COVID-19 Update from IPD Analytics March 19th, 2020 Transcript
Veronica Fowler (00:19):
Welcome to IPD’s Drug and Clinical Review, the premier podcast for drug intelligence and pharmaceutical and therapeutic management strategy. I'm Veronica Fowler, your host, and I'm here today with Dr. Julee Oh, Dr. Leslie Fish, and Jeff Casberg, three of our Executive Clinical Pharmacy team here at IPD. Welcome to the show.
Leslie Fish (00:40):
Julee Oh (00:41):
Jeff Casberg (00:42):
Hi, Veronica. Happy to be here.
Veronica Fowler (00:43):
Today we’re covering the coronavirus, specifically potential therapies, what’s currently in clinical development, testing and where we stand with that, governmental initiatives, and impacts to the pharmaceutical industry, including impacts to payers, providers, and suppliers, as well as manufacturers.
Now, if you're new to us and this is the first time you're listening to the show, at IPD Analytics, we provide insight, transparency, and efficiency to stakeholders across the pharmaceutical industry by identifying, projecting, and quantifying the impact of brand, generic, and biosimilar launches in the marketplace. We offer various subscription-based products with data and analysis to subscribers in over 45 countries covering:
The drug life cycle, from clinical development to loss of exclusivity;
clinical formulary procurement and inventory control, insights for payers, providers, and suppliers;
brand and generic market impact forecasts;
and medical drug coding and reimbursement information.
We're headquartered in Aventura, Florida, and our team is composed of unique experts, many from the patent litigation field, many from the biosciences, and many who are clinical pharmacists, whom you'll actually be hearing from today.
Now, our show is normally syndicated exclusively to our subscribers, but since this epidemic is so rapidly changing and information dissemination is key, we decided that we would open up this episode to the public. For further updates from us, follow us on LinkedIn or check out our website at ipdanalytics.com.
And for press inquiries, contact email@example.com.
So, all of that being said, today will actually be our third installment of the COVID-19 update, and, of course, we're watching the numbers very closely. Understanding that they're changing rapidly, all of the facts and figures that we mention here today are relevant for the time of this recording, which is March 19, 2020.
That being said, Julee, can you start us off with an update on where we stand nationally as well as globally?
Julee Oh (3:02):
Sure, Veronica. Since we last spoke, the CDC website has updated the numbers in the U.S. that total cases now number 7,038 and total deaths number 97. And the WHO (World Health Organization) website keeps us updated on what's happening globally across the world. There've been total cases of 191,127 with deaths numbering 7,807.
Veronica Fowler (03:36):
So, yes, Julee, as you've said, since our last talk, those numbers have definitely grown dramatically. And, of course, the thought on everyone's mind is where are we on a vaccine for this. Leslie?
Leslie Fish (03:48):
Yes, so therapies for the coronavirus can be divided into prevention and treatment. Vaccines will be the most effective therapy for prevention. Please note, a vaccine for the coronavirus could take well over a year to come to market. However, on March 17, the National Institute of Health (or the NIH) announced that the first human vaccine trial for the COVID-19 was started. Even though as I just stated, a commercial coronavirus vaccine is likely more than a year away, the trial was started to assess the efficacy and the safety of the vaccine. The efficacy portion of the vaccine will be looking at whether the vaccine can stimulate the patient's immune system to make antibodies that can stop the virus from replicating and thereby preventing illness. This trial is very early. We call that a Phase 1 trial. ‘
The trial is going to enroll 45 healthy adults ages 18 to 55 years. Each will receive two shots 28 days apart. They're actually looking at three different doses (those are being tested). The vaccine itself was developed by the NIH and Moderna. Moderna is a biotechnology company. Interestingly, the first recipient of the NIH/Moderna vaccine told MSNBC that she signed up for the clinical trial because she was eager to help scientists with the response.
Veronica Fowler (05:18):
And so, Julee, we're hearing a lot of terms out there, including antivirals, antibodies, and anti-inflammatory agents. Can you just give us a rundown on what each of these are and how they work?
