Acute respiratory distress syndrome (ARDS) can be brought on by COVID-19 and without any approved medication to treat it, patients can be put on a ventilator.

Cleveland, Ohio-based Athersys has developed its MultiStem cell therapy and is studying it for COVID-19 related ARDS. MultiStem is a regenerative candidate in clinical development that has shown the ability to promote tissue repair and healing in a variety of ways, such as through the production of therapeutic factors in response to signals of inflammation and tissue damage.

The therapy was recently given a Regenerative Medicine Advanced Therapy designation from the U.S. Food and Drug Administration (FDA) for ARDS. This allows sponsors to work closely with the FDA and receive their guidance on expediting development of their products.

Prior to this designation, Athersys had completed research exploring MultiStem for the treatment of pulmonary distress and recently completed an exploratory Phase 1/2 clinical trial for the treatment of ARDS.

They reported encouraging data from the study, and decided to also explore treatment for COVID-19.

As such, the company has initiated a phase 2/3 clinical trial evaluating MultiStem for the treatment of COVID-19 induced ARDS, which is now enrolling patients. The primary efficacy endpoint for the randomized, double-blind, placebo-controlled study will compare the number of ventilator-free days through day 28 among MultiStem and placebo treatment groups. 


Secondary objectives of the study are to evaluate 60-day all-cause mortality, time in the intensive care unit, pulmonary function, tolerability, and quality of life among survivors through one-year of follow-up. 

Athersys CEO Gil Van Bokkelen, PhD, and CFO Ivor Macleod, MBA, CPA about the investigative therapy and the company.

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Athersys has developed its MultiStem cell therapy for COVID-19 Acute respiratory distress syndrome (ARDS). Athersys CEO Gil Van Bokkelen, PhD, and CFO Ivor Macleod, recently spoke to Contagion providing background on the company and their MultiStem therapy.

Stem Cell Therapy for ARDS

An optimist may look at the difficulties surrounding vaccine hesitancy in the US and consider that, given the public’s investment of time and research into understanding 

, the eventual vaccine for the pandemic may be met with more acceptance than previous prophylaxes.

The outcome is a not certain one, but is one that clinicians like Bridget Calhoun, DrPH, MMS, would obviously hope for.

In the final segment of an interview with 

, Calhoun, Associate Dean for Academic Affairs and Research, and Chair and Associate Professor at Rangos School of Health Sciences at Duquesne University, discussed the need for people to learn parameters of vaccine development to better embrace the products.

She discussed how she and her peers are at benefit of being able to trust the development system implicitly, having seen the science that drives vaccines, knowing the oversight that’s required of any regulated product, and participating in the very clinical scrutinization of vaccines.

Calhoun also discussed the likelihood of COVID-19 vaccine risk-stratified prioritization, a strategy which will likely upset those who are not at significant risk of COVID-19 severity nor mortality, but would nonetheless want a vaccination as soon as possible. She noted how a similar situation during a flu vaccine shortage a decade ago led to such criticism.

Regardless of vaccination status in 2021 and beyond, people will still have a role of community protection to play for those at risk.

“There are some people who just can’t get the vaccine, whether they have had adverse reactions to vaccines in the past, or they have demonstrated an allergy to one of the components of the vaccine,” Calhoun said. “We have to be mindful of those folks, too.”

In consideration of the idea that the pandemic may lead to greater knowledge and adoption of preventive health measures.

Does COVID-19 Make a Better Case for Vaccines?

Just last week, the US Food and Drug Administration (FDA) launched an independent investigation into the safety data currently available for 

The adenovirus-based vaccine, being investigated by the company and the University of Oxford in phase 2/3 international trials, is among the leading candidates for potential FDA regulation and marketing for the prevention of the virus, pending late-stage efficacy and safety findings.

However, this new independent safety investigation is a continued stop from reports of a serious adverse event in a UK-based participant last month, and could greatly influence the FDA’s decision on marketing approval once an application is submitted.

Or, does this investigation serve another purpose?

, Bridget Calhoun, DrPH, MMS, Associate Dean for Academic Affairs and Research, and Chair and Associate Professor at Rangos School of Health Sciences at Duquesne University, discussed the appropriateness of the FDA’s decision to hit pause on the US-based trial arm for AZD1222—especially at a time of heightened scrutiny surrounding rapidly-progressing COVID-19 vaccine trials.

“Particularly in our democracy, we put a lot of faith in our national organizations,” Calhoun said. “So they have to be spot-on. They have to have reputable, responsible folks who are going to look at the data and make data-driven decisions based on the safety and efficacy of these vaccines.”

Calhoun added that public willingness and interest in a COVID-19 vaccine—a major factor in adopting a safe level of COVID-19 immunity—may be influenced by assuredness in vaccine research.

“And the way that we convince the general public to do that, and show them that it is in fact beneficial, is to know that it was scrutinized at every level,” she said.

Perspective on the ongoing independent safety reviews for one of the more promising vaccine candidates.

What to Make of the AstraZeneca COVID-19 Vaccine Trial Stalls

In recent months, convalescent plasma for the treatment of 

 has seen its share of news and public debate within the medical science community and beyond. 

In August, clinicians at Houston Methodist 

that transfusing critically ill COVID-19 patients with high antibody plasma early in their illness—within 72 hours after hospitalization proving most effective&mdash;reduced the mortality rate.

They transfused 316 patients, and a preliminary analysis showed a significant reduction (P = 0.047) in mortality within 28 days, specifically in patients transfused with an anti-spike protein receptor binding domain titer of ≥1:1350 within 72 hours of their admission with plasma.

Of the 316 transfused patients, 136 met a 28-day outcome and were matched to 251 non-transfused control COVID-19 patients.

During that same month, the US Food and Drug Administration (FDA) 

 an Emergency Use Authorization (EUA) for convalescent plasma in treating COVID-19. However, the FDA came under scrutiny when the agency reported a 35% lesser mortality rate for patients taking convalescent plasma. FDA Commissioner Steve Hahn, MD, took responsibility for the information and walked back the statistic after there was an outcry from the medical community.

Historically, convalescent plasma has been used for infectious disease treatment for over 100 years, and there are ongoing trials right now looking at the therapy for COVID-19. In late September, the National Institutes of Health (NIH) decided to expand 2 existing trials. These are randomized, placebo-controlled clinical trials to evaluate further convalescent plasma for hospitalized COVID-19 patients.

"The evidence on convalescent plasma as a treatment for severe cases of COVID-19 is promising but incomplete. We need to carry out rigorous randomized control clinical trials to determine how this therapy can improve outcomes," said Francis Collins, MD, PhD, director, NIH. "While the world waits for an effective vaccine, it is vital that we simultaneously expand the options for available treatments for those currently suffering from the worst effects of this disease."

The trials are receiving $48 million in support through Operation Warp Speed. Within NIH is the National Center for Advancing Translational Sciences (NCATS), and they will oversee the grant awards through its Clinical and Translational Science Awards (CTSA) Program research network. The CTSA's Trial Innovation Network (TIN) will play a key role in working to add study sites and enroll patients, including those from communities disproportionately affected by COVID-19.

Christopher Austin, MD, director, NCATS, says the center was developed to solve the problem of getting devices, diagnostics, and therapies to patients. They are involved in the “scientific and operational” aspects of translational research.

 recently about the organization’s mission and the specifics of the 2 expanded trials for convalescent plasma.

Within NIH is the National Center for Advancing Translational Sciences (NCATS) and they will oversee the grant awards. Christopher Austin, MD, director, NCATS, discusses the specifics of the 2 trials being expanded.
 

NIH: Expanding Trials for Convalescent Plasma

Guidance from the US Centers for Disease Control and Prevention (CDC) came under scrutiny last month when reports showed dissent between federal leadership-pushed language on 

 transmission and testing parameters, and the members of the CDC who emphasized science-informed measures.

What eventually manifested was a series of amended and removed guidances on the CDC’s website, the most recent of which weighed in on the topic of SARS-CoV-2 aerosol versus droplet transmission risk debate.

Last week, Anthony Fauci, MD, director of the National Institutes of Allergy and Infectious Diseases (NIAID), 

, a respiratory health podcast series from sister publication 

 and the American Lung Association (ALA).

