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FDA Insight: Episode 4 – Transcript

>> Anand Shah: Okay. Welcome back to another episode of FDA Insight. I'm Dr. Anand Shah, the deputy commissioner for Medical and Scientific Affairs here at the FDA. Thank you so much for joining us for our fourth episode. This week, we'll be discussing COVID-19 therapeutics and clinical trials. My guest today is Dr. Patrizia Cavazzoni, the acting director of the Center for Drug Evaluation and Research here at FDA. Dr. Cavazzoni, welcome to FDA Insight. Hope you're doing well and staying safe.

>> Patrizia Cavazzoni: Thank you for having me.

>> Anand Shah: Well, Dr. Cavazzoni, let's jump right in. What treatments are available for COVID-19?

>> Patrizia Cavazzoni: Well right now, there are no treatments that have been approved for COVID-19, but we have lots and lots of clinical trials and studies underway. What we have seen so far is many researchers and really wanting to test existing therapies for other conditions, other than COVID, that might be promising for the treatment for COVID, so we have looked at over hundreds of these types of potential therapeutics. What we're also seeing more recently after the wave of interest to look at existing drugs that might be repurposed for COVID, is now a really big push to study treatments that have been developed in a fit for purpose way for COVID. And an example of this is a class of very promising therapies that we hope will make a difference, which consists of antibodies that are developed in a manufacturing facility rather than in the human body, that if they work, will have the ability to neutralize the virus and prevent it from sort of attacking the host. So that's an example of some of these promising therapies that do not represent previously used drugs that might be repurposed for COVID if it turns out that they work in clinical trials that are really developed specifically for COVID.

>> Anand Shah: So how can folks get access to these investigational treatments?

>> Anand Shah: So we have a well-established expanded access, also referred to often as a compassionate use program, whereby physicians and treating physicians can apply on behalf of their patients, their individual patients, or we have also a program that allows a physician or a hospital to establish a program of expanded access that includes multiple patients. These applications, or these requests, have to really require the collaboration of the manufacturers of the drug, so the manufacturer of the drug who are studying the potential therapeutic, need to have this program in place, and then approve the utilization of the drug. So it takes really a triad of the treating physician, who makes a request on behalf of the patient, the manufacturer, very often this is a pharmaceutical industry, and FDA. And these requests are reviewed and approved. We understand the very often, or the overwhelming majority of these requests, particularly for COVID, entail very, very urgent situations where the patient may need a therapeutic very quickly. So we review these requests very, very quickly so that we can offer some options while we continue to work very hard to develop and review therapeutics.

>> Anand Shah: So, the FDA's been very busy over the past six months. Can you give us a window into what the FDA has done to support the development of new therapies for COVID 19?

>> Patrizia Cavazzoni: Well certainly this has been an unprecedented level of activity for FDA and particularly for CDER but also for other areas of FDA, of course. And very quickly we realized that we were dealing with an unprecedented circumstances, and we needed to adapt very quickly to this new reality. And so we created very quickly a program that allows researchers and commercial pharmaceutical companies who are developing a COVID therapeutics, to access us very quickly. We created a website that would allow researchers to submit ideas or proposals very quickly to get our input very early on so that we -- to get our advice and our technical input and they don't have to sort of guess what might be required to continue to study the drugs. We provide that early advice and then after that the researchers are able to incorporate that advice into their request to us to be able to start a program moving from the test tube into real, live patients. And we have a number of teams behind this program that are looking at the requests when they come in, and make sure that they get to the right place within our organizations, and then channel these requests to the appropriate areas within our centers, so that they can be reviewed by experts who are really very knowledgeable about that specific area or that specific type of therapeutic.

>> Anand Shah: So many of the drugs being tested against COVID-19 have already been approved by the FDA. Does that mean that they're safe to take?

>> Patrizia Cavazzoni: No, it doesn't. So as I mentioned earlier, there has been a really big momentum to look at the drugs that are approved for other conditions to see how they work and to see whether the mechanism by which they work could actually make them useful for COVID. However, in order to determine whether that initial idea that the drug might work results in proving that the drug is safe and effective for COVID, we need clinical trials. And so we need to determine whether the drug actually works against the virus. And so we cannot make the assumption that even if there is a hypothetically a way, a mechanism, for the drug to work against COVID, that it will actually work. And that's why we need well-defined and appropriately-sized clinical trials, so that we can make that determination.

>> Anand Shah: So social media's a huge part of how the public gets their information. Is that the right place for people to get information? Are there more reliable sources? I'm, of course, making an exception for our podcast series today.

