Sarilumab, remdesivir, hydroxychlorquine, Regeneron, lopinavir/ritonavir, interleukin-6, Gilead. Say them as if your life depended on them.
As the COVID-19 death count mounts, tongue-twisting names of drugs, molecules, and drug companies have become the new lingua franca. Suddenly we’re all speaking pharma, even Donald Trump.
When the president touted hydroxychloroquine (HCQ), an anti-malarial drug, and remdesivir, an ebola drug, as potential COVID-19 cures during press conferences and on Twitter, international attention swung to highlight those unproven treatments. But they’re not the only drugs of interest in the desperate search for a cure. Amid some promising studies about various treatments, there are lots of contradictory claims, swashbuckling personalities, and big pharma players competing to be cast as heroes in this battle. The pharmaceutical trails that might lead to the other side of this nightmare are littered with demigods, dead ends, and media hype, but also some branches that are fertile and promising.
The likely reason you’ve heard more about hydroxychloroquine than any other treatment is the efforts of a pair of cryptocurrency bros who met on Twitter. Gregory Rigano, a 2011 honors graduate of Hofstra Law School, and James Todaro, a non-practicing ophthalmologist/bitcoin trader, had independently noticed reports from China and elsewhere that doctors were using the malaria drug on patients with COVID-19.
The pharmaceutical trails that might lead to the other side of this nightmare are littered with demigods, dead ends, and media hype, but also some branches that are fertile and promising.
Before the pandemic, Rigano had been touting a lower-cost, high-tech alternative to the traditional way pharmaceutical companies develop and patent drugs. In September 2019, he published a “white paper” using industry jargon to explain this initiative as “a marketplace for staking bio r&d digital assets in a censorship resistant p2p network where users have skin in the game. It is the first decentralized research organization DRO to accelerate bio-innovation via the monetization of information exchange, allowing anyone to create, license, and trade bio r&d digital assets.”
Translation: Rigano is proposing a way for those interested in curing a disease to come together without institutional barriers. A blockchain system would provide proof of each person, company, or institution’s contribution. This could entitle them to profit if research led to a patented cure.
Todaro, a graduate of Columbia medical school who did his ophthalmology residency in Michigan, had been offered a coveted spot in an established practice there upon his graduation, but he’d already started prospering by trading bitcoin. His medical school classes in epidemiology combined with his understanding that international events can have drastic consequences on the price of cryptocurrencies made him especially sensitive to early news of the novel coronavirus coming from China. This led to his March 10 tweet, “If you are an investor or trader in bitcoin and aren’t closely following the coronavirus pandemic, then you aren’t doing due diligence. Consequences could be poor health and a tough blow to your portfolio.”
If you are an investor or trader in bitcoin and aren't closely following the coronavirus pandemic, then you aren't doing due diligence. Consequences could be poor health and a tough blow to your portfolio. #Bitcoin #coronavirus
— James Todaro, MD (@JamesTodaroMD) March 10, 2020
Todaro noticed bits of news about chloroquine being used as a treatment. He knew about the drug because a side effect can be vision problems. “There was already a national shortage of chloroquine. This is what tipped me to its potential. The UK banned exports. China made some announcement that they were banning exports of ingredients for it.” Todaro told me in a phone interview. “And then I saw that no one in the U.S. and even Europe had come out with any sort of report that chloroquine was being used, or that there were studies it had been used against SARS virus. People were paying attention to remdisivir.”
When Todaro tweeted the next day about these signs that doctors outside the U.S. were recognizing the drug’s potential, Rigano tweet-replied with a video showing “s korea and china doctors are using chloroquine, very significant effect.”
Rigano and Todaro had been in communication previously about bitcoin, Todaro told me, without being specific. In closer contact now, Rigano told Todaro that he had been studying hydroxychloroquine for five years for another use, Todaro said, declining to specify for what. (I’ve been in brief contact with Rigano, but he has declined to answer specific questions.). With the rising pandemic, Rigano was now working on a paper compiling early research about using chloroquine to treat Covid-19 infection and asked Todaro to take a look. Having someone with an MD attached to the study could add legitimacy. “I was impressed by this summary of what I was seeing in different pieces around the internet,” Todaro said. “I added some medical knowledge to it.”