Julee Oh (05:32):
Sure, Veronica. Antivirals are drugs that actually kill or prevent replication of the virus, while antibodies are proteins that are made by a patient's immune system after an antigen enters the body. In this case, the antigen is the coronavirus. The antibody then destroys the antigen. Anti-inflammatory drugs do not necessarily impact the coronavirus itself, but impact the symptoms of the disease. One of the major complications of COVID-19 is acute respiratory distress syndrome (ARDS), where fluid leaks into the lungs making breathing difficult or impossible. Anti-inflammatories can help prevent the body's immune and inflammatory response, which occurs when the immune system overreacts and attacks healthy tissue and organs.
Veronica Fowler (06:27):
And I understand there are many of these therapies currently in clinical trials, can you take us through those?
Julee Oh (06:35):
Yes, Veronica. There are numerous drugs in clinical trials. Some of these drugs include antimalarials, such as hydroxychloroquine and chloroquine phosphate, those trials should begin fairly soon.
Other drugs include sildenafil citrate, a lipoic acid, Ebastine-Lopinavir-Interferon alpha combination or a combination of Danoprevir, Ritonavir, and Interferon, also mesenchymal STEM cells are being studied. A combination of Dipyridamole and remdesivir is being studied, and also remdesivir alone is being studied. We expect to know results by early April.
Washed microbiota transplantation is being studied. Even Avastin plus recombinant ACE2 is being studied. Bromhexine hydrochloride plus Arbidol umifenovir, favipiravir, and interferon a2b, a combination of those four products is being studied. Favipiravir alone is being studied. Methylprednisilone and thalidomide are also being studied. So there are a slew of different drugs with different mechanisms of action that are being studied right now.
Veronica Fowler (07:55):
Okay, and so since vaccines are still out about a year to a year and a half, I've read that antibody therapy maybe a quicker solve. Are those also being studied now?
Julee Oh (08:06):
That's correct, Veronica. Antibodies can actually be used as prophylaxis or prevention before exposure to the SARS-CoV-2 virus or as treatment for those already infected. And another term that we've been hearing is called hyperimmune globulins, and they're basically the same thing as antibody treatment. It's a plasma-derived therapy that has previously been shown to be effective in the treatment of severe acute respiratory viral infections, and now they may be an option for COVID-19. Hyperimmune globulins, as well as antibodies, work by concentrating the pathogen-specific antibodies from plasma collected from recovered patients or vaccinated donors in the future. Again, by transferring the antibodies to a new patient, it may help that person's immune system respond to the infection and increase their chance of recovery.
Some currently in development are Takeda's TAK-888. Emergent BioSolutions has initiated development of 2 hyperimmune polyclonal antibody products for the treatment and prevention of COVID-19. [Eli] Lilly and AbCellera Biologics are partnering to co-develop a therapy to treat and prevent the virus as well.
Veronica Fowler (09:10):
But since these antibody treatments will rely heavily on human donor blood, which we've seen in other therapies and isn't wholly uncommon, won't that pose potential issues with supply as we've seen with IVIG because of the reliance on voluntary donations? So I guess the real question is, do we have any other therapies that aren't dependent on these human blood donations?
Julee Oh (09:53):
Yes. In addition to using human plasma to obtain antibodies, recombinant technology is also on the horizon that avoids the need for human plasma. Monoclonal antibodies are proteins produced by the immune system that can neutralize pathogens. Antibodies are typically made in mice that have been genetically modified to have human-like immune systems, which means that when they're given to a patient, his or her immune system will not attack the antibody there. Vir Biotechnology and Biogen are partnering to develop and manufacture human monoclonal antibodies for COVID-19, as well as Regeneron, who's developing an investigational 2-antibody therapeutic, as well as a 3-antibody therapeutic, both of which have shown promise in treating other viral infections in the past.
In addition to that, Actemra and Kevzara, which are both IL-6 inhibitors are being studied. Normally the response helps fight infections, but if the immune system overreacts, it can attack healthy tissue and organs. In some COVID-19 patients, the immune response may be accelerating and damaging the lungs even after significantly diminishing the amount of virus in the body and blocking IL-6 may prevent the immune system to keep the body from attacking itself.
Veronica Fowler (11:12):
Well that sounds interesting, but have any of these drugs been proven yet?
