaps that the regime has no idea how to fix. The IMF and the World Bank have both placed Iran’s economy as third worst in the world behind only Venezuela and Libya, which is not good company.

 

The Iranian regime relies on oil as its chief export to fund its malign behavior. And it’s really important I think on any strategy to counter Iran that you have to go after the oil. And for as long as we were in the Iran nuclear deal, we were not able to go after Iran’s oil exports. And in a very short period of time we have collapsed Iran’s oil sector. When we got out of the deal in May of 2018 Iran was exporting about two-point-five million barrels of oil a day. There was a Reuters story that had Iran’s export numbers for April at seventy thousand barrels a day.

 

This has been something that we promised to do. Secretary Pompeo in the speech that he gave after the president got out of the Iran deal, he gave the Iranian leaders a choice. He said: You can either come to the negotiating table or you can manage economic collapse. And so far, the supreme leader has made very bad decisions for his own people because he has been managing economic collapse now ever since. And so much of what we said we would do we have delivered on.

 

They have not come to the negotiating table yet, but that is something which the jury is still out on that. There is still plenty of time. What we have been able to do is to constrain Iran’s power projections by denying it massive amounts of revenue. And it’s really important for people to understand just how much Iran relies on its economy to fund its expansionist foreign policy, its sectarian warfare in the gray zone. Iran has conducted terrorist operations across five continents. They need money to do that. And this regime is facing an economic crisis that it has never before seen in its forty-one-year history."

 

It's nice to see that Washington, and in particular its Special Envoy to Iran, has such great pleasure in how they have managed to totally destroy Iran's economy and punish its people.  Nice job Mr. Hook.  You should be proud.

Hospital Profitability in America - An Unanticipated Consequence of the COVID-19 Pandemic

While those of us who live in advanced economies were told about the necessity of locking down during the COVID era to flatten the curve, thereby spreading out the disease and allowing the health care system to handle the massive influx of critically ill patients.  One might have thought that the influx of patients would lead to a financial windfall for the American hospital and for-profit health care system, however, a recent analysis by the American Hospital Association (AHA) would suggest otherwise.

 

AHA's analysis opens with this:

 

"America’s hospitals and health systems have stepped up in heroic and unprecedented ways to meet the challenges of COVID-19. As outbreaks have occurred across the country infecting more than 1 million people, hospitals have ramped up testing efforts and are treating hundreds of thousands of Americans in an effort to save lives and minimize the virus’ spread.1 This includes establishing testing tents, adding general and intensive care unit (ICU) bed capacity, and developing COVID-19 units to isolate and treat patients with the disease while safeguarding the health of other patients and hospital staff."

 

It goes on to note that the financial challenges faced by America's health care system have been historic thanks to the massive demand for medical equipment and supplies and disrupted supply chains which have led to increased treatment costs.  As well, frontline medical workers in heavily infected areas are being supported by their employers who have been providing them with child care, housing and transportation in some cases.

 

The AHA looked at the following;

 

1.) the impact of COVID-19 on hospital and health services costs.

 

2.) the effect of cancelled non-emergency services due to COVID-19 on hospital revenue.

 

3.) the impact of additional costs associated with purchasing and supplying personal protective equipment for hospital and health care staff.

 

4.) the cost of additional support being provided to health care workers.

 

Thanks to the cancellation of non-emergency services, and fewer visits to primary care and specialty care physicians, the number of inpatient and outpatient services has decreased by 13 percent from the previous year.  This has had a significant negative impact on hospital revenues. 

 

The AHA found the following:

 

1.) hospitals and health services have a net negative financial impact of $36.6 billion over the period from March to June 2020 including payments from COVID-19 patients.

 

2.) total revenue losses due to cancelled hospital services was $161.4 billion over the period from March to June 2020.

 

3.) additional costs associated with purchasing personal protective equipment totalled $2.4 billion over the period from March to June 2020.  This works out to roughly $600 million per month.

 

4.) cost of additional support to health care workers will total $2.2 billion over the period from March to June 2020.  This works out to roughly $550 million per month.

 

In addition, hospitals have experienced higher drug costs during the pandemic because of shortages related to broken pharmaceutical supply chains, higher wage and labor costs because of health care worker shortages and bonus pay schemes and additional costs for equipment like ventilators, ICU beds, COVID-19 testing tents among others.

