What Lies Beyond Hydroxychloroquine…?

How do you figure out what medications might be most effective in fighting COVID-19? And fast!

We all know by now the President says he’s trying out hydroxychloroquine, because he feels the malaria drug might be good for protection against COVID-19. And while the President is rightly criticized for continuing to flog it as a “magic bullet”, based on his gut, that doesn’t mean looking into whether it might be effective wasn’t worth a shot. As long as it’s not to the detriment of the development of other treatments out there which might be more effective.

Because most likely, any near-term chance of a treatment, prophylactic or remedy will come from an unintended use of an already existing drug. No doubt, it’s much easier to make, distribute and prescribe a drug that already exists for something else, than to develop a new one, which would require several levels and probably years (usually more than 10 years) of development and testing to make sure that both:

  1. It works.
  2. It’s safe for humans to take.

According to the FDA, there are right now in the U.S.:

“Over 20,000 prescription drug products approved for marketing”.

Which quickly becomes millions when they’re prescribed in combination by doctors as “cocktails”, because they’re known to work better together for certain diseases or conditions. In fact, a quarter of all Americans take 3 or more prescriptions drugs. Half take at least one. And that number goes up with age, with nearly three-quarters of Americans between the ages of 40-79 taking at least one prescription drug, all according to the CDC.

And that’s good news in a way, as it relates to Coronavirus, because the fact that so many people are taking so many medications has historically given physicians and researchers a lot to work with in terms of turning anecdotal side benefits into medical breakthroughs. For instance, one tuberculosis vaccine that we’ve written about before because it’s being looked at as potentially beneficial against Coronavirus, has been successfully used for years to treat bladder cancer. But no one knows why it works for that. More famously, the hair growth drug Rogaine was originally developed (and didn’t work) to treat ulcers. And Viagra was supposed to be for heart related chest pain. Their eventual uses were just serendipitous side effects.

So how do you sift through every individual drug, and all these cocktails without it being completely random and hit-or-miss? How do you know which to prioritize? How can you figure out early which might be worth looking at further?

If we had to guess, we’d say the first place you’d look is at drugs that have been used to treat (or tried to treat) viruses before, especially similar viruses. HIV drugs, influenza drugs, hepatitis drugs, drugs that were used to treat SARS and MERS: virtually any anti-viral drugs out there. That’s just common sense. The best example of that so far is Remdesivir, which is a drug that was originally developed to treat hepatitis C, and was tested for use in fighting Ebola. And recently, there’s been some evidence (based on a study) that it helps shorten the recovery time of hospitalized patients with COVID-19.

But what about the idea of just going around and starting to test everything? Wouldn’t that be a waste of time, and counterintuitive? Turns out maybe not. A broad-brush approach is kind of breathtaking both in terms of the scale required, and also the fact that it can be done in a systematic way at all. But it can.

Because guess what? There’s a “library” affiliated with Scripps Research in California, that contains tens of thousands of tested compounds that have either been approved by the FDA or determined to be safe for humans (meaning they were safe to use, but just didn’t work out as drugs to treat what they were intended to treat).

And leveraging that may be starting to yield results or at least point to some promising paths in some very unusual places.

One of the most fascinating things we’ve come across recently, is a pre-print by a large group of scientists who took “12,000 clinical-stage or FDA-approved small molecules“–that is, existing treatments for all kinds of stuff–and started testing them one-by-one to see if any happen to protect cells against COVID-19. And they came up with 30 promising candidates.

This is a little figure they provided, showing what they did:

So basically, they’re infecting cells with Coronavirus, and seeing what happens if they’ve been treated with various drugs that are already around.

Say the study’s authors:

There is an urgent and critical need to identify novel medical countermeasures both for prophylactic and treatment use. Since the production of a vaccine could take 12-18 months13, and de novo development of therapies usually requires 10-17 years14, repositioning clinically evaluated drugs represents one of the most practicable strategies for the rapid identification and deployment of treatments for emerging infectious diseases such as COVID-19.”

Among the drugs they’ve found that made the first cut:

  • One intended for leprosy (but has also shown promise in treating gastrointestinal parasites),
  • Another for psoriasis (but didn’t work that well for that),
  • One for treatment of herpes,
  • Another for arthritis and multiple sclerosis,
  • One for Crohn’s disease,
  • An antihistamine,
  • A not-terribly-successful sleep drug,
  • As well as a couple of additional anti-malaria drugs.

Although the study’s authors note anti-malaria drugs are typically better at treating malaria (which is a parasite) in humans than viral infections, because:

The concentration required for their antiviral activity could…likely be difficult to reach in humans, without causing adverse effects.”

As we mentioned before, some of these drugs are already FDA approved for their original purposes. Others were in Phase I or II clinical trials, but then abandoned, because they didn’t prove effective in treating the diseases for which they were originally intended. But they were at least far enough along to determine if they’re safe. And at least one has been withdrawn from use in many places because it’s known to have serious side effects, including “fatal arrhythmias” and dangerous interactions with other drugs.

So which of all these might work best? Nobody knows yet. The authors of the study suggest it might very well be a “cocktail” of more than one. But at least it points forcefully to a direction for clinical trials, which are proceeding in earnest all over the place.