Nirmatrelvir, the novel portion of the co-packaged medication, was first developed in the United States and was initially manufactured in small amounts in Groton, Connecticut, to support clinical trials, but the Freiburg facility in Germany was responsible for figuring out how to mass-produce the co-packaged medication on an industrial scale. Pfizer selected another factory in Ascoli Piceno, Italy, to assist the Freiburg factory with packaging tablets into blister packs. History
The primary data supporting the US Food and Drug Administration (FDA) emergency use authorization for nirmatrelvir/ritonavir are from EPIC-HR, a randomized, double-blind, placebo-controlled clinical trial studying nirmatrelvir/ritonavir for the treatment of non-hospitalized symptomatic adults with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Participants were adults 18 years of age and older with a prespecified risk factor for progression to severe disease or were 60 years and older regardless of prespecified chronic medical conditions. All participants had not received a COVID-19 vaccine and had not been previously infected with COVID-19. The main outcome measured in the trial was the proportion of people who were hospitalized due to COVID-19 or died due to any cause during 28 days of follow-up. Nirmatrelvir/ritonavir significantly reduced the proportion of people with COVID-19 related hospitalization or death from any cause by 88% compared to placebo among participants treated within five days of symptom onset and who did not receive COVID-19 therapeutic monoclonal antibody treatment.
Based on published reports and analyses of participant-level data, the expected survival rates 100 days after HSCT would be 21 to 31 percent for participants with severe hepatic VOD who received only supportive care or interventions other than defibrotide. Society and culture
Legal status
Defibrotide was approved in the European Union for use in treating veno-occlusive disease of the liver of people having had a bone marrow transplant in 2013; Gentium had developed it. At the end of that year, Jazz Pharmaceuticals acquired Gentium.In March 2016, the U.S. Food and Drug Administration (FDA) approved it for a similar use. Defibrotide is the first FDA-approved therapy for treatment of severe hepatic VOD, a rare and life-threatening liver condition. The FDA granted the application for defibrotide priority review status and orphan drug designation. The FDA granted approval of  Defitelio to Jazz Pharmaceuticals.Defibrotide was approved for medical use in Japan in June 2019.Defibrotide was approved for medical use in Australia in July 2020. References
Further reading
Richardson P, Aggarwal S, Topaloglu O, Villa KF, Corbacioglu S (December 2019). "Systematic review of defibrotide studies in the treatment of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS)". Bone Marrow Transplant. 54 (12): 1951–1962. doi:10.1038/s41409-019-0474-8. PMC 6957462. PMID 30804485. Richardson PG, Carreras E, Iacobelli M, Nejadnik B (June 2018). "The use of defibrotide in blood and marrow transplantation". Blood Adv. 2 (12): 1495–1509. doi:10.1182/bloodadvances.2017008375. PMC 6020812. PMID 29945939. External links
"Defibrotide". Drug Information Portal. U.S. National Library of Medicine.