Let's close with this information.  According to Becker's Hospital CFO Report, so far this year (between January 1, 2020 and June 22, 2020), 42 U.S. hospitals have closed or entered bankruptcy.  Here are some example of provider organizations which operate a combined 42 hospitals that have filed for bankruptcy or closed so far this year:

Our Lady of Bellefonte Hospital in Ashland, KY

Williamson Hospital in West Virginia

Decatur County General Hospital in Parsons, TN

Quorum Health in Brentwood, TN

UMPC Susquehanna Sunbury in Pennsylvania

Fairmont Regional Medical Center in West Virginia

Sumner Community Hospital in Welling, KS

Medical Center at Elizabeth Place in Dayton, OH

Mayo Clinic Health System in Springfield, MN

St. Vincent Medical Center in Los Angeles, CA

 

The American Hospital Association study concludes the following:

 

"Hospitals face catastrophic financial challenges in light of the COVID-19 pandemic. The AHA estimates a total four- month financial impact of $202.6 billion in losses for America’s hospitals and health systems, or an average of $50.7 billion per month."

Measuring COVID-19 Deaths Among the Elderly in the OECD

A new analysis by the Canadian Institute for Health Information looks at one key aspect of the COVID-19 pandemic that has received some coverage from the mainstream media; deaths among the world's most elderly and vulnerable population.  In the study, the authors examined statistics for 16 of the world's most advanced economies (i.e. the OECD nations), focussing on three key areas; cases and deaths, baseline health system characteristics and policy responses.  The authors note that there are some limitations to the study when it comes to international comparisons due to differences in COVID-19 testing regimes and reporting practices as well as how each nation defines long-term care (LTC).  Here are the key findings with statistics being current to May 25, 2020.

 

Let's open this posting with this table showing both the number of COVID-19 deaths per million population and the number of COVID-19-related deaths in long-term care per million population:

Here is a list of nations showing the number of COVID-19 cases and deaths among long-term care residents that occurred in each nation:

 

Australia - 67 cases, 28 deaths

 

Austria - 788 cases, 119 deaths

 

Belgium - 8,746 cases, 4,616 deaths 

 

Canada - 15,063 cases, 5,324 deaths

 

France - 73,435 cases,  13,539 deaths

 

Germany - 14, 128 cases, 2,835 deaths

 

Hungary - 172 cases, 33 deaths

 

Ireland - 5,698 cases, 897 deaths

 

Israel - 407 cases, 163 deaths

 

Italy - 30,012 cases, 10,629 deaths (data from 52 percent of LTC facilities in Italy)

 

Netherlands - 3,543 cases, 853 deaths

 

Norway - 163 cases, 136 deaths

 

Portugal - 658 cases, 327 deaths

 

Slovenia - 276 cases, 10 deaths

 

Spain - 29,516 cases, 17,730 deaths

 

United Kingdom - 191,138 cases, 10,102 deaths

 

United States - 150,000 cases, 30,000 deaths

 

 

Here is a list of nations with the percentage of COVID-19 deaths among long-term care residents as a percentage of all COVID 19 deaths for each nation:

 

Australia - 27.5 percent

 

Austria - 18.6 percent

 

Belgium - 49.6 percent 

 

Canada - 81.1 percent

 

France - 47.7 percent

 

Germany - 34.1 percent

 

Hungary - 6.6 percent

 

Ireland - 55.9 percent

 

Israel - 58.2 percent

 

Italy - 32.3 percent

 

Netherlands - 14.6 percent

 

Norway - 57.9 percent

 

OECD Average - 42 percent

 

Portugal - 24.65 percent

 

Slovenia - 9.4 percent

 

Spain - 66.1 percent

 

United Kingdom - 27.4 percent

 

United States - 31.0 percent

 

As you can see, Canada had, by a wide margin, the highest proportion of COVID-19 deaths occurring in long-term care.  This is significantly higher than its OECD peers which had an average of 42 percent of COVID-19 deaths occurring in long-term care residences.  In part, Canada's elevated level of deaths in its long-term care residences is due to the fact that Canada's LTC population tends to be older than other nations with 74 percent of residents being over the age of 80 years.

 

Let's look at two other interesting aspects of long-term care which partially explains why certain nations have such a high percentage of LTC deaths:

 

1.) Nursing aides, personal support workers per 100 LTC residents aged 65 and older and the type of funding in LTC:

 

Australia - 4.9 - private - user fees

 

Austria - N/A - public - insurance

 

Belgium - N/A - public - insurance

 

Canada - 2.3 - mixed public/private

 

France - N/A - private - user fees

 

Germany - 2.4 - public - insurance

 

Hungary - 0.2 - public - insurance

 

Ireland - 2.9 - mixed public/private

 

Israel - 9.7 - mixed public/private

 

Italy - N/A - mixed public/private

 

Netherlands - 5.6 - public - insurance

 

Norway - 8.6 - mixed public/private

 

Portugal - 0.5 - mixed public/private

 

Slovenia - 1.1 - public - insurance

 

Spain - N/A - mixed public/private

 

United Kingdom - 1.2 - private - user fees

 

United States - 4.0 - private - user fees

 

In general, nations with a higher number of nursing and support staff and centralized regulation and organization of long-term care had lower numbers of COVID-19 cases and related deaths.

