I received a very interesting question the other day regarding the history of aviptadil and any regulatory milestones associated with it as a medicine.
Below, I outline a brief history of aviptadil and why we believe it may offer patients suffering respiratory distress the opportunity to regain health and get back home to their families.
Vasoactive intestinal peptide (VIP) has been studied for more than 50 years. In that time, the medical community has developed a keen understanding of what the peptide does and doesn’t do in the human body.
To our knowledge, aviptadil, which is a VIP, was never developed commercially beyond a phase 2 clinical trial for any indication other than erectile dysfunction before NeuroRx’s (NRx Pharmaceuticals, Inc.) involvement in March 2020.
VIP causes dilation of blood vessels by binding to the vasoactive intestinal peptide one receptor in the arteries. It has a very short-lived effect, which is suitable as an erectile dysfunction medicine but not as effective as a pulmonary hypertension medicine. The effect on the pulmonary arteries is shown in studies to be very short-lived. However, through research, we have discovered and disclosed our understanding that the peptide used in the pulmonary hypertension trial failed because the peptide was surrounded by a buffer. That’s why we made sure not to place ZYESAMI™ in a buffer.
In the lung, VIP binds to a different receptor, the vasoactive intestinal peptide two receptor, and has a very different effect because it binds to the alveolar type 2 cells. Aviptadil was studied in acute respiratory distress syndrome (ARDS) in 2004 by Drs. Sami Said and J. Georges Youssef. Only eight patients were treated because Dr. Said had access to very limited quantities of aviptadil. Dr. Said retired shortly thereafter, never publishing the results. Dr. Youssef was able to resurrect the data this year, showing that seven of eight patients in the ICU on a ventilator survived and left the ICU. The results were submitted posthumously in Dr. Said’s name https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3662952
After Dr. Said retired, the biotech company that continued the work on aviptadil, unfortunately, decided not to pursue the ARDS indication, preferring to focus on chronic lung disease. The intellectual property was owned by the Research Foundation for the State University of New York and licensed by NeuroRx (now a subsidiary of NRx Pharmaceuticals, Inc.) in August 2020.
It is inaccurate to say that VIP failed when studied to treat ARDS. For seven of eight patients to survive the ICU back in 2004 was unprecedented. It’s unfortunate but not unique in biotech that a highly promising investigational medicine got shelved and fell through the cracks.
Physicians and scientists have studied VIP for 50 years in the laboratory. Investigator-led phase 2 research of inhaled applications of aviptadil was conducted under US Food and Drug Administration (FDA) authorization. However, until NeuroRx formulated it under the FDA’s Current Good Manufacturing Practice and FDA granted NeuroRx a research investigational new drug application in March 2020, no commercial formulation or study of aviptadil was undertaken under any health authority. We hope that COVID-19 will be the first of many indications for which ZYESAMI™ helps people return home to their families, in better health.