Hope and skepticism go hand-in-hand with vital measures in Covid-19 battle

gileadremdesivir-300x169Optimism and realism should not be oppositional characteristics when looking hard at the slowly evolving measures to deal with the Covid-19 pandemic.

Experts always have said many ways will be needed to battle the novel coronavirus and much attention has focused on a few: effective treatments, a vaccination, as well as testing, testing, testing.

There are reasons to be skeptical and hopeful about what is going on in each area:

The hunt for treatments

Public health officials have hailed the anti-viral drug remdesivir for offering modest hope in the effort to treat the coronavirus. In contrast to the unfounded hype, the guarded optimism about this anti-viral medication was accompanied by many caveats.

They said that the anti-viral — when compared against a placebo in a study in which participants and researchers also did not know who was getting the drug and who was not — shortened the time for ailing Covid-19 patients to recover. It did not appear to affect who survives the disease and who does not.

The announcement of these findings also drew fire because they were made so publicly and by the government and not the drug maker, and important data about the government-run clinical trial of remdesivir still has not been disclosed to the satisfaction of serious medical scientists.

And, even as American experts were talking up remdesivir, a study published in a British medical journal, based on a Chinese clinical trial that was halted due to a lack of participating patients, found no benefit to the drug when compared to a placebo.

Medical scientists have much to debate about what exactly was learned from clinical trials of remdesivir.

The practical concerns surrounding the drug are formidable, too, including whether Gilead, its maker, can supply it in quantity, who will get it, how will it be used (with best effect in early or late cases?), and how much it will cost. All these issues will be affected by the federal Food and Drug Administration decision to allow the emergency and temporary use of the drug in severe and diagnosed cases, as more testing on it goes on.

The company is saying the right things. But it has a history of dubious conduct. The firm has been embroiled in long-running disputes with patients over the costs and effectiveness of its drugs for HIV. Gilead was involved in a long controversy over the sky-high price of its Hepatitis C drugs, which cost tens of thousands of dollars per patient, reducing their viral loads so low they were effectively free of what had been a chronic, destructive disease. The company developed remdesivir as a potential therapy for the lethal, viral disease Ebola. It did so, advocates would later show, with almost $80 million in U.S. research aid and scientific support.

But early on in the coronavirus crisis, even as tens of thousands were infected and deaths had begun to mount, the company sought a special federal designation for remdesivir as an “orphan drug,” a medication for use only by a sliver of patients. Gilead asserted it needed the status to run tests on how the virus affected children. Critics, however, pointed out that the designation, if granted, would give the company giant intellectual property and liability protections, potentially guaranteeing it whopping profits. Gilead backed down.

As a potential Covid-19 therapy, remdesevir has its own challenges, too. It must be given intravenously, and it takes five to 10 treatments for optimal use, studies have found. It is not costly to make — and a coronavirus regimen might go for anywhere from $1-$29, experts have estimated. Gilead says it is ramping up production (see company photo above) and targeting to make enough of the drug for millions of people to be treated.

With the many questions buzzing around remdesivir, how it has been tested, and how it has attracted such attention, it may be worth looking back to the response to HIV-AIDS, in which Dr. Anthony Fauci, and the National Institutes of Health played big and crucial roles.

That viral crisis took a terrible toll on the nation, and from it, regulators and medical scientists learned excruciating lessons, notably fundamentals about viruses, how they work, and how to attack them and their harms. The AIDS epidemic officially began in 1981, and clinical trials of Retrovir, a key anti-viral drug also known as zidovudine or AZT, began in 1986. It won FDA approval in 1987, when its wider use showed benefits to patients. But its steep cost and dwindling effect over time, as well as harsh side effects, led many to ask why more treatment options were not available. Fauci stepped up in 1989 to speed testing of HIV-related drugs.

AZT stayed costly and difficult to get for a time afterward, further contributing to the rising numbers of HIV-AIDS deaths, so that, by 1992, HIV was the leading killer of men ages 25-44. It was not until 1996, with the pioneering work of Dr. David Ho, that researchers and clinicians developed a cocktail of three drugs that disrupted how HIV works that experts started to see the disease get controlled.

If remdesivir, indeed, points medical science on a productive path to squashing Covid-19, it will not be the only drug, as experts are diving in at a furious pace to study others. An intriguing line of research asks whether a roster of tens of thousands of existing drugs may be repurposed and be effective in surprising against the coronavirus.

In the meantime, some medications already are falling by the wayside, such as the arthritis drug sarilumab, marketed as Kevzara and made by Regeneron and Sanofi. Research shows it does not help patients who are hospitalized but not using ventilators, the New York Times reported. In some good news for the many who take prescription blood pressure medications, the many different kinds of these drugs don’t seem to play a role in making patients more susceptible to Covid-19 nor to affect the course of the infection, the newspaper also reported. For those with problem heartburn, a theory light on evidence has caused a run on Pepcid, an over-the-counter anti-acid remedy. And some studies question whether treating less serious cases of Covid-19, especially its dry cough, with certain over-the-counter remedies, may worsen the illness.