On the topic of the CDC’s varying messages, Fauci admitted he wasn’t sure of where the agency stood.

“I just know it is likely that there is some degree of aerosol transmission,” he said. “I don’t know to what extent it is responsible for transmissions.”

Fauci also provided perspective on the current state of transmission risk in community gatherings including college campuses, suggesting a strategy of minimal-risk infection management that would allow for classes and programs to continue (mostly) unaffected.

 “The perfect scenario would be that if a college had the capability, when a student got infected—and students will get infected&mdash;they had the capability of putting them on a separate floor of a dorm, or in a completely separate dorm, where they could comfortably recover, because most of the time they’re going to be very sick,” he said.

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Fauci also shares suggestions for college campus to mitigate community-based spread while classes continue.

Anthony Fauci, MD: How SARS-CoV-2 Is Most Likely Spread

As leading vaccine developers continue to collect phase 3 data for 

 candidates, focus is beginning to turn from clinical effectiveness and safety toward vaccine prioritization and distribution.

How will the first regulated COVID-19 vaccines be managed and distributed?

, Lorne Clancey, senior director of temperature and environmental monitoring solutions at CenTrak, discussed an interesting facet of COVID-19 vaccine strategies: required storage temperatures for leading candidates.

“Some are going to require extreme cold—ultra-low temperatures, as a matter in fact, about minus-80 (Fahrenheit),” he said. “They have to be kept at this temperature to provide the necessary inoculation strength it has to deliver.”

Promising vaccines including the quartet of mRNA-based candidates from Pfizer and BioNTech would require dry ice use for storage and transportation, and space- and energy-consuming ultra-low units in hospitals and physician’s offices.

More is riding on the scientific community’s ability to cater to these specific needs than is discussed relative to the clinical data of the vaccines themselves.

“If the vaccine is compromised because of temperature, it’s not going to deliver the anticipated outcome, and that would basically mean the patient would have to come back and get it again,” Clancey said.

A discussion with an expert on the particularities of the vaccines, which vary in temperature climate requirements and dosages.

How Will COVID-19 Vaccines Be Distributed and Stored?

 candidates are nearing the stage in which real-world phase 3 data will become available for public consumption and regulatory consideration.

Speculation as to when the first designed prophylaxes will become available have varied from anytime soon to mid-2021—but in just 7 months of research and development, COVID-19 vaccines have become a likelihood.

Of course, understanding surrounding vaccine effectiveness and safety is still under development with the agents themselves.

This week, Anthony Fauci, MD, director of the National Institutes of Allergy and Infectious Diseases (NIAID), 

Fauci discussed his belief on how prioritization of differing vaccines may look once multiple options are available. He also discussed the 

 surrounding a serious adverse event in the phase 3 international trial for AZD-1222, the adenovirus-based candidate from AstraZeneca and Oxford University which is currently under independent safety review.

Such a situation, which is common in nearly every vaccine development trial, Fauci said, is looked at with great scrutiny for a vaccine that would be potentially administered to millions after just months of assessment.

He argued against the notion that the trial pause is indicative of an unsafe agent; rather, he said, it’s proof of a careful assessment system that is not compromised by the expediency of the trial itself.

“This shows the system actually works, because when you do have a serious adverse event, the system allows you to immediately pick it up, put on a pause, examine what went on before you make a decision to proceed,” Fauci told 

. “It actually gives you comfort that the system is working, as opposed to you’re doing something that is inherently unsafe.”

Why the AstraZeneca & Oxford University trial's pause due to an adverse event was a sign to Fauci the vaccine monitoring systems are working.

Anthony Fauci, MD: COVID-19 Vaccine Understanding is Developing

One of the most interesting aspects of the COVID-19 pandemic has been the pace of medical innovation. New therapies, investigative vaccines, and devices are all being developed at an unprecedented speed. Entrepreneurial companies have found their way into the market and bring unique ideas.

San Diego, Calif.,-based Aethlon Medical is one such company. They have developed their proprietary Hemopurifier, which is a therapeutic device designed for the single use depletion of circulating viruses.

“The Hemopurifier is an extracorporeal cartridge meaning that it filters blood outside the body similar to a dialysis cartridge,” Tim Rodell, MD, Chief Executive Officer of Aethlon, said.