Julee Oh (11:19):
And the answer is no. There is very little to no evidence, and we have not seen any results of the trials yet. We've seen numerous anecdotal reports, but note that case reports are not controlled clinical trials that can be validated. In fact, the World Health Organization said on March 18th that it would launch a multi-arm, multi-country clinical trial for potential coronavirus therapies in order to validate the current numerous small studies currently ongoing. And the study, which the World Health Organization hopes other countries will join, has been named the Solidarity Trial. Countries that have already signed on are Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain, Switzerland, and Thailand. The WHO also goes on to state that multiple small trials with different methodologies may not provide clear, strong evidence that we really need to save lives. The drugs to be tested are the antiviral drugs remdesivir, combination of the two HIV drugs, lopinavir and ritonavir, plus or minus interferon b and the anti-malarial drug, chloroquine.
Veronica Fowler (12:34):
But, we're seeing all of these news reports and things in the media saying that there are drugs out there that have shown clinical benefit. What can you say about that?
Leslie Fish (12:45):
So I can take this one, Julee. A recent news article stated that the HIV medications ritonavir and lopinavir showed a little benefit. The data from this was published in the new England journal of medicine on March 18th. The new England journal of medicine article stated that there was no benefit from these medications compared to standard of care. It is important to make sure that we are getting the information from a credible source, and just as importantly, what the data really shows.
Veronica Fowler (13:19):
And I think your point is such a good one – people should be reading the sources of this information rather than the stories referencing the information. The writers of these additional articles may be putting their own spin on it. That changes the meaning – little benefit versus no benefit.
Leslie Fish (13:36):
Yes. So let me discuss some of the information that has been in the news articles. There has been data regarding favipiravir shortening recovery time in patients with no symptoms or mild symptoms, data regarding favipiravir shortening, fever duration and more data regarding lung function, X-rays. Some issues with this data is that there was no definition of what a mild or regular case is. Definitions have to be made clear as far as the chest X-rays are concerned. It looks like in patients who received the medication, there was improvement in 91% of patients; in patients who did not get the medication, there was improvement in 62% of those patients. Again, we don't even know what improvement is defined as. Is it clinically significant? There are no published studies on this yet, just articles and reports. Could this particular medication be approved for mild or standard cases when first diagnosed? Maybe.
We also get news about remdesivir and it's very mixed. Some of the data looks like it could be moderately beneficial. However, there are concerns over increases in liver enzymes and other side effects. We don't have data on this either. What we also don't have data on is whether the virus itself can increase liver enzymes. Like the other medications, we need to see if this can be beneficial from mild or severe cases of the COVID-19 virus.
Veronica Fowler (15:16):
And so we've also been seeing in the news reports that there are medications that patients are currently on that are putting them at a higher or a greater risk. Is that true Leslie?
Leslie Fish (15:28):
Thank you for asking that Veronica. It’s an important question because there have been some circulated reports in a few different medications. So the first one I'm going to talk about are antihypertensives. They're known as ACE inhibitors or ARBs. So again, one of the circulating reports we saw that ACEs cause a greater risk for the coronavirus. To dispel these reports, the Heart Failure Society of America (AHFS), the American College of Cardiology (ACC), and the American Heart Association (AHA) published a statement that addressed these concerns.
The three organizations recommend continuation of the antihypertensive medications for those patients who are currently prescribed such agents for the indications for which they're known to be beneficial. These are heart failure, hypertension, and ischemic heart disease. The white paper also mentions that ARBs have been shown to reduce severe lung injury and certain viral pneumonias. Again, the recommendation is to continue the use of these important antihypertensive agents.
The second thing that I'd like to mention (in addition to the antihypertensive issues) is that there are also discrepancies as to if nonsteroidal anti-inflammatory drugs or insets are harmful in patients with the virus. French officials had suggested that the use of these agents should be avoided and that acetaminophen should be used in place. However, many physicians, both inside France and outside of France, countered that there is insufficient evidence to state this. Physicians can recommend treatment with acetaminophen. Instead, Dr. Gregory Poland, a Professor of Medicine and Infectious Disease and Director of the Vaccine Research Group at the Mayo Clinic in Rochester, Minnesota, said that without clarification of any new detailing effects, additional risks from nonsteroidal anti-inflammatories related to COVID-19 are questionable.
