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The trials and tribulations of COVID-19
The trials and tribulations of COVID-19
A selection of five articles from our May 2020 issue of DDNews on challenges to clinical trials in the face of a global pandemic, solutions to help...and a couple companies looking to get to clinical trials soon with COVID-19 therapeutics
To view the May issue online (as a PDF file) or download it, click here.
The FDA, trials and the coronavirus
COVID-19 causes agency to issue guidance for conducting clinical trials
SILVER SPRING, Md.—There is absolutely no surprise that the U.S. Food and Drug Administration would issue guidelines or have some commentary regarding clinical trials during the COVID-19 pandemic, but in case you missed it when it went around the first time, read on.
Message from FDA
The U.S. Food and Drug Administration [has] issued a guidance for industry, investigators and institutional review boards conducting clinical trials during the coronavirus (COVID-19) pandemic.
The FDA recognizes that the COVID-19 pandemic may impact the conduct of clinical trials of medical products, including drugs, devices and biological products. Challenges may arise, for example, from quarantines, site closures, travel limitations, interruptions to the supply chain for the investigational product, or other considerations if site personnel or trial subjects become infected with SARS-CoV-2, the virus that causes COVID-19. These challenges may lead to difficulties in conducting the clinical trials. The FDA is aware that protocol modifications may be required, and that there may be unavoidable protocol deviations due to COVID-19. Although the impact of COVID-19 on trials will vary depending on many factors, including the nature of disease under study, the trial design and in what region(s) the study is being conducted, the FDA outlines considerations to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice and minimizing risks to trial integrity. Considerations recommended include, among others, sponsors evaluating alternative methods for assessments, like phone contacts or virtual visits, and offering additional safety monitoring for those trial participants who may no longer have access to investigational product or the investigational site.
“With this guidance issued today, the FDA is helping industry and investigators navigate the COVID-19 pandemic and help assess how to move forward with critical clinical trials,” said Dr. Anand Shah, FDA deputy commissioner for medical and scientific affairs. “The FDA released this guidance to emphasize that at all times, patients’ safety should continue to be at the forefront of considerations. We want to support the continuance of these clinical trials in compliance with good clinical practice and minimizing risks to trial integrity, while also safeguarding the health and well-being of study participants.”
Social distancing meets clinical trials
PPD subsidiary and Science 37 to provide virtual trial access to patients globally
HORSHAM, Pa. & LOS ANGELES—Remote clinical trials didn’t start with the current global pandemic, though the interest for them is certainly growing fast as many studies face delays or the risk of cancellation due to social distancing and concerns over patient and researcher safety.
In that vein, early April saw PPD Inc. subsidiary Accelerated Enrollment Solutions (AES) and virtual clinical trials company Science 37 announce that they will collaborate to recruit and enroll clinical trial participants who live beyond the geographic location of traditional research sites—and they will work to rapidly deliver continuity solutions for clinical trials affected by COVID-19, including the use of telehealth to remotely screen patients and conduct study visits.
The collaboration enables AES to provide its customers with increased patient access by reaching beyond its existing physical site infrastructure of more than 180 research sites. These patients can instead participate in AES studies through Science 37’s Metasite, a hybrid clinical trial methodology that combines traditional site visits with remote trial capabilities, allowing patients located virtually anywhere to participate in a clinical trial. The collaboration also enables Science 37 to extend its investigator network by leveraging AES’ global research network. In total, the collaboration offers multiple combinations of traditional and virtual visits for conducting highly patient-centric trials around the world.
“We are pleased to provide our customers, through our collaboration with Science 37, one of the most advanced, trial-tested approaches to clinical research virtualization,” said Roger Smith, general manager of AES. “By offering the Science 37 Metasite in conjunction with our existing network, we give our customers a taste of the future, while more patients will have the opportunity to participate in trials that might otherwise be unavailable due to location restrictions.”
In addition to managing its global research sites, AES coordinates startup, patient enrollment and study conduct under a single contract via centralized and controlled processes. Concurrently, Science 37 oversees an extensive network of telemedicine investigators, in-home nurses and clinical research coordinators who are connected by a purpose-built, integrated platform to orchestrate virtual trials, also known as decentralized clinical trials.
“Science 37 is already renowned for our ability to conduct fully decentralized trials in the United States,” stated David Coman, CEO of Science 37. “Now, by combining with the extensive global reach of AES, we are building on our promise to ‘make virtual the new reality’ nearly anywhere in the world.”