Within days, they published the co-authored study, and Elon Musk tweeted about it on March 16 with a link, “Maybe worth considering chloroquine for C19.”
Maybe worth considering chloroquine for C19 https://t.co/LEYob7Jofr
— Elon Musk (@elonmusk) March 16, 2020
That night, Rigano appeared on Laura Ingraham’s Fox News show, saying that French researcher Didier Raoult M.D./Ph.D was about to report that in a group of about 20 ailing COVID-19 patients put on a regimen of HCR and azithromycin, an antibiotic better know as Zithromax, all tested negative and were virologically cured within six days of treatment. Tucker Carlson had Rigano on a night later, and soon Trump was parroting the treatment optimistically in press conferences. “It may work, it may not work,” Trump said. “I feel good about it. That’s all it is. Just a feeling. You know, I’m a smart guy. I feel good about it.”
Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, who followed the president, dampened the gut-level enthusiasm, saying he would await proper scientific trials. Within days, news came of an Arizona couple who had self-medicated with a version of chloroquine used to clean fish tanks. Ill effects hit within minutes. The husband died of cardiac arrest and the woman was hospitalized in critical condition.
Doctors have been trying more measured versions of the treatment on the hospitalized—and on the rich and privileged. When David Bryan, 58, the keyboardist for Bon Jovi, came down with flu-like symptoms on March 15 after spending weeks in New York City working on previews of Diana, a musical he cowrote, he tried resting at home in New Jersey. By Wednesday he had shortness of breath and his wife insisted he see his doctor in Brick, New Jersey, Dr. Michael Rothberg. A positive COVID-19 virus test followed.
Dr. Rothberg had heard about the HCQ/Zithromax treatment and put Bryan on a five-day course, the musician told me in a phone call while still recovering at home. He knew about chloroquine before as a malaria preventative. “I’ve taken it,” he said. “I’ve been to 150 countries with my band.”
Is it the pills that made him feel better or just his own immune system? Impossible at this point to know. But Bryan went on a Fox Business show to discuss his progress, aiming to calm fears. His wife had also tested positive but only had two days of headaches, and did not take the prescription drugs. Acknowledging that there were people hospitalized and dying, Bryan said he nevertheless thought it useful to talk about the course of his illness and treatment in order to destigmatize COVID-19—just as the subject of his musical, Princess Diana, had done with AIDS. She is in a famous 1987 photo that showed one could safely touch skin with an AIDS sufferer without catching it.
“Princess Diana was one of the first to go to an AIDS ward and shake hands with an AIDS patient,” Bryan, co-writer of the hit Bon Jovi song “In These Arms,” said. “Knowledge overcomes fear. That inspired me do what I’m doing to put the knowledge out and calm the fear.”
Many news media reports have smartly highlighted the initial, flawed, results of the Raoult study, including a Los Angeles Times column and a New Yorker piece focused on the dangerous potential side effects of HCQ. A lot of reporters who, understandably, hate Trump and distrust everything he says, have clearly decided the HCQ stuff is dangerous bunk and moved on to other stories. But just because Trump likes it doesn’t make it all bad.
The French doctor has continued to update his results, and they are now based on a thousand patients. Other studies are also underway, and scientists including Fauci have cautioned that the Raoult study is not being done according to the most rigorous standards. But if you want hope along with your clickbait stories of people dying from fish tank cleaner, you could report it: as of Sunday March 29, the French study reported that of 1,003 patients treated with HCQ/AZ, only one had died.
HCQ is not the only promising treatment. Doctors from Mount Sinai in New York have begun siphoning blood from those who have recovered from COVID-19 in order to harvest their antibodies. These will be injected into hospitalized patients. Doctors should know by mid-April if it is helpful.