Veronica Fowler (17:33):
Well, now that we've covered therapies, let's turn now to testing. Leslie, where are we with that?
Leslie Fish (17:42):
So Veronica, we do have a lot going on as far as testing is concerned. On March 17, the FDA began allowing states to authorize laboratories to develop their own diagnostic tests for the COVID-19 virus without the government. The FDA Commissioner Steven Hahn said during a press conference that the State Department of Health can act as a surrogate for the FDA. In addition, labs will not have to pursue the emergency use authorization from the FDA, which is usually required. This will hopefully speed up the number of tests that are available.
Currently, the United States has capacity to run about 175,000 tests per week. Some other notes of interest: Roche announced it received emergency approval from the FDA for a new, much faster test. The tests can be run in high volumes on fully automated equipment; thus it could provide more results far faster than others. Roche says it can run 96 tests in about three hours for 24 hours, which means it can run up to 4,100 tests.
Other companies including Co-Diagnostics, Laboratory Corp of America, Quest Diagnostics, Denmark Diagnostics, and Becton Dickinson have either launched or are preparing to launch their tests. And finally, Opko Health’s BioReference Laboratories has partnered with the New York State Department of Health to provide further tests.
Veronica Fowler (19:16):
And Leslie, what can we say about the accuracy of these tests?
Leslie Fish (19:20):
So it is PCR testing, which is for viral load, which should mean that it should be accurate. What could impact test results are poor swabs or not enough viral presence.
Veronica Fowler (19:33):
And as far as the expense for all of this, I know the government has put together a coronavirus package to help financially. Jeff, can you touch on that?
Jeff Casberg (19:44):
Sure, Veronica. So as you stated, the U.S. government is implementing a comprehensive financial coronavirus stimulus package and most of the components are unrelated to the pharmaceutical industry, such as, you know, paid emergency leave, enhanced unemployment insurance, and food subsidies. But there are a couple specific items directly related to the pharmaceutical industry. First one is free COVID-19 testing for everybody who needs it, including the uninsured, so the payers will have to implement that. And, secondly, increased federal funds for Medicaid. These are the two items in this coronavirus stimulus package directly related to the pharmaceutical industry.
Veronica Fowler (20:27):
And, Leslie, I've heard that there have been many other actions taken on a state level. What do we know about that?
Leslie Fish (20:34):
Yeah, so first of all, the governors have been reducing the number of people gathering together. They do this by closing bars and restaurants and are only allowing for pickup at the restaurants. They're closing schools and they're really trying to reduce the amount of contact between people to slow or flatten the curve. Recently, Governor Andy Beshear from Kentucky expanded prescribing rights to pharmacists in light of the coronavirus. So, the law allows for Kentucky pharmacists to fill prescriptions for 30 days, including an emergency refill if they're not able to make contact with the patient's physician. In addition, if there is a need, pharmacists can operate temporarily in an area that is not designated by the pharmacy’s permit. And this actually means that they can assist with and set up mobile stations for the COVID-19 efforts. Finally, pharmacists can dispense needed medications to treat COVID-19 when they are FDA approved and indicated, as long as they followed the protocols by the CDC or the NIH or other public health officials.
Veronica Fowler (21:42):
Okay. So we've been talking a lot about potential therapies and government and state initiatives regarding the public. But, Jeff, what are the impacts that you're seeing to the pharma industry as a whole?
Jeff Casberg (21:55):
So within the pharmaceutical industry, I see three particular impacted areas. First impacted area would be to the payers or the health insurers. Next would be impacts to the pharmaceutical manufacturers themselves. And then lastly, I see impacts to the supply chain, people who produce and distribute the pharmaceuticals.
So, first let me start with impacts to the payers and the health insurers. A few moments back, we spoke about the requirements contained in the U.S. government stimulus package of COVID-19 testing coverage at no cost to members of health insurance companies and also at no cost to patients who don't have insurance at all, so that would be the first impact to the payers. Then there's likely to be increased physician office and hospitalization cost in 2020 and beyond for treatment of these patients that have COVID-19.
Telehealth. Telehealth is an area that is going to have needed increased coverage and access. Telehealth includes services such as tele-doctor visits, online monitoring of diabetes, and other conditions, so that's definitely an area of expanded coverage and growth in the health care industry.
