On Wednesday, July 21, 2021, Prof Jonathan Javitt, MD, MPH, Chairman and CEO of NRx Pharmaceuticals, participated in a panel discussion hosted by the Disease Prevention & Control Summit. The specific panel discussion focused on small molecules and repurposed medicines for COVID-19 treatment. Jonathan received several questions from those watching the panel discussion. Below, are Jonathan’s answers to questions posed to him during the panel discussion.
Q: How happy is the NRx team with the results so far in bringing ZYESAMI™ to market? Is it time to relax when we get EUA, or will NRx be continuing its efforts to study ZYESAMI™ in the inhaled form?
A: While the NRx team believes the clinical trial has demonstrated that ZYESAMI™ “may be effective” in achieving improved survival and recovery in patients suffering from COVID-19 respiratory failure, and hopes that the FDA will agree, it’s not possible to be “happy” about the results of a clinical trial in which patients died, even if they were more likely to die on placebo. Conducting research in the midst of a public health emergency is beyond the imagination, as has been the process of trying to rush compassionate care medicine to the bedside of patients in need.
Regarding the inhaled study, NRx is not taking its foot off the gas. We are eager to work with the I-SPY platform and continue our inhaled ZYESAMI™ study, and we very much look forward to the data readouts from that study. It is also important to note that we will be preparing studies in Acute Respiratory Disease Syndrome and other conditions where ZYESAMI™ may offer patients a new therapeutic value.
Q: Is aviptadil THE SOLUTION for covid?
A: Unfortunately, the Sars-Cov-2 virus is an incredibly complicated virus causing multiple problems for people infected with it. From a patient’s kidneys and lungs to their brains and immune responses, the COVID-19 virus has shown its impact on many organs in the body and shown its lethality in millions around the world. There will likely never be one solution for those critically ill with COVID-19. We certainly believe, however, that ZYESAMI™ (aviptadil) can be part of the treatment paradigm, and provide those most ill with the Coronavirus a better chance at recovery.
Q: When will NRx get approval from the US Food and Drug Administration (FDA)?
A: Naturally, we cannot speak for the FDA. We agreed with the FDA in 2020 regarding the endpoints that needed to be demonstrated in order to gain Emergency Use Authorization (EUA), and we continue to respond to questions from the FDA regarding the data underlying those endpoints.
Q: Why is the FDA taking so long to approve ZYESAMI™?
A: Although rumors of a delayed review have been circulated in various forums, the reality is that the EUA file was submitted on May 31, 2021, and has been at the FDA for less than two months. Clinical research and review take time to perform properly, and we believe that NRx has acted with unprecedented speed to develop a potentially life-saving drug.
We began this project in March 2020 with electronic files from Relief Therapeutics and with the majority of the old data on aviptadil trapped in a bankruptcy liquidator’s warehouse in Essen, Germany. Based on the strength of Stonybrook University’s archived IND from 2004, FDA gave us permission to proceed with a clinical study in 48 hours. Ten weeks later, we had developed a never-before formulated intravenous solution of aviptadil, received FDA’s approval of our formulation records, and treated the first patient. During the next seven months, in the midst of a public health crisis, we enrolled 196 patients. On February 22, 2021, the last patient completed the clinical trial. We announced top-line results about 30 days later, and during the subsequent 60 days, completed thousands of pages of statistical analysis in order to submit a clinical study report to FDA.
We are the first to wish that we could have done more in less time. However, we are confident that our team of fewer than 30 people has beaten any standard pharmaceutical timeline, giving patients the best possible chance to survive this lethal disease. Now, we are doing all we can to ensure the FDA has all information needed to make an informed decision as soon as possible.
Q: What is involved in receiving approval for ZYESAMI™ in Israel? Is that effort underway?
A: The Israeli Ministry of Health has already granted approval for the compassionate use of ZYESAMI™ and is monitoring the US FDA process. Israel does not have its own Emergency Use Authorization review process.
Q: How is the study going in the Nation of Georgia? Are there any findings so far?
A: As we said in our press release, investigational drug is on its way to Georgia, and we are training ICU physicians.
Q: Will ZYESAMI™ be available in poorer countries?
A: NRx is committed to providing ZYESAMI™ where patients are in need throughout the world. NRx leaders are engaged with health departments and ministries all over the globe, educating them about ZYESAMI™ and the potential it may offer to patients in those countries suffering from the most severe forms of COVID-19.
Q: Is NRx filing for biomarker regulatory approval from the FDA?
A: NRx is submitting a biomarker letter of intent to the FDA as part of the regulatory agency’s biomarker program, authorized under the 21st Century Cures Act. The linkage between the clinical effect of aviptadil on survival and recovery and a measurable biologic change in cytokine levels provides a basis for seeking a biomarker-based regulatory path as envisioned by the 21st Century Cures Act. The lethal impact of “cytokine storm” is associated with mortality in a variety of lethal conditions, including Acute Respiratory Distress Syndrome, a common cause of death in sepsis, and amniotic fluid embolus, a primary cause of maternal death during pregnancy.
Q: Is there any data available regarding the impact ZYESAMI™ has on any of the growing numbers of COVID-19 variants?
A: As we continue to treat patients with COVID-19, an increased number of those patients have Delta and subsequent variants. We are actively monitoring their clinical course to attempt to identify specific activity against those variants.
Q: Does ZYESAMI help with myocarditis?
A: Vaso intestinal peptide (VIP) is known to have a general anti-inflammatory effect on cells that line blood vessels as well as cells that line the lungs. Therefore, it’s reasonable to anticipate there might be an effect on myocarditis, but we have not yet studied COVID-related myocarditis as an entity.
Q: Is there a study of ZYESAMI™ in Brazil planned, or are there hospitals in Brazil planning to join NRx’s Expanded Access or Right to Try programs?
A: We anticipate that patients in Brazil will be exposed to ZYESAMI™ as the National Institutes of Health ACTIV3b/TESICO trial extends to Brazil.
Q: When can we expect interim data from the ongoing trials for both intravenous and inhaled ZYESAMI™?
A: The FDA discourages the release of interim data from clinical intervention trials, and releasing interim data involves a substantial statistical “penalty” that forces significant increases in patient enrollment. Thus, we do not anticipate interim results will be released.
Q: What has been the most rewarding aspect throughout the process? What drives you?
A: I entered the drug development world as a physician and public health researcher. I will never forget the conversation I had with my son Matthew in 1998 when he learned that I had left my full-time faculty role to lead my first company. He came to me with great concern (at the age of 6) and asked, “Daddy, aren’t you a doctor anymore?” I answered that I had been given a chance to work on a product that had the potential to save more lives in a day than I could likely save in a career of patient care. I promised him that if I no longer had that opportunity, I would return to caring for patients one at a time. Today, he is starting his own career as a physician and healer.
We at NRx are driven by the extraordinary opportunity we have been given to help patients and families at a time when the world is challenged by a once-in-a-century public health crisis. The calls and letters we get from patients and families, including from those who have not had a successful outcome, keep us going around the clock on a mission that is nearing the 18-month mark.
We at NRx know that our work can produce better outcomes for patients and get them back home to their families and normal, daily lives sooner. That patient-centric dedication to excellence and science applies equally to our psychiatry program and to everything we do.
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