Waiting for the FDA

The WSJ reported yesterday that President Trump has “considered issuing an executive order greatly expanding the use of investigational drugs against the new coronavirus, but was met with objections from Food and Drug Administration scientists who warned it could pose unneeded risks to patients[.]” At the daily White House briefing President Trump strongly implied that help was on the way. The Journal report bears on our push to raise awareness of possible therapies and get some action on them. Our friend Brian Sullivan is the founder and chief executive officer of a sophisticated biomedical company. Over the past few days we have drawn on his review of the literature to put forward possible treatments of the Wuhan virus and his analysis of the data. Beginning with a response to a disparaging comment posted on Power Line, Brian updated us with these comments yesterday afternoon:

Why is the commenter so dismissive of “treatments that can keep the most severely affected alive long enough for their immune systems to catch up and kick out the intruding virus.” Isn’t that whole point of treating people – keeping them alive!

The articles you are posting are from front-line clinical researchers who are using insights about the virus’s replicative mechanism to find drugs capable of disrupting that mechanism. These researchers aren’t obstinate or ignorant; they are doing what we want our scientists to do – investigate. For instance, data from the chloroquine studies showed “certain curative effect” with “fairly good efficacy.” Patients treated with chloroquine demonstrated a better drop in fever, improvement of lung CT images, and required a shorter time to recover compared to control groups. Those results are worthy of follow-up. If these treatments are successful, and shown to be effective in reducing viral load in patients, in ameliorating their symptoms, and in increasing their likelihood of survival as a result, then that is a fantastic outcome.

Thank god the researchers in these other countries are pursuing these options. Perhaps these efforts will fall short. However, if some of these treatments prove to be effective, the potential reduction in fatalities in the SHORT-TERM could be very significant.

These researchers are working to solve the most immediate problem we face, which is the risk of death amongst those infected today. The world is concerned about this virus because of its high fatality rate in the elderly. The whole point of lockdowns is to reduce those fatalities by minimizing the vulnerable populations’ exposure to younger, asymptomatic infected individuals. We don’t need to shut our economy down every winter when the seasonal flu leads to 30,000 – 40,000 American deaths each year because the risk of fatality to each individual is low. Likewise, if these treatment reduce the virus’ lethality, particularly amongst the elderly, the entire risk profile of the disease shifts to a level that doesn’t require the extreme measures we are taking today.

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Private industry, health care institutions, and government each need to drive evaluation of potential treatments for Wuhan virus in a clinical trial setting. Depending on whether the drug is generic or on-patent, different funding and organizational approaches are required.

Generic drugs do not offer sufficient profit margin for the manufacturer to justify investment in clinical trials. For these generic drugs, public health authorities or healthcare institutions need to fund the clinical trials required to evaluate their effectiveness. Chloroquine phosphate, the anti-malarial drug, and lopinavir-ritonavir, the HIV drug combination, are examples of reasonably priced generic anti-viral agents that should be evaluated immediately in clinical trials. Trials of these drugs are underway in China and South Korea. An example of a US healthcare institution stepping up is the University of Minnesota. They are just now kicking off two clinical trials to study losartan, a generic high blood pressure drug, in Wuhan virus patients.

For drugs that are still on-patent, pharmaceutical companies have sufficient economic motivation to sponsor and fund the trials of their drugs. Gilead Sciences, the manufacturer of Remdesivir, already has at least two clinical trials underway to study Remdesivir’s effectiveness in patients with either moderate or severe disease. This is the drug US Patient 1 responded to so well.

Thankfully, private industry and institutions like the University of Minnesota can act on their own initiative to set up trials. There is still an important role for the federal government to support additional trials so that we have as many alternatives under study as soon as possible. The most important goal of the medical community today must be to quickly find the drugs that can effectively treat and reduce the risk of fatality in Wuhan virus patients. All hands on deck.

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In a French clinical trial with 24 Chinese virus patients, encouraging results were reported for two potential Chinese virus treatment regimens (see here).

After each day of treatment, patients were tested to determine whether they still had the virus. After six days of treatment:

• 90% of patients treated with hydroxychloroquine in combination with the antibiotic Azithromycin tested negative for the virus
• 60% of patients treated with the anti-viral hydroxychloroquine tested negative
• Only 10% of the patients who received no treatment tested negative

It is dangerous to infer too much from such a small data set. Nonetheless, these results show a large enough treatment effect that they are more likely than not to be non-random. As they say in the drug business, further investigation is warranted!

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Word is getting out:

See also Andrew Dunn, Business Insider, “A malaria pill from the 1940s has caught the eyes of doctors, analysts, and even Elon Musk as a potential coronavirus treatment.”

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