>> Patrizia Cavazzoni: Well, the series is actually a really good example of providing a source of information that is reliable. We also have a lot of information on our FDA website, and I would really encourage the listeners to mine our website because we have a entire page around this program that I'm talking about, it's called the CTAP program of the COVID therapeutics acceleration program. A lot of information there. Certainly, I know that lots of listeners will rely on social media. At the same time, obviously, the information on social media does not go through the level of verification that we apply when we provide information to the public on our websites. So I would really encourage looking at the FDA website because there's so much information there.

>> Anand Shah: And I agree, Dr. Cavazzoni. I mean, we continue to update the FDA website, you know, daily. Oftentimes, multiple times a day. Just to pivot here, what are some of the dangers of off-label use of drugs? You and I are both physicians. We've both had busy clinical practices. And oftentimes, you know, there's a discussion of off-label prescribing. Can you talk to us a little bit about that?

>> Patrizia Cavazzoni: Well, some of the dangers, and I would say the biggest danger, is that in many instances when a drug is used off-label, there isn't sufficient information to indicate whether the drug is safe or effective for that off-label use. And then by definition, FDA has not determined that that drug is safe and effective. And why has that determination not taken place? Is because the right kind of studies, meaning the types of controls, reliable studies that I was referring to earlier, have not been conducted for that off-label indication. And so what happens is that physicians have left with having to make a determination based on what they know, maybe through their continuing medical education, or what — the literature that might be out there, which may or may not represent the type of studies that we would trust. Or their individual clinical experience to make these decisions without really having had a — having the sort of the type of information that a drug that's been approved by FDA would require starting with, again, the clinical trials, and then the reflection of that information in the label for an approved condition. And obviously the label is extremely important for clinicians because it provides information — all of the information that we know about the drug from the tests in the test tubes to clinical trials, and so on. And if the drug is not approved for a condition, the information is, you know, cannot be reflected in the label, for the most part.

>> Anand Shah: And Dr. Cavazzoni, what's the difference between a drug that receives an emergency use authorization, or EUA, versus a drug that is FDA approved? The public and the media frequently conflate these two concepts.

>> Patrizia Cavazzoni: The EUA is a mechanism that has been — really been created for a situation such as the one that we're in now with COVID. And it really tries to address a situation where there are no adequate, approved, and available alternative treatments for a condition, as we currently have with COVID. And so when it comes to an EUA, in order to decide whether to grant it or not, we have to satisfy ourselves that the known and potential benefits of this proposed treatment outweigh the known and potential risks.

>> Anand Shah: Dr. Cavazzoni, we talk about benefits and risks and oftentimes we accrue that data and that knowledge through clinical trials. Can you tell us a little bit about the purpose of clinical trials, specifically how does that information factor into the FDA's approval process? And if patients are interested, how can they go about enrolling in a clinical trial for COVID-19 therapeutics?

>> Patrizia Cavazzoni: Clinical trials are really the foundation of FDA's ability to determine whether a drug is safe and effective for treatment of a given condition. And so they are essential and they need to be the type of clinical trials that are able to give us data that we can interpret. And overwhelmingly, the types of clinical trials that I am referring to are what we call controlled, randomized clinical trials where the treatment is assigned randomly and where there is a control group, either a sugar pill or the usual type of clinical care that serves as a comparator to the group that receives the drug that is being investigated. And those are really the gold standard for us to be able to determine whether the drug works, is it effective for the proposed condition, and is safe. When it comes to enrollment in clinical trials, there is a great resource for patients under clinicaltrials.gov. There is a requirement for researchers to post the clinical trials that they are conducting on clinicaltrials.gov. The database is easily searchable by condition so patients and members of the public out there who are interested in participating in a clinical trial can do a search for COVID and coronavirus. And then visualize all of the trials that are ongoing with contact information.

>> Anand Shah: That's really helpful information for patients. With that, let's wrap up this episode of FDA Insight. Dr. Cavazzoni, thank you for making the time to discuss this very important topic as we navigate the COVID-19 pandemic.

>> Patrizia Cavazzoni: I'm really happy to be there and thank you for the opportunity to share this important information with your listeners.

>> Anand Shah: In future episodes, we'll be discussing more topics, including COVID-19 vaccine development. As always, we'll be providing you insight, in plain language, to help you understand the products that we regulate, the issues that we face, and the processes that we follow. We hope you enjoyed this episode of FDA Insight. Please subscribe on your favorite podcast app of choice, such as Apple Podcasts, Google Play, and others. Thanks for listening.

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