The quest for a vaccine

History shows that the development of vaccines to prevent diseases, especially viral sicknesses, can be fraught and slow. There is still no HIV vaccine. The mumps vaccine — considered the fastest ever approved — took four years to go from the collection of viral samples to the licensing of the inoculation in 1967. Researchers worked for a long time before a five-year span, which included killer outbreaks, accelerated the approval for an inoculation for the lethal, virus-caused, hemorrhagic fever known as Ebola.

Experts are staying optimistic that their work on a Covid-19 shot will be different. A nonprofit academic center devoted to vaccine research is a key reason why.

The Jenner Institute at Oxford has said that it will “schedule tests of their new coronavirus vaccine involving more than 6,000 people by the end of next month, hoping to show not only that it is safe, but also that it works,” the New York Times reported, adding this:

“[T]he Oxford scientists now say that with an emergency approval from regulators, the first few million doses of their vaccine could be available by September — at least several months ahead of any of the other announced efforts — if it proves to be effective.”

The newspaper said the institute had a jump on many others because of its earlier work, including long study of a possible inoculation against malaria:

“The institute’s effort against the coronavirus uses a technology that centers on altering the genetic code of a familiar virus. A classic vaccine uses a weakened version of a virus to trigger an immune response. But in the technology that the institute is using, a different virus is modified first to neutralize its effects and then to make it mimic the one scientists seek to stop — in this case, the virus that causes Covid-19. Injected into the body, the harmless impostor can induce the immune system to fight and kill the targeted virus, providing protection. Prof. Hill has worked with that technology for decades to try to tweak a respiratory virus found in chimpanzees in order to elicit a human immune response against malaria and other diseases. Over the last 20 years, the institute has conducted more than 70 clinical trials of potential vaccines against the parasite that causes malaria. None have yet yielded a successful inoculation. In 2014, however, a vaccine based on the chimp virus that Prof. Hill had tested was manufactured in a large enough scale to provide a million doses. That created a template for mass production of the coronavirus vaccine, should it prove effective.”

The Oxford experts have been more encouraged by recent U.S. testing of their vaccine in primates, a half dozen rhesus macaques that bear some of the closest biological characteristics of humans. The monkeys, after a single shot, have received heavy, multiple exposure to Covid-19 and have not become infected as would occur without the vaccine.

As the New York Times reported:

“A Chinese company, CanSino, has also started clinical trials in China using a technology similar to the Oxford institute’s, using a strain of the same respiratory virus that is found in humans, not chimps. But demonstrating the effectiveness of a vaccine in China may be difficult because Covid-19 infections there have plummeted.”

The newspaper reported on other efforts:

“Two American companies, Moderna and Inovio, have started small clinical trials with technologies involving modified or otherwise manipulated genetic material. They are seeking both to demonstrate their safety and to learn more about dosing and other variables. Neither technology has ever produced a licensed drug or been manufactured at scale.”

Fauci has announced that the U.S. government has launched “Operation Warp Speed,” an ambitious plan to develop and field a Covid-19 vaccine by January 2021, saying on the NBC Today Show:

“We want to go quickly, but we want to make sure it’s safe and it’s effective. I think that is doable if things fall in the right place.”

The newspaper also quoted Bloomberg news service reporting on the federal vaccine push, noting, “taxpayers rather than drug companies would shoulder the financial risk of failed vaccine candidates. Though costly, this could result in one being available months earlier than under the typical process. The potential January date would be on the early end of the 12- to 18-month timeline that Fauci has repeatedly given for a vaccine.”

The multistage process to test vaccines, including for their safety, has been neither fast nor easy, and it will be complicated as countries see their infections decline, reducing the possible clinical trial participants.

Even if medical scientists come up with a Covid-19 vaccine in record time, its effectiveness will not be clear for a while. The public, of course, has experience with a widespread and common inoculation for a virus — the seasonal flu. That shot seeks to protect patients against several strains of the illness, based on the best available research and disease forecasts.

But, even with long experience in their use, the shots vary greatly in how they protect individuals, notably because each of us, based on factors like our existing health, age, gender, and more, respond differently to immunizations. Studies by the federal Centers for Disease Control and Prevention show that flu shots have ranged in effectiveness in the last decade of between 19% and 60%. CDC studies show why, no matter the vaccine’s efficacy, it is important to get the shot and many others. The flu inoculation can ease and shorten the illness if people get the sickness, and larger numbers of vaccinated people increases the likelihood of “herd immunity.” That is the term for the protection that larger groups enjoy if more of their members have been vaccinated against an illness or have gotten it and recovered, with bodily resistance against it thereafter.

With a Covid-19 immunization, not only will questions need to be resolved about its effectiveness and capacities to scale a vaccine so it could be given to hundreds of millions around the globe, issues may arise as to which companies will work with what governments to undertake the formidable work of producing so many doses.