Of course, Science 37 isn’t alone in the market, and Pleasanton, Calif.-based Veeva Systems debuted its own personal spin on the “distancing” aspect of clinical trials in April when it announced new remote monitoring capabilities in Veeva SiteVault Free for source document review and verification in clinical trials.
“Remote monitoring supports the immediate need for sites and study monitors to continue working together while onsite visits have largely stopped,” remarked Bree Burks, vice president of site strategy at Veeva and a former clinical research director. “Veeva SiteVault Free gives sites access to remote monitoring capabilities, at no cost, so they can keep running studies and treating patients.”
SiteVault Free allows sites, sponsors and CROs to remotely manage and track the workflow and downstream processes for source document review and verification. Sites and study monitors can easily view, comment and respond to questions in a single centralized system. Reporting, dashboards and automatic notifications enable stakeholders to organize their tasks, get complete visibility into documents, and prioritize activities for immediate action.
And in a little hint that companies might want to consider the idea of remote trials at least in passing—even once the pandemic is long over—there is this commentary from data and analytics company GlobalData: “There has been an overall increase in clinical trials that have pushed back their estimated start dates since the beginning of January 2020, largely due to the COVID-19 pandemic. However, remote studies such as Heartline may have a significant advantage, as patients can continue to enroll and participate from their homes.”
As such, the Heartline trial will likely continue with minimal disruptions, predicts GlobalData. Of course, a major point of the Heartline Study—being conducted by Johnson & Johnson and Apple Inc.—was to be remote, as it aims to evaluate changes in stroke risk and atrial fibrillation detection through the use of the Heartline Study’s app and the Apple Watch.
As such, Heartline’s relatively rosy position in the current clinical trial climate was happenstance rather than design. But there might be lessons to take away, as associate pharma analyst Kajal Jaddoo of GlobalData pointed out in April that “Across various indications, clinical trials are increasingly expected to experience delays as investigators and hospitals, which are used as clinical trial sites, are inundated with COVID-19 patients. With fewer trial sites and investigators available to run the trials, clinical trials for certain indications will be deprioritized.”
Global COVID-19 trial tracker launched by Cytel
CAMBRIDGE, Mass.—Cytel Inc. has launched the open-access global COVID-19 Clinical Trial Tracker to help facilitate greater collaboration between researchers, policymakers, clinicians, journalists, philanthropists and other critical stakeholders who need to understand the complex dynamics of the global response to finding a solution to the COVID-19 outbreak.
In particular, this tool is designed to enable them to make more informed and pragmatic decisions on how to channel scarce resources. As the company noted, clinicians and local government need to know what trials are taking place in their community to ensure that the right patients receive the right exploratory treatment, while philanthropists and national policymakers “deserve a one-stop shop to determine which are the most promising early-phase treatment results.”
"While much of the world is isolating, the scientific and clinical communities are coming together to fight the COVID-19 virus. United by an unprecedented sense of urgency, there is a level of collaboration that we’ve not seen before, and, despite the current pressures on the healthcare system, hundreds of hospitals are still committed to working on clinical trials,” said Joshua Schultz, CEO of Cytel. “At Cytel, we have been supporting numerous clients in developing statistically rigorous models for fast data analysis and addressing the various challenges the pandemic presents in the current clinical environment. We are committed to supporting the global effort—and launching the COVID-19 Clinical Trial Tracker offered an additional way to do that."
The tracker project is funded in part by The Bill and Melinda Gates Foundation.
GSK and Vir team up to fight coronaviruses
LONDON & SAN FRANCISCO—GlaxoSmithKline plc (GSK) and Vir Biotechnology Inc. announced in April that they have signed a binding agreement to enter into a collaboration to research and develop solutions for coronaviruses, including SARS-CoV-2, the virus that causes COVID-19.
The collaboration will use Vir’s proprietary monoclonal antibody platform technology to accelerate existing and identify new antiviral antibodies that could be used as therapeutic or preventative options to help address the current COVID-19 pandemic and future outbreaks. The companies will leverage GSK’s proficiency in functional genomics and combine their capabilities in CRISPR screening and artificial intelligence to identify anti-coronavirus compounds that target cellular host genes. They will also apply their combined expertise to research SARS-CoV-2 and other coronavirus vaccines.
“Vir’s unique antibody platform has precedented success in identifying and developing antibodies as treatments for multiple pathogens, and it is highly complementary with our R&D approach to focus on the science of immunology,” said Dr. Hal Barron, chief scientific officer and president of R&D for GSK. “I am very excited that the talent and passion of our two companies will come together to develop solutions for multiple diseases, including the very promising antibody candidates targeting COVID-19.”
