Will There be a “Cure”? We Talk with the Former Commissioner of the FDA

In recent weeks, companies have begun to reveal initial findings on the development of drugs and vaccines to treat and prevent COVID-19. We speak with Dr. Robert Califf, former FDA commissioner and head of medical strategy and policy for Alphabet Inc. on the COVID-19 pandemic, current FDA regulations and the drug-approval process.

Hydroxychloroquine, Favilavir, Gimsilumab, Remdesivir—chances are you’ve read these names (even if you can’t pronounce them). These tongue-twisters are among hundreds of drugs and vaccines undergoing clinical trials to become the first FDA-approved treatment for COVID-19. 

Dr. Robert Califf, former commissioner of the Food and Drug Administration (FDA) and current head of medical strategy and policy with Alphabet, said that numerous clinical trials are ongoing, but that they need to be carefully planned out even amidst the urgency of COVID-19—a process that is arduous and often difficult to predict. 

“Since it’s a new disease with a new virus, no one knows what treatment will be effective. And so there are categories of potential treatments to think about,” he said. “There are direct antiviral drugs. There are antibodies that attack the virus. There are adjunctive treatments that could help out by helping the body’s defenses against the virus. And then there are things that I would call health services, like if you need to go on a ventilator—what’s the best way to provide the artificial respirations through the ventilator to a COVID patient?”

But for most treatments, the road from laboratory to market is a long one, with the first hurdles being time and money. 

The cost of funding a drug through these tests is steep, often requiring millions, if not billions, of dollars as well as several years of research. A Tufts University study found that the median cost of clinical trials alone could be upwards of $19 million, not accounting for earlier stages of drug discovery and preclinical testing. 

Even overcoming these first hurdles, however, prospects for drug approval are low.

“Over 90 percent of drugs that go into human clinical studies never make it to market either because they don’t work as you expected or they have a toxicity that you didn’t expect,” Califf said.

The FDA evaluates the safety and effectiveness of these drugs and approves their use for the market. Approval rates for new drugs have increased in recent years, but still rests at about 14%

But, of course, these timelines and numbers are under normal conditions, not necessarily those of a pandemic; the urgency of finding a life-saving drug and/or vaccine for COVID-19 is changing some of the ways that the FDA is operating. One of those ways is an Emergency Use Authorization (EUA), which allows for certain unapproved medical products to be available for use during public health emergencies. The FDA has granted EUAs during past public health emergencies involving Zika, Enterovirus and Ebola.

“[W]hen you’re in a crisis, there’s authority granted by Congress for the FDA to really speed things up and to take much more risk: weighing the potential risk benefit, but not requiring that all the evidence is already in place,” Califf said.

Both remdesivir and hydroxychloroquine were granted EUAs near the start of May for use in the treatment of COVID-19. Remdesivir is a drug that has previously been shown to have some effect on coronaviruses and has already shown some positive results from a phase III clinical trial, whereas hydroxychloroquine is an existing treatment for malaria and other diseases. Recent results, including a study by the New England Journal of Medicine, seem to suggest that hydroxychloroquine is not effective against COVID-19, although there are calls for a randomized controlled study to be performed.

Drug discovery and approval pathway. Image courtesy of ePharmacology

The speed at which both have been authorized for use has bypassed some important controls that would usually be in place. 

“At normal times, there’s a really good reason to have all those checks and hurdles to get over for the reason that I gave—most things don’t work,” he said. “And so if you didn’t have all those checks, you would end up with a whole bunch of treatments that were ineffective or dangerous on the market.”

Many of these controls check to ensure safe levels of toxicity, side-effects and overall effectiveness in treatment. Each stage filters out the number of drug candidates.  Pre-clinical tests use animal models to determine drug safety and effectiveness. In phase I clinical trials, researchers administer the drug to healthy individuals to determine drug safety and metabolism whereas in phase II and phase III trials, researchers evaluate the effectiveness of drug treatment and safety on a larger group of infected patients compared with existing medication or placebo.

Vaccines must also go through the FDA for approval of use. And while both vaccines and drugs are types of medical products, their functions and purposes differ. Drugs are needed to treat individual patients infected with a disease whereas vaccines are created with the view of being used to immunize healthy members in the community and prevent diseases. Drugs are useful for treatment of patients that have become sick due to the virus and are good while we wait for a vaccine, which would provide protection from catching the virus. 

That wait, however, looks to be long.

“The shortest I can imagine is a year from this summer. Some people are a bit more optimistic, some are a lot more pessimistic,” Califf said.

While the challenges are many to develop either drugs or a vaccine for COVID-19, Califf has been inspired by the speed and passion with which scientists, the government and corporations are working to find a life-saving cure.

“All these things are underway in record time. It’s a little bit chaotic because it’s a global pandemic and everybody wants to help and everybody’s volunteering,” he said. 

Amidst the chaos, Califf said, an important reassurance is the dedication of those making decisions, even if they are forced to make difficult ones.

“[T]hese decisions are made by full-time civil servants who have no financial interest in play and who really are vested with the public health as the primary mission,” he said.

While we are consulting experts in the field to get answers to important questions during this crisis, new information and studies come out almost every day and much remains unknown regarding COVID-19. Midstory encourages everyone to follow all public health and safety protocols and exercise extreme caution. You can find out more about Ohio’s ongoing coronavirus response at https://coronavirus.ohio.gov/

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