The FDA announced their commitment to not only conducting clinical trials of convalescent plasma, but also facilitating access to the treatment for use in patients with severe or immediately life-threatening infections.1
Convalescent plasma is one of the many treatment pathways being relentlessly pursued by the FDA and researchers in the United States and around the globe. Convalescent plasma involves antibody-rich blood products that are taken from blood donated by individuals who have recovered from COVID-19 virus.
Single patient emergency Investigational New Drug Applications (eINDs) will be used to facilitate access to convalescent plasma for use in patients with life-threatening COVID-19 infection, according to the agency. FDA Commissioner Steven Hahn, MD, in Thursday’s presidential coronavirus briefing also mentioned compassionate use conditions, in which a physician can request the application of an experimental drug on a patient. 1, 2
Beyond these limited stipulations is the rapid development and commitment to clinical trials evaluating the efficacy and safety of drugs with the potential to treat the novel coronavirus. Chloroquine and its less toxic derivative hydroxychloroquine, a drug that President Trump has mentioned as having potential to treat mild-to-moderate COVID-19, has already experienced early shortages. ASHP has listed hydroxychloroquine sulfate tablets on its current drug shortages list. Hydroxychloroquine is currently approved to treat malaria, lupus, and rheumatoid arthritis. 2, 3
The president also mentioned the experimental drug remdesivir (Gilead), which is being evaluated for use to treat COVID-19 in clinical trials. The 2 Phase 3, randomized, open-label, multicenter trials began in March 2020 and intend to enroll around 1000 participants in total. The first study aims to analyze the results from both a 5-day and 10-day dosing duration of the drug, with standard of care for patients who are severely ill, whereas the second study uses the same method to analyze patients with moderate COVID-19, compared with standard of care only. 4
Some early clinical trials have had disappointing results. Johnson & Johnson found no evidence that their HIV drug darunavir (Prezista), alone or in combination with other HIV drugs, has any effect against the novel coronavirus, despite hopes that HIV medicines could speed COVID-19 patient recovery. Similar results for lopinavir-ritonavir (Kaletra), another HIV drug, were also reported by AbbVie. 5
Expanding to a global scope, China’s National Health Commission approved tocilizumab (Actemra, Roche) for patients with severe complications from SARS-CoV-2, the virus that causes coronavirus. Tocilizumab is approved for the treatment of rheumatoid arthritis (RA) in the United States; the drug’s ability to inhibit high Interleukin 6 (IL-6) protein levels, which propel many inflammatory diseases, has led to China’s approval for the treatment of serious lung damage and high IL-6 levels caused by COVID-19. 6
Greg Frank, PhD, director of Working to Fight AMR and director of infectious disease policy at the Biotechnology Innovation Organization, sees the COVID-19 outbreak as potentially an issue related to antimicrobial resistance. 7
“Much of our modern medical care is reliant on antibiotics,” Dr Frank said in an interview with Drug Topics®.
“Everyday these products keep patients safe and enable those medicines and interventions to work. What they do is prompt an evolutionary response from our adversaries, where these bugs can develop mechanisms to resist these drugs, and render them ineffective. In practice, when you have a resistant infection, some portion of our arsenal of microbials will be ineffective to that patient. What we’re seeing now is increasingly, there are now patients infected with bugs that are resistant to everything we have. The danger we have is that as resistance rates continue to go up, and they are only going up, we’ll reach a point where many modern medical procedures will be too risky to perform, and anyone can have an infection that can end their life.”
Concerning the current pandemic, Dr Frank said that data is limited when considering the antimicrobial relevance. He cited other viral respiratory diseases – the flu in particular – that have very high rates of patients contracting a secondary bacterial infection.
“The majority of influenza deaths here in the US are due to those secondary bacterial infections, not necessarily the flu by itself,” