The Food and Drug Administration (FDA) has authorized initiation of a phase 2 trial of vazegepant (Biohaven, New Haven, CT) for potential treatment of COVID-19 pulmonary complications. Vazegepant is an intranasally delivered calcitonin gene-related peptide (CGRP) inhibitor antagonist in phase 3 trials for the treatment of migraine.
Vlad Coric, M.D., Chief Executive Officer of Biohaven commented, "Given the unprecedented global threat to life that COVID-19 infection represents, there is an urgent need to test novel approaches to mitigating the consequences of the infection, including reducing the hyper-immune reaction that drives much of the morbidity and mortality in the pulmonary effects of this viral disease." Dr. Coric added, "This pandemic is a call to action for our entire industry. I am grateful to our collaborators at the pulmonary institute at Thomas Jefferson and the team at Biohaven that moved so quickly to develop a clinical protocol and submit this IND to the FDA in the weeks after the pandemic first developed. We owe a debt of gratitude to the scientists at the NIH, FDA, academic centers and pharmaceutical companies who are working hard to study therapies that might battle this terrible disease—the innovative efforts of the true unsung scientific heroes of this crisis will only be fully recognized once better treatments are developed to treat COVID-19."
Jesse Roman, MD, Professor, Jane & Leonard Korman Respiratory Institute—Jefferson Health and National Jewish Health, Thomas Jefferson University, and co-Principal Investigator in the proposed COVID-19 study commented, "Hospitals and our health care system are being overwhelmed by those patients who are progressing to serious COVID-19 infection. There is an urgent need to identify treatments that can mitigate the inflammatory process in these patients and help stabilize our response to the pandemic. It's critical that we move quickly to test immune-modulating drugs like vazegepant and other agents as to assess if they can provide some benefit."
The phase 2 double-blind randomized placebo-controlled safety and efficacy trial will enroll participants hospitalized for COVID-19 who require supplemental oxygen. The effect of vazegepant vs placebo on pulmonary symptoms, progression to respiratory support, and survival will be measured. The study will be overseen at Biohaven by Steven Schnittman, MD, a seasoned infectious disease clinical researcher and pharmaceutical drug developer. Michael Baram, MD, of the Thomas Jefferson University, Pulmonary Critical Care and Emergency Medicine, will be the principal investigator for the study.
Acute lung injury upregulates TRP channels to activate CGRP release, which contributes to acute and chronic lung injury that activates acute respiratory distress syndrome (ARDS). The CGRP release also influences release of cytokines and interleukins, affecting the immune response. Because COVID-19 leads to an acute insult of pulmonary epithelia, it is hypothesized that a CGRP receptor antagonist may potentially blunt the severe inflammatory response to delay or reverse the path towards oxygen desaturation, ARDS, requirement for supplemental oxygenation, artificial ventilation, or death.
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