 

Another aspect that influenced COVID-19 infection and COVID-19-associated death rates in long-term care facilities was the date on which there was enforced restriction of visitors to LTC:

 

Australia - March 18

 

Austria - March 5

 

Belgium - N/A 

 

Canada - March 17

 

France - March 11

 

Germany - April 2

 

Hungary - N/A

 

Ireland - March 27

 

Israel - March 10

 

Italy - N/A

 

Netherlands - March 19

 

Norway - N/A

 

Portugal - March 20

 

Slovenia - March 10

 

Spain - March 20

 

United Kingdom - N/A

 

United States - N/A

 

These statistics, particularly in the case of Canada, point to systemic problems of understaffing issues, particularly in the nation's private sector long-term care facilities.  Rather than focussing on the raw numbers of COVID-infections and deaths, it would appear that the world's media would be better serving the public need by pointing out the obvious flaws in the model of care that is provided to each nation's oldest citizens.

 

Mike Pompeo and the Death of the Two-State Solution

While the following question and answer session with U.S. Secretary of State Mike Pompeo on June 24, 2020 appears to greenlight Israel's unilateral annexation of at least part of the West Bank as quoted here:

 

"QUESTION: Hi. Israel may be annexing parts of the West Bank and Jordan Valley in a week, and Jordan has said annexation could kill its peace treaty with Israel. UAE’s Ambassador to the U.S. Otaiba said it would end any hopes of normalizing relations with the Gulf and Arab states. So my question is: How concerned are you about potential ramifications of annexation? And do you favor an incremental approach or an immediate annexation of 30 percent, as proposed in the White House peace plan? 

 

POMPEO:  Your first question was about Israel. We unveiled a Middle East peace vision some number of months ago now, and we’re continuing to work down that path. Decisions about Israeli and extending sovereignty in other places are decisions for the Israelis to make, and we are talking to all of the countries in the region about how it is we can manage this process for our end state objective. It’s, I think, the objective that the prime minister has certainly acknowledged he wants, right. He wants our Middle East peace vision to be successful. The Gulf states have all indicated that they are hopeful that we can put that in place. I regret only that the Palestinian Authority has refused to participate in that, right. They simply have rejected this out of hand. We simply asked that they come to the negotiating table based on what’s outlined in the Vision for Peace, and they have chosen not to. They have chosen to threaten, to bluster, to assert that they’re going to deny the ability to do security – that’s not good for the Palestinian people. It’s dangerous for the people that live in those places too.

 

What we’ve asked is for them to come together, for Israel and the Palestinian people to come to the table to negotiate a path forward and to find a resolution to this decades-long challenge. I remain hopeful that in the coming weeks we can begin to make real progress towards achieving that."

 

Thanks to the Washington Institute, we have maps showing several options for annexing the West Bank.  Let's look at two of them:

 

1.) Full annexation of all 130 settlements with 78 Palestinian communities (these enclaves would lie within the future Palestinian state but be under full Israeli control.  This would result in annexation of 29 percent of the total area of the current West Bank:

 

 

2.) All 52 Israeli bloc settlements within the barrier.  This would result in the annexation of 7 percent of the total area of the current West Bank:

 

 

While Mike Pompeo seems to be turning a blind eye towards Israel's annexation of the West Bank or any part thereof, there has been backlash from some key groups including a significant number of influential Jewish leaders:

 

1.) European Parliamentarians - 1080 European parliamentarians have signed a letter strongly opposing Israel's plan to unilaterally annex parts of the West Bank, warning that the move could be "fatal to the prospects of peace" as shown here:

 

 

2.) Israeli Policy Forum - Over 130 American Jewish leaders have sent the following to Israel's Alternate Prime Minister and Minister of Defense Benny Gantz and Israel's Minister of Foreign Affairs Gabi Ashkenazi :

 

 

3.) Commanders for Israel's Security - Israeli media outlet Haaretz featured a full-page advertisement by the Commanders for Israel's Security outlining their negative position on annexation.  In total, 200 Israeli generals and their equivalents signed this petition:

 

 

4.) Members of the United States Congress - 

 

 

In case you were curious, here is the text of House Resolution 326 which supports the two-state solution:

 

 

Israel's plan to annex any portion of the West Bank (beyond the territory already occupied by the significant number of Israeli settlements) would likely be seen as a move that will undermine the pillars of Washington's strategy in the region.  Given the West Bank's geographic proximity to Jordan, annexation could destabilize Jordan's America-friendly monarchy and it could impact Israel's growing relationship with Saudi Arabia, a nation that provides Israel with a territorial buffer from its archenemy, Iran.  Annexation may also prove to be very unpopular with everyday Israelis as shown in this article from Haaretz: