The COVID-19 pandemic is putting the global healthcare system to the test. During this unprecedented time, the University of Arizona College of Pharmacy is working to make a difference with leading-edge science pushing the boundaries of innovation and discovery, and training highly skilled practitioners to enter the fight.
“A Starting Point”
“Each one of us has to ask ourselves, ‘What can we do to make a difference?’” shared Jun Wang, PhD, assistant professor for the College of Pharmacy.
Dr. Wang has been studying respiratory viruses, including influenza, in his laboratory for several years. With the rise of COVID-19, his experience with antivirals allowed him to quickly transition some of his ideas and laboratory resources to focus on new projects related to the pandemic. Within a period of two months, breakneck speed in the timeline of academic research, his lab was able to identify several promising drug candidates that inhibit SARS-CoV-2 virus in cell culture.
“Everything has a starting point and we’re here to provide that starting point,” explained Dr. Wang. “What we discover may or may not be a drug, but we can identify chemicals that result in a drug. Pharmaceutical companies can then take over and continue the drug development work.”
The pharmaceutical industry has undergone significant changes in the way it operates over the past twenty years, and these changes have opened up new avenues for academic research. Early drug discovery is now being shifted from companies to academic institutions and researchers like Dr. Wang.
In recent years, an increasing number of alliances and licensing deals have occurred between academia and the industry. When Pfizer Inc., a multinational pharmaceutical corporation, came looking for a partner to test a series of compounds against SARS-CoV-2, the pathogen that causes COVID-19, they turned to the National Institute of Health’s (NIH) database of researchers. Dr. Wang, whose lab is currently funded in part through a grant from the NIH, was identified as the right person for the job.
“All the big pharmaceutical companies and the NIH are trying to come up with a solution,” said Dr. Wang. “[Pfizer] has a number of candidate molecules which they think might be active against SARS-COV-2, but they don’t have any biochemical assays set up to test their hypothesis. Through the introduction of NIH program officers, they came to know that my laboratory has developed those assays and approached us to test their molecules.”
Other academic researchers throughout the country are also finding ways to assist in the effort to develop a treatment. For years Chris Hulme, PhD, a professor in the college, has been working to identify novel treatments for Alzheimer’s Disease. In recent weeks he has shifted his efforts towards COVID-19 research.
“There remains a significant knowledge gap in the precise pharmacological underpinnings of COVID-19. As such, fundamental studies of signaling mechanisms involved in disease progression are required, which is typically the strength of academic research,” explained Dr. Hulme. “The deliverables of such efforts should unveil new biological targets which medicinal chemists would be able to engage to deliver therapeutics that are small molecules and orally bioavailable. Efforts are also continuing to repurpose safe, existing drugs, which is heavily driven by academic researchers. In short, there is a broad spectrum of activities that academic researchers can impactfully engage to address this insidious pandemic.”
Jutta Wanner, PhD, is the co-director of the Arizona Center for Drug Discovery housed within the college.
“The good thing about a university setting is that people truly work collaboratively,” shared Dr. Wanner whose extensive professional experience in the pharmaceutical industry includes positions at Roche, Lilly Forschung, and BlinkBio. “From a chemistry perspective, you can tackle any disease because medicinal chemists are disease agnostic.”
Facilitated by partnerships with academic drug discovery researchers, the pharmaceutical industry is testing different approaches to clear the virus. By the end of April, there were more than 200 clinical trials for COVID-19 registered in the U.S alone. The timeline for drug development is notoriously lengthy and the process is research intensive; however, regulatory agencies are permitting accelerated measures to help speed the development of medications. The U.S. FDA, European EMCDDA, and Chinese CDE are all using special emergency clinical trial approval processes for COVID-19 and a number of products are already moving through the systems.
“Where the timelines have been shortened are with companies that already had an antiviral drug in their pipeline for another disease,” explained Dr. Wanner. “Gilead’s drug remdesivir comes to mind. All the preclinical de-risking for this compound had been done and safety had been established in humans.”
Bench to Bedside
“Right now, it feels like we’re in the calm before the storm,” shared Christopher Edwards, PharmD, assistant professor at the college and clinical pharmacy specialist in emergency medicine at Banner - University Medical Center Tucson.
Hospital emergency departments are often the first stop for a COVID-positive patient. As cases continue to grow, having a clinical pharmacists like Dr. Edwards on your healthcare team is more important than ever.
“We’re here to make sure that during a challenging situation, good therapeutic decisions are being made.” explained Dr. Edwards.
The medication use-process follows a straightforward path in a hospital. The patient’s healthcare team reviews his or her status, sets appropriate goals, and then creates a therapeutic plan. Medications that are part of these therapeutic plans are ordered through the hospital pharmacy where they are reviewed for accuracy, and then dispensed by a team of pharmacists. In an emergency department, when situations evolve rapidly, the system of checks and balances can break down.