Meanwhile in a recent video address, Dr. Robert I. Grossman, the Dean and CEO New York University’s Langone Hospital system was bullish, but unspecific, about certain anti-viral drugs. “We continue to have signifiant numbers of Covid-19 admissions throughout our system. These patients vary in condition. I am happy to report that the vast majority of patients seem to be responding to treatments including our aggressive antiviral protocols. In fact a number of hospitalized patients have already been discharged. These are preliminary results but positive signs.”
Two decades ago, the New York Times made a famous miracle cure overreach with a 1998 front page article about angiostatin and endostatin, related drugs that were a potential cancer cure. This time around, the Times is being extra-super careful. “There is no antiviral drug proven to be effective against the virus,” Carl Zimmer reported circumspectly in a widely read New York Times story published March 18 and titled Hundreds of Scientists Scramble to Find a Coronavirus Treatment. The article focused on efforts at the University of California San Francisco to build a list of drugs that might have promise treating COVID-19, such as JQ1 a cancer drug that might shield human proteins the virus uses to reproduce.
Optimism about antivirals was further fueled by a New York Times piece comparing two young Chinese medical professionals who had become ill with COVID-19 and were admitted to a Chinese hospital the same week. One of the women lived and the other died. The nurse who survived the illness had received “a regimen of arbidol, an antiviral medicine used to treat the flu in Russia and China; Tamiflu, another flu medicine more popular internationally; and Kaletra [lopinavir/ritonavir cocktail], an HIV medicine thought to block the replication of the virus. [She] was taking at least 12 pills a day, as well as traditional Chinese medicine.”
The Zimmer piece devoted a few paragraphs to remdesivir, an antiviral agent developed by the Silicon Valley company Gilead Sciences that had been tried against Ebola, but was not effective for that disease and is not yet FDA approved. The Times linked to a paper showing that “remdesivir could eliminate the coronavirus from infected cells,” and noted that “five clinical trials have begun to see if the drug will be safe and effective against COVID-19 in people.” But until the results of the study are published we won’t really know.
As more patients arrive at hospitals, doctors continue to hope the list of proven useful treatments can quickly expand to include more than sedating people, intubating, and hooking them to whatever respirators are available.
UCLA started a remdesivir clinical trial in March. Dr. Otto Yang, an infectious disease specialist at UCLA, said he was not sure how much of a supply of remdesivir UCLA would receive for it nor how many patients can be treated.
“We don’t know,” Dr. Yang said. “We’ve been assured there’s a large supply for the study but we don’t know what that means.” He added that, “It may work. It may not. It does have some side effects.” Information had come out showing remdesivir could harm the kidneys in an animal study.
In mid-March, when UCLA had only a “handful” of COVID-19, patients, there was still another way to get remdesivir, through Gilead’s compassionate use program, which provided pills to critically ill patients on a case-by-case basis. But on March 23, Gilead announced it was overwhelmed with requests nationally and discontinuing the program to focus on clinical trials.
That same day, according to two spectacular articles in The Intercept about Gilead and remdesivir, the company was granted by the Food and Drug Administration “orphan” status for the drug, which would allow it to profit exclusively for seven years on remdesivir, potentially limiting supply and the development of lower-priced generics. The orphan drug law was designed to encourage research on drugs to treat obscure diseases, those that affect fewer than 200,000 people in the U.S. But a loophole applies if the designation is given before a disease reaches that threshold. As of March 31, there were more than 160,000 confirmed U.S. cases of COVID-19.
Joseph Grogan, appointed a member of the White House Coronavirus Task Force in January 2020, served as a lobbyist for Gilead from 2011 to 2017. Gilead has faced fire in the past for pricing. Its preventative HIV drug Truvada costs $6 to manufacture but treatment costs almost $2,000 a month in the U.S.
After a public outcry, on Wednesday, March 25, Gilead issued a statement announcing it had “submitted a request to the U.S. Food and Drug Administration to rescind the orphan drug designation it was granted for the investigational antiviral remdesivir for the treatment of COVID-19 and is waiving all benefits that accompany the designation. Gilead is confident that it can maintain an expedited timeline in seeking regulatory review of remdesivir, without the orphan drug designation.”
Gilead’s stock price, which had been rising, leveled off.