The British researchers, for example, talked with American drug makers. But — to their considerable credit — the institute has taken the position that their prospective Covid-19 vaccine should not be put out as a profit-gouging product. The Oxford folks ended up in a long-term deal with the European drug firm AstraZeneca, both agreeing to work on a “not-for-profit basis for the duration of the coronavirus pandemic … The institution and its spin-out company Vaccitech jointly have the rights to the technology used to develop the vaccine and they will receive no royalties from it while the COVID-19 pandemic persists,” U.S. News and World Report said. The Trump Administration has high expectations that an American, Western, or even South Korean or Japanese vaccine will be developed first and prove to be best. The United States, with the president’s xenophobic raging against Beijing, will be in a difficult place if the Chinese prevail.

The New York Times also reported that researchers may be aided on the vaccine front by not needing to develop a new inoculation but finding that “inherent immunity” may be helpful in allowing existing inoculations, like a shot for tuberculosis, to reduce Covid-19’s harms. It turns out that vaccines for one disease may kick up the body’s own defenses, producing important protections against other illnesses. This is not a substitute for a shot specific for the novel coronavirus. But the option may buy time until a Covid-19 vaccine can be developed, tested, and readied for mass use.

The turmoil over testing just won’t cease

How disconcerting is it that, months into the pandemic, persistent problems bedevil the crucial public health safeguard of Covid-19 testing?

Although state officials keep slogging to improve access to tests — including by skulking and working around federal officials to obtain them from overseas providers — the baleful lack of diagnostics for the novel coronavirus has gone beyond a national scandal, especially as state and local governments confront impossible choices about reopening and easing stern public health measures designed to deal with the pandemic. In a nation of more than 320 million, just over 6 million have been tested, meaning this country lags far behind President Trump’s false claim that America exceeds all other nations combined in testing. (Russia, Germany, Italy, Spain and United Arab Emirates have, in total, roughly quadrupled the U.S. totals).

There are, as the news site Vox has explained, two central types of testing — “genetic tests for Covid-19 (that look for active infections) and the serological antibody tests (that can identify past infections).”

Both types have accuracy issues, as Vox reported:

“Scientists at the Cleveland Clinic found that one popular rapid genetic test told users they didn’t have the virus when they actually did about 15% of the time. Meanwhile, researchers in California studied 14 antibody tests that were authorized by the Food and Drug Administration for emergency use and found that only three of them delivered consistent results. These findings add another layer of fog on top of an already murky situation.”

Members of Congress have expressed alarm that federal regulators — who have been assailed for their early bungling of Covid-19 tests — haven’t stepped up and tried to ensure the accuracy of blood antibody tests, especially as the number of providers for them has burgeoned and officials and individuals have expressed an urgent, greater need to rely on them. Sen. Chuck Schumer, the New York Democrat and Senate minority leader, has called on federal officials, too, to crack down on bogus and inaccurate home kits for Covid-19 testing.

The federal Food and Drug Administration — finally — has stepped in and gave test makers 10 days to submit data on the accuracy of their products or face steps to remove them from the market.

In the meantime, Los Angeles has become the first major city to announce that all its residents may be tested for Covid-19 infection, whether they display illness symptoms or not. Free exams will be conducted by appointment at drive-up sites across the sprawling city, the nation’s second largest.

To ease and speed up Covid-19 infection testing, some labs and governments have begun to use a different test developed by Rutgers researchers. It foregoes the use of long, uncomfortable swabs inserted deep in the nose in favor of saliva collection. This alternative requires fewer resources — not just the specialized swabs but also the personal protective equipment needed by trained health care workers to perform the nasal test. The saliva exam has equaled the accuracy of the nasal swab and it may detect infection earlier.

By the way for a deeper dig into the science of Covid-19 testing and the statistical and other gaps and challenges, this article may be worth a read, and this one, which explains a mathematical quandary rooted in Bayesian analysis.

In my practice, I see not only the harms patients suffer while seeking medical services but also the damages that can be inflicted on them by dangerous drugs, and the benefits they can enjoy by staying healthy and out of the U.S. health care system. The coronavirus threatens to swamp our health resources, which, in their better times, already had notable problems with infections acquired in hospitalsnursing homes, and other medical care giving facilities, as well as major challenges with medical error and misdiagnoses. That said, at this difficult moment, we need to support doctors, hospitals, and public health officials as they marshal science, evidence, and facts to battle the global menace of Covid-19.

We need, at the same time, to ensure that the race to find treatments and a vaccine for Covid-19 does not trample the rigorous science that safeguards patients from medical harms. We need to ensure the fair, appropriate access to coronavirus care, being darned sure that these stay affordable and that unacceptable price-gouging or unfair exploitation of government-funded research does not occur. We also need to stay optimistic and skeptical, keeping elected officials from espousing fantasy or falsehood and ensuring that long-promised basics in the battle against Covid-19 — like testing — is stalled no long. We have lots of work to do.

Patrick Malone & Associates, P.C. listed in Best Lawyers Rated by Super Lawyers Patrick A. Malone
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