Because of the urgent patient need for COVID-19 solutions, the initial focus of the collaboration will be to accelerate the development of specific antibody candidates identified by the Vir platform, VIR-7831 and VIR-7832, that have demonstrated high affinity for the SARS-CoV-2 spike protein and are highly potent in neutralizing SARS-CoV-2 in live virus-cellular assays. Subject to regulatory review, the companies plan to proceed directly into a Phase 2 clinical trial within the next three to five months.
The companies have also agreed to conduct research into SARS-CoV-2 and other coronavirus vaccines by coupling GSK’s vaccines technologies and experience with Vir’s ability to identify neutralizing epitopes that are present across entire viral families.
“It is becoming increasingly clear that multiple therapeutic approaches, used in combination or in sequence, will be necessary to stop this coronavirus pandemic. It is likely that the current coronavirus outbreak will not be the last,” noted Dr. George Scangos, CEO of Vir Biotechnology.
In addition, to gain access to Vir’s technology, GSK will make an equity investment in Vir of $250 million.
Analysts at Leerink Partners said of the deal: “Previously, GSK announced collaboration plans with University of Queensland and the Coalition for Epidemic Preparedness Innovations, Clover Biopharmaceuticals, and more recently Xiamen Innovax, although GSK’s efforts were limited to making its adjuvant system available. GSK is one of the largest antiviral drug companies in the world and a major vaccine manufacturer, and we believe this collaboration shows GSK’s willingness to take more responsibility for deploying its internal capabilities and capital against this global pandemic, which should generate goodwill for both the company and the industry.”
Stemming the threat of ARDS
Citius signs exclusive option with Novellus to license novel stem cell therapy for acute respiratory distress syndrome
CRANFORD, N.J. & CAMBRIDGE, Mass.—Citius Pharmaceuticals Inc., a specialty pharmaceutical company focused on developing and commercializing critical-care drug products, recently signed an exclusive six-month option agreement to in-license a stem cell therapy for acute respiratory distress syndrome (ARDS) from a subsidiary of preclinical-stage biotechnology company Novellus Inc.
Novellus’ patented process uses its exclusive non-immunogenic synthetic messenger ribonucleic acid (mRNA) molecules to create induced pluripotent stem cells (iPSCs) that, in turn, generate mesenchymal stem cells (MSCs) with what the companies say are “superior immunomodulatory properties.” They add that MSCs have been shown to be safe in more than 900 clinical trials and to be effective in treating a number of inflammatory diseases, including ARDS.
“ARDS is the most common cause of respiratory failure and mortality in COVID-19 patients. Currently, there is no proven treatment for ARDS. Literature supports the use of counter-inflammatory MSCs for ARDS, and papers published in China have shown that at least seven COVID-19 patients with ARDS responded to MSC therapy,” said Citius CEO Myron Holubiak. “Clearly this is an avenue that shows promise and should be pursued as a potential treatment for ARDS. We believe Novellus is at the forefront of creating allogeneic, iPSC-derived MSCs. These cells have the potential to overcome the limitations of MSCs derived from adult donors, which are telomere shortened and introduce variability into the manufacturing process.”
Added Novellus Chief Science Officer Dr. Matt Angel: “Using our mRNA-based cell-reprogramming technology, Novellus can provide a near-unlimited supply of MSCs for treating patients with ARDS, including those critically ill from COVID-19. These will be allogeneic (“off-the-shelf”) cells that in vitro have demonstrated much greater expansion potential and much higher immunomodulatory protein expression than donor-derived MSCs. We are excited to employ our technology to such an urgent medical crisis, and believe that our MSCs represent an ideal source of cells to be used in this extremely important development effort.”
ARDS is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. This rapidly progressive disease occurs in critically ill patients, most notably now in those diagnosed with COVID-19. ARDS affects approximately 200,000 patients per year in the United States, exclusive of the current COVID-19 pandemic, and has a 30- to 50-percent mortality rate. It is sometimes initially diagnosed as pneumonia or pulmonary edema.
“No effective pharmacotherapy for ARDS exists, and ARDS-related morbidity and mortality are high,” Holubiak added. “MSCs have been studied in the treatment of lung injury, and we aim to build upon this work with Novellus’s iPSC-derived MSCs to improve the immunomodulatory response in humans. We have assembled a team of experts who are dedicated to advancing this project to an Investigational New Drug application as quickly as possible.”