Evidence of how a big pharmaceutical company with a potentially winning drug against a pandemic disease can more clearly promise to act quickly is in a March 17 Barron’s article. Reporter Jack Hough spoke to Leonard Schleifer CEO of Regeneron. Their arthritis drug Kevzara was undergoing trials to treat lung inflammation associated with COVID-19. In China a drug in the same class, known as Actemra, had been used to treat 21 people, “and all of these people did very well. They all got out of the hospital,” Schleifer said.
“If [Kevzara] is shown to work in hospitalized patients, we have lots of the drug on hand and can make much more…. If we can enroll the study quickly over the next month, you should know within a few weeks of treating people how they’re doing.”
Schleifer’s company was also announcing its research had identified hundreds of virus-neutralizing antibodies that could potentially be used in a cocktail drug against COVID-19.
“We’re going to pick the best and manufacture a cocktail. We hope to get started testing patients in June and manufacturing at large scale by the end of the summer,” he said.
Dear reader. Don’t catch coronavirus until at least June! Ideally September.
Or at least mid-April. Unconfirmed reports began emerging that in addition to national shortages of chloroquine, there was a developing shortage of at least one brand of HCQ, called Plaquenil. Anecdotes proliferated across social media of dentists and anyone else with a prescription pad, writing prescriptions for HCQ and Zithromax to stockpile for their own friends and families. With fevers rising, the pharmaceutical company Mylan announced in a statement that it had restarted production of hydroxychloroquine tablets at its West Virginia manufacturing facility “to meet the potential for increased demand resulting from potential effectiveness of the product in treating COVID-19… The company is also taking steps to initiate production of this product outside the U.S. in the coming weeks….Mylan expects to be in a position to begin supplying product by mid-April, and with the active pharmaceutical ingredient that we currently have available, will be able to ramp up manufacturing to provide 50 million tablets to potentially treat a total of more than 1.5 million patients.”
Of course, even that would likely not be enough. They need more of that ingredient. How do they get it? Another question: Is that ingredient something that other countries have stopped supplying to the U.S., just as Britain has already banned chloroquine exports?
In any case, since the drug is an old one, it is unlikely to be a profit driver for Mylan, and pharmaceutical companies are well aware that this moment in history is an opportunity for them to confirm or dispel perceptions of them as heartless profit-mongers.
“There are some people who suggest we’re sitting around rubbing our hands together trying to figure out how to profit from the misfortune of this virus,” Schleifer said. “This couldn’t be further from the truth… People at BARDA [Biomedical Advanced Research and Development Authority] have realized that if they want to incentivize the industry to steer efforts toward these important diseases, and have shareholders take the risk, they have to have some marketplace. For a disease like Ebola, that might be a strategic stockpile, which we’ll compete for. Government purchases will be a way for companies to reasonably return something to their shareholders. We view that as important, but it’s not driving us. We want to do well by doing good.”
Who would dare suggest pharma profiteering? Journalists, flaws and all, have suddenly emerged as essential workers in a time of crisis. Our bullshit meters are nearly as prized right now as the home pulse oximeters that are now hot items on Amazon. This was made clear by the tragically infuriating news that a program started during the end of the George W. Bush administration to develop and stockpile a national emergency supply of low-cost respirators had been killed before any devices were delivered. The Costa Mesa company contracted to build them, Newport Medical, was taken over by a bigger medical device company, Covidien—yes Covidien—that was later swallowed in a $50 billion purchase by the device giant Medtronic.
“Government officials and executives at rival ventilator companies said they suspected that Covidien had acquired Newport to prevent it from building a cheaper product that would undermine Covidien’s profits from its existing ventilator business,” The New York Times reported.
Understandably, there is an anarchic, somewhat chaotic quality to the hunt for effective COVID-19 treatments and for news. After reading a fantastic phone interview a New York Post reporter had with a COVID-19 patient from his hospital bed in Ohio, I called the reporter, Rosemary Misdary. Her piece had delved deep into what the patient, Kevin Harris, had been through, and how close to death he’d been. But it was blurry if you were reading to discover exactly what doctors had given Harris to help his healing: “…a cocktail of vitamins—including lots of vitamin C—cough medicine, an experimental antiviral medication, a malaria vaccine and antibiotics. They told him they were trying to jumpstart his immune system. They also told him to pray.”