“That’s where mistakes get made,” said Dr. Edwards. “In those situations, there is a lot of high energy and high stress, and having one person who is focused on the medication helps reduce the potential for errors.”
In the era of COVID-19, healthcare workers are dependent on data collected through clinical trials to understand what immediate treatment options are available. Trained as medication experts, Dr. Edwards and the team of other clinical pharmacists have spent the past several weeks evaluating literature to provide guidance on what drugs may be considered an effective treatment, and what may need more scrutiny. “
The challenging thing is to not get too excited or to suspend rigorous scientific methodology because something looks like it might be good,” said Dr. Edwards. “The initial study that got the most attention looking at hydroxychloroquine and azithromycin only included 6 patients that received that medication combination and while it did look promising, it didn’t look at any clinical endpoints.”
The study by a French-based researcher and his colleagues examined the use of the anti-malarial drug hydroxychloroquine in combination with the antibiotic azithromycin in a small number of COVID-19 patients. They received criticism from scientists and public health officials for issues including confounders, a lack of randomization, and reported data that did not match the plan outlined in a clinical trial registry. Another preprinted paper by the same group of researchers similarly received criticism for a lack of control group, the inclusion of asymptomatic carriers, and questionable results.
“Clinical pharmacists were able to quickly evaluate the quality of available evidence, determine how we should utilize our limited supply of hydroxychloroquine, and what kinds of patients should get it, if any,” explained Dr. Edwards. “We developed criteria for use within a day of that study being published to make sure that we weren’t frivolously using this potentially dangerous treatment based on flimsy data.”
As the world waits for a cure, healthcare teams are able to offer their critically ill COVID-19 patients supportive care to treat symptoms. “These patients will likely be in severe respiratory distress. They may need a ventilator and that process requires a lot of medication use, especially if the patient is unstable,” says Dr. Edwards. “We can make sure that the drugs the physicians are using are correct for those patients, that they are dosed effectively, and make sure they are readily available.”
Embedded in the Community
Behind the counter of a local community pharmacy, Theresa Taylor, PharmD, alumna of the College of Pharmacy class of 1992 is wiping down every surface she and her team have touched.
“Pharmacies tend to have regular sanitizing procedures,” explained Dr. Taylor. “Now our efforts are heightened and intentional. I set my phone alarm to ring every 30 minutes to signal staff to wash hands and sanitize.”
Due to aggressive retail practices, approximately 67,000 pharmacies are open across the U.S., conspicuously placed on most city street corners or set within grocery and department stores. More than 90% of U.S. residents nationwide live within 5 miles of a community pharmacy, and in rural and medically underserved communities, pharmacists are often the only healthcare provider that is immediately accessible to patients.
“You can walk into a pharmacy at any time, and ask anything you wish without an appointment or being charged a fee,” said Nancy Alvarez, PharmD, associate dean of academic and professional affairs at the college for the Phoenix campus. “There is no other health professional that does that.”
In the U.S. there are an estimated 13 billion pharmacy visits each year. Frequent interaction with the general public has placed community pharmacists at the center of public health initiatives, including vaccinations, and more recently the risks associated with e-cigarettes and vaping. In the midst of the current crisis, many of Dr. Taylor’s patients are turning to her for advice beyond just their medication.
“I have received many calls since the start of this current situation from patients seeking my opinion on what they are hearing in the media,” said Dr. Taylor “I advise people on the resources available in their community and triage to other sources of support.”
Much of her day-to-day involves interacting with physicians and other primary care providers to advise on medication use and alternatives when a patient’s needs aren’t being met. In the past weeks, the added attention put on hydroxychloroquine and azithromycin has caused shortages in areas across the country. For patients who rely on these medications, their local pharmacist may be the best advocate they have to work with physicians to identify alternatives.
In April, the U.S. Department of Health and Human Services issued a statement authorizing licensed pharmacists to order and administer FDA-authorized COVID-19 tests. Pharmacists had already seen significant success in increasing access to vital health care services like vaccines following the authority to administer vaccinations over 20 years ago. This new guidance, issued under the Public Readiness and Emergency Preparedness Act, will expand testing capabilities in pharmacies, including some in Arizona, are mobilizing to meet the needs of communities, and support other front-line healthcare professionals.
Making a Difference
“What is the motivation for us to come to work?” asks Dr. Wang. “Spending eight to ten hours a day, six to seven days a week in the lab? For me, the motivation is, ‘Can we make a difference?’”
During this uncertain time, pharmacists across the globe are critically important to helping the public remain safe, healthy, and informed. Their expertise in medication plays an increasingly important role in our healthcare systems and pharmaceutical researchers are on the forefront of drug discovery research with the hopes of finding a cure. They’re making a difference every day whether from behind a counter, at the bedside, or in the lab.