The University of Wisconsin has been selected by Regeneron for the Phase 3 clinical trial evaluating REGN-COV2, the advanced investigational monoclonal antibody designed to destroy SARS-CoV-2, the virus behind COVID-19. This novel investigational product has been expedited via a not well known process, in collaboration with the U.S. Food and Drug Administration (FDA), involving a so-called sentinel population. Developed by New York-based Regeneron, the drug is essentially an “antibody cocktail” derived from the combination of antibodies of recovered COVID-19 patients and humanized mice. UW Health expects to enroll between 90 and 150 COVID-19 patients in the Phase 3 clinical trial involving those who don’t actually have the disease but have been exposed via a family member or housemate. REG-COV2, if safe and effective, could absolutely transform COVID-19 care. And Regeneron has pressure in the form of at least $610 million in public funds allocated via Operation Warp Speed.
The Most Promising Treatment?
David Wahlberg with the Wisconsin State Journal recently reported that REGN-COV2 drug maker Regeneron received $450 million from the Trump Administration’s Operation Warp Speed on top of the $160 million already given to support the clinical trials process. Dr. Francis Collins, director of the National institutes of Health, recently commented that this could be the most promising of the therapeutic candidates for COVID-19.
Collins told members in the Senate earlier this month at a hearing ,“If I had to pick one, I think the monoclonal antibody cocktails have a lot going for them.” She continued, “There’s all kinds of reasons to think this is the kind of virus it should work for.”
Regeneron could completely shake up the COVID-19 treatment space should this product be safe and effective. They have committed to give a certain amount of product away free. TrialSIte has some questions about how this study was so rapidly progressed to Phase 3. An open and helpful spokesperson at Regeneron explained what they could publicly disclose about the FDA and company’ agreement to allow for a sentinel population model to assess preliminary safety. An independent drug monitoring committee gave the greenlight to progress while Regeneron was still blinded to the data of those that were first treated with REGN-COV2. But TrialSite will be closely monitoring REGN-COV-2.
UW is one of around 100 clinical investigational sites involved in three clinical trials investigating REGN-COV2. As TrialSite News reported, the three studies include one for hospitalized patients, another for patients infected but not in the hospital and a third dealing with individuals who are not ill but have been possibly exposed via a family member or someone living in the house with them. It is this third study that UW will support. The hypothesis: can REGN-COV2 stave off infection in those who are not infected necessarily but who reside with someone who recently was infected with SARS-CoV-2.
Experienced Principal Investigator
Leading the charge for UW-Madison is Dr. William Hartmann, a UW Health anesthesiologist. Dr. Hartman is no stranger to COVID-19 trials as he served as Principal Investigator to a UW COVID-19 convalescent plasma trial. Back in April, Dr. Hartman led the effort and, according to the UW Health news, “worked around the clock to start this clinical trial, an effort that takes months.” Dr. Hartman commented, “The goal (of the third study) is to give them the antibody so that hopefully they don’t develop COVID.”
As Dr. Hartman led the convalescent plasma study at UW Health, it made sense to tap into his expertise, experience, and importantly wisdom for this study of a drug that at least in part, is based on a similar approach. Before proceeding to a review of investigational product, we provide a brief review of UW’s experience with COVID-19 antibodies via the convalescent plasma study.
UW Health—Significant Experience with COVID-19 Convalescent Plasma
UW Health conducted a study targeting the use of convalescent plasma on COVID-19 patients. According to Dr. Hartman and as reported by the Wisconsin State Journal, the plasma treatment exhibited some promise as a treatment. The prominent academic medical center tested convalescent plasma as a COVID-19 therapy on 40 patients infected with SARS-CoV-2. The university reports most of these patients are well.
Of the first 31 patients studied, 16 had severe cases of COVID-19 while 15 of the patients were classified as having a serious life-threatening case of COVID-19. Four of those in the study with life-threatening COVID-19 died. Among those with a severe classification, all but one avoided the need for intensive care and ventilation. Moreover, Harman reported that the study team observed that COVID-19 patients in the study required less medical support a week after convalescent plasma transfusion. The results were recently uploaded to the preprint server medRxiv. These findings haven’t been peer reviewed as of yet. Harman reported to the local news that the large national convalescent plasma study will be published soon.
The Investigational Product
Regeneron’s REGN-COV2 is based on the antibodies derived from recovered COVID-19 patients as well as a sophisticated process involving humanized mice. Known as convalescent plasma, the idea is that health providers collect the antibodies (immune system proteins) that serve the purpose of fighting infection from the plasma of those individuals who have fully recovered from COVID-19. In a convalescent plasma scenario, the donor’s antibodies are used up as the treatment is administered to an ill patient.
In the case of REGN-COV2, Regeneron employed many scientists to evaluate thousands of fully-human antibodies produced by the company’s VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies isolated from humans who have recovered from COVID-19. Importantly, the Regeneron team then selected the two most potent, non-competing and virus-neutralizing antibodies to create REGN-COV2 and then scaled up this dual-antibody cocktail for the company’s in-house platform VelociMab® and its manufacturing capabilities.
This helps them prepare for submitting the appropriate applications to then commence testing in humans (clinical trials).
As TrialSite has described, these two superior antibodies bind non-competitively to the critical receptor binding domain of COVID-19’s spike protein, which diminishes its ability to replicate and purportedly can attack spike variants that have spread throughout the world in human populations.
In a standard convalescent scenario, the supply of drug is completely limited by the number of donors. With REGN-COV2, this is not the case. UW’s Dr. Hartman commented, “That seems to be a big advantage over something that is donor dependent.”
UW-Madison Research on the Rise
TrialSite reported in August 2019 that the University of Wisconsin-Madison named Elizabeth “Betsy” Nugent as Chief Clinical Research Officer. UW had completed a self-evaluation, led by a well-known, highly respected clinical trials expert named Mary Westrick. They found its bureaucracy was getting in the way of excellence; change, focus and realignment were relevant discussion.
That UW leadership would take a hard look in the mirror exhibits a true foundation for the pursuit of excellence. In fact, all major academic medical centers should go through a similar journey as the one UW-Madison opted for in the pursuit of research excellence, safety and productivity. Ms. Nugent, who presented on the TrialSite Podcast, is on board and backed by committed leadership and dedicated and talented staff. UW is on the rise and is expected to become a favorite research site for drug sponsors.
Call to Action: TrialSite will be monitoring all three REGN-COV2 clinical trials. Interested in updates? Sign up for the daily newsletter.