I called Misdary to ask if she’d gotten the name of the experimental drug. “I kept pushing him for what it was,” she said. “And he didn’t know, and the only people who did know were his doctors and I have’t been able to reach them.”
I texted the hospital spokesperson and tried reaching one of Harris’s doctors to get a specific name for the drug that had apparently helped the patient. No one has gotten back to me yet, and patient confidentiality rules mean they probably won’t.
An example of how we are each chaotically agglomerating information in this fog is the way I learned that “anosmia,” loss of one’s sense of smell, might be an early indicator of COVID-19. An old friend emailed that five of her six New York friends who are sick lost smell and taste before fever or sore throats arrived. I logged this as an interesting anecdote. Later that same day, I clicked on a tantalizing Twitter alert that studies were showing the virus was not mutating quickly, making it likely that an eventual vaccine would work permanently against it. The alert linked to a Washington Post article, which, in turn, had a link to “Losing sense of smell may be a hidden symptom, doctors warn,” where it was reported that “a team of British ear, nose and throat doctors … warned that adults experiencing recent anosmia could be unknown carriers of COVID-19.” The British Rhinological Society, had been trying to raise worldwide awareness for days, “but it hasn’t been picked up,” one doctor said.
The fight against the virus is a World War, and the fog of war is real, a miasma of information real, tentative, and false, complicated by emotion and the fatigue of the observer.
The symptom was confirmed back on Twitter by Rudy Gobert, the Utah Jazz center whose positive coronavirus test had prompted professional basketball to shut down: “haven’t been able to smell anything for the last 4 days. Anyone experiencing the same thing?” But then other doctors, from the World Health Organization, were wary of triggering an international loss-of-smell panic and cautioned that more study was needed.
The fight against the virus is a World War, and the fog of war is real, a miasma of information real, tentative, and false, complicated by emotion and the fatigue of the observer. In trying to report clearly through it, I received inaccurate news tips by text from friends. A British TV producer told me Prince Phillip had died. The wife of a hedge fund titan alerted me that Trump had fired Fauci. Neither tip was true. Meanwhile Floyd Cardoz, a world-class chef I knew personally, died of COVID-19; a close friend, Brooklyn reporter Gersh Kuntzman, who had just been at a press conference with New York Mayor Bill de Blasio, called me coughing profoundly with a fever; and another friend who’d fled to her family’s country house with her husband and children messaged a group text of old friends that “I have it.”
There is a way to stop relying completely on the mediators. If you want to really go deep into this, head to a website, medRxiv.org, that publishes medical studies, usually before they are peer-reviewed and certified. It is in overdrive right now with preliminary work on COVID-19 (AKA SARS-CoV-2). Reporters rely on it, but they do not catch everything.
For instance, the South China Morning Post, reported on a particularly interesting study in China a day after it appeared on the medRxiv site. The study concluded that “People with blood group A have a significantly higher risk for acquiring COVID-19 compared with non-A blood groups, whereas blood group O has a significantly lower risk for the infection compared with non-O blood groups.” Other outlets picked up the report the next day. But there’s news amidst the studies posted on medRxiv that no one appears to be picking up. Here’s a study posted the following day, March 17, by a different set of Chinese doctors that I came across that adds heft to the other one about blood types and also shows that certain promising antiviral drugs won’t work to save everyone. I haven’t seen it reported on elsewhere. “Retrospective Analysis of Clinical Features in 101 Death Cases with COVID-19″ concludes that among 101 deaths at Wuhan Jinyintan Hospital, “males dominated… Importantly, we found that the blood group distribution of the deaths [is] (A-42.57%, B-30.69%, O-17.82%, AB-8.91%).”
So not only are certain blood types more prone to infection, they are also more prone to death.
Of those who died, “60.40% received antiviral drugs, including oseltamivir, ribavirin, lopinavir, ritonavir, ganciclovir, or interferon, etc.”