Next would be prescription refill impacts to the payers. There's going to be increased requests for early refills or even expanding the window for refills to avoid patients going without their medications, especially for those patients who may be quarantined and cannot return to their homes. Most payers traditionally allow refills once about 60% to 75% of the days’ supply of a prescription that has passed. It's likely that may be relaxed during this period of COVID-19 crisis.
Also, off-label use. So off-label use is when prescriptions are approved by the FDA, they're approved for a specific indication. Off-label uses are when medications are used outside their FDA-approved indications, payers will likely see an increase requests for off-label use of medications. Especially for patients who have advanced disease and require, you know, high-cost medication for products like Actemra, Kevzara, interferon, and Avastin.
Julee also discussed investigational products. The payers will see increased use for coverage of investigational products and their associated medical service costs. And, lastly, out-of-network coverage. So when you have health insurance, many times you're required to stay in particular network of physicians or hospitals. During this time of COVID-19, there could be increased requests for out-of-network coverage due to, you know, lack of access for needed services in network or being stuck outside the network where your current insurance doesn't cover. So that covers the payer impacts.
Veronica Fowler (24:56):
And, Jeff, you also mentioned manufacturer impacts. Can you go through some of those?
Jeff Casberg (25:02):
Sure. There are going to be many impacts in the pharmaceutical manufacturers, but I'll just touch on a few of them. First would be especially to new drug approvals and new drug launches. So currently there are not as many, or very few at all, representatives out in the field visiting physicians, which is common practice in the industry. With this COVID-19, the representatives are staying out of the office, and this change can have a lasting impact on the pharmaceutical sales, moving representatives away from face-to-face promotion and a movement towards electronic pharmaceutical sales.
Another impact could be potential FDA approval delays. So, the FDA supplies manufacturers with anticipated approval dates; it's called PDUFA dates. The FDA has not announced that there will be delays, but there could be delays due to the FDA being shut down for periods of time.
And then, lastly, FDA advisory committee delays. The FDA also has these committees and they gather groups of experts from across the country to discuss the safety and efficacy of potential drugs for approval. These committee meetings usually occur a month or two in advance of the FDA's approval or denial decisions for approval of the drug. These committees could be delayed and cause delay in the future approval of those drugs. Currently, a couple important therapeutic areas, such as NASH and Alzheimer's, have scheduled FDA advisory committee meetings, and these meetings may be delayed.
Veronica Fowler (26:40):
Okay, and before we wrap up, Jeff, I know you mentioned also there may be some supply chain impacts. What are those?
Jeff Casberg (26:48):
No, you're correct. There could be significant impacts to the supply chain, which is the production and distribution of pharmaceuticals in the world. There may be shortages of these products due to unforeseen problems with the transportation along the supply lines such as raw material shipping, wholesaler- and retailer-based transportation delays. And the supplies of the drugs may also be temporarily curtailed due to manufacturing shutdowns or delays in the manufacturing process in countries facing COVID-19, although we have been hearing that in the generic industry, especially in India, there is decent stockpile of raw materials. Therefore, in the short term, we hope the manufacturing and supplies may not be a major concern.
Veronica Fowler (27:36):
Thanks, Jeff. Well, we've gone through many topics surrounding this coronavirus, including potential therapies, testing, governmental initiatives, and impacts to stakeholders in the pharmaceutical industry. And, of course, we'll continue to monitor the virus and the development of these and the stakeholder impacts as they unfold. Now for us here at IPD, we're all hunkered down and remotely working hard at keeping our subscribers informed, and any information that we're able to share will be provided on our infectious disease pages of our Payer and Provider Insights Portal, which provides pharmacy and therapeutic management support and drug information to payers, providers, and suppliers across the United States. Now, if you're not a current IPD subscriber, inquire about a subscription by emailing firstname.lastname@example.org. And any subsequent episodes will be posted to our LinkedIn page, so be sure to follow us there as well. Thank you for listening and stay healthy.
March 19th, 2020 Update
In order to shed light on this critical topic, IPD Analytics has made a publicly available podcast. Listen to IPD’s Executive Clinical Pharmacy Team discuss the most recent news on the coronavirus, including:
Clinical Development Pipeline and Trials
Pharmaceutical Industry Impacts