Aethlon is studying its Hemopurifier in viral diseases under an open Investigational Device Exemption from the US Food and Drug Administration (FDA). With an approved supplement from the FDA, Aethlon is going to start a new feasibility study to treat COVID-19 patients with the Hemopurifier.

The Hemopurifier has previously been tested in patients with hepatitis C virus (HCV) infection and in one patient with Ebola virus infection. A laboratory version of the Hemopurifier has also been shown to clear multiple other viruses 

 including a model version of the Middle Eastern Respiratory Syndrome (MERS) virus which is a coronavirus from the same family as the SARS-CoV-2.

The feasibility study, which is the device equivalent of a phase 1 trial, will enroll up to 40 subjects at up to 20 centers in the US. Participants for the study will have established laboratory diagnosis of COVID-19, be admitted to an intensive care unit (ICU), and will have acute lung injury and/or severe or life-threatening disease among other criteria.

 recently spoke to Rodell about the device and provided an update on the feasibility study.

Aethlon Medical is developing its proprietary Hemopurifier, which is a therapeutic device designed for the single use depletion of circulating viruses.

Innovative Device Looks to Filter Viruses

The topic of US healthcare coverage is gaining steam in recent weeks for no fewer than 3 circumstances occurring all at once: the Presidential election this November, the pending nomination of a new Supreme Court justice, and of course, the ongoing 

Opinions vary on the US’ role in providing healthcare insurance options to citizens, and much scrutiny has been raised by clinicians and experts on the totality of healthcare spending relative to actual patient outcomes in the US. While the ideas of retention versus amendment have long-term implications, today’s perspective is focused on the recent issues presented by COVID-19.

, Brad Spellberg, MD, chief medical officer of the Los Angeles County and University of Southern California Medical Center, shared his personal concerns with discussion around potentially amending or removing the Affordable Care Act (ACA). By his count, its removal could result in a national uninsured rate increase of nearly 70%.

“In the middle of a global pandemic is not the time to be removing healthcare access for people,” Spellberg said.

Removing access for that many Americans could compromise their access to, or interest in, COVID-19 testing, he explained. From there, they could be susceptible to worsened outcomes with virus and a greater risk of transmitting the virus in their community.

Spellberg also touched on the vitality of a healthcare “safety net” like ACA for the same US population that generally comprises the “essential worker” population during COVID-19. In his eyes, a major reform would detriment the country’s public health and economic status further.

“The more we strip healthcare access away from these people, the more the pandemic will be fed, the more cases will spike, the more the economy will suffer,” he said.

Brad Spellberg, MD, emphasizes his belief the Affordable Care Act needs to be retained so as long as the pandemic persists.

An Infectious Disease Expert Argues for ACA During COVID-19

Inflammation in the organs caused by COVID-19 has been a significant problem for patients and can lead to a worsening of their conditions and in some cases lead to death. One particular area  that has been problematic with severe cases of COVID-19 has been the blood vessels within the lungs.

A new phase 2 clinical trial using razuprotafib, an investigational therapy, activates a key pathway for stabilizing blood vessels in the lungs. Razuprotafib may also prevent and treat respiratory distress in COVID-19 patients. 

The University of Cincinnati Heart, Lung and Vascular Institute is one of the sites across the United States selected for a randomized, double-blind and placebo-controlled phase 2 study. As part of that trial, which is designed as a parallel-group, dose escalation and proof-of-concept study, razuprotafib will be administered 3 times daily for a 7-day period to hospitalized patients. The trial may enroll approximately 180 patients nationwide.

The investigational therapy activates Tie2 receptor proteins on the surface of endothelial cells to bind to angiopoietins to support endothelial viability and function and are needed to form, repair and stabilize blood vessels.

Principal investigator Richard Becker, MD, director of the University of Cincinnati Heart, Lung and Vascular Institute spoke to 

 about the investigational therapy and the parameters of the phase 2 clinical trial.

Principal investigator Richard Becker, MD, director of the University of Cincinnati Heart, Lung and Vascular Institute discusses the phase 2 clinical trial for razuprotafib.