That some of the patients who were given the lopinavir/ritonavir cocktail died does not necessarily mean the drugs won’t work against COVID-19. It could suggest that at whatever dosage it was given in these cases, it won’t always work.
Samples of some of the other 600-plus medRxiv articles include one from March 28 to give pause to anti-vaxxers, a study showing that countries with a long history of administering the anti-tuberculosis vaccine Bacillus Calmette-Guerin (BCG) to children are showing less COVID-19 impacts across all ages in early data.
“National differences in COVID-19 impact could be partially explained by the different national policies in respect to childhood vaccination,” the study found. It is possible that countries like the United States and Italy that do not have universal BCG vaccinations were being hit particularly hard.
It concluded that “the combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19.”
From the medical fight to the political one, there’s a lot here, including “Estimating unobserved SARS-CoV-2 infections in the United States.” Posted March 18 by American academics, it concludes that unobserved SARS-CoV-2 infections in the U.S. by March 12 (the day before the U.S. Government declared a national emergency) likely numbered in the tens of thousands, and quite possibly in excess of 100,000.
In other words, as the President was downplaying the risk of COVID-19 here, it’s possible the disease had already infected 100,000 Americans. This “suggests that the U.S. was well past the possibility of containment by March 12.” The authors continue that if social isolation and other “efforts begin to reverse increases in SARS-CoV-2 transmission in the U.S.,…a downturn in COVID-19 deaths may not appear until several weeks later.” But it can happen, since China’s efforts to isolate mass populations “provide reason for optimism that they can be effective.”
You’ll have to wade through a lot of dense material to find these nuggets, but this may be the only way for the deeply curious to get their coronavirus news fixes such as: “Effects of temperature variation and humidity on the mortality of COVID-19 in Wuhan,” published March 18 by Chinese scientists. The details are complicated but in sum, the study suggests temperature variation and humidity may be important factors in determining how deadly COVID-19 is.
An Australian study from late February studied a patient with a “mild to moderate” version of the disease. It concluded that once the patient recovered, they had “substantial anti-viral immunity,” meaning they appeared to have emerged with resistance to the disease.
This has been a very hard story to finish, possibly because I am a mild hypochondriac who does suffer from asthma, one of the underlying conditions known to make people at any age more susceptible to a bad outcome from COVID-19 infection. Procrastination is easier than doing as maybe you are too, feeling anxious every time I read another article about the death count and clear my throat—why did I do that? Is it starting?
When my doctor prescribed a new inhaler, it was delayed, and when I phoned my insurer’s pharmacy to find out why, the computer-generated voice that tells you wait times are “between seven hours and 23 minutes and 11 hours and 17 minutes.” I hung up and googled albuterol inhalers and COVID-19 and found out that the “rescue inhalers” many asthmatics carry around are being used in emergency rooms now to reduce lung inflammation from the virus. The normal method hospitals had been using for asthma attacks, a nebulizer of albuterol, creates an aerosol that, a theory goes, could spread the disease in a hospital, so the smaller inhalers are now being ordered by hospitals in bulk.
Mine did come by mail to my home, along with a longer-acting steroid inhaler and a bottle of eight alprazolam pills (generic Xanax) to be used in case of severe anxiety. Might the steroid make me more prone to infections? Could be. But the doctor said it would be best to get my lungs nice and quiet just now. I’m puffing twice a day and being religious about a daily Allegra and snorts of Flonase against seasonal allergies. Keep the pipes clear.
Like you I want good news. I want to believe that as with AIDS, all of this study will lead to the development of useful treatments for a range of diseases. Maybe somehow all this will help with cancer, with global warming, with spreading the supportive virtual communities we’ve seen spring up this past month thanks to broadband internet by bringing this modern wonder to those who want it at a fair price wherever they live. I want to keep breathing.
I don’t have a pithy conclusion here. Best I can do is circle back to David Bryan, who has performed “Livin’ on a Prayer” countless times, and hope that somehow, someway we are halfway there.
He said, “It’s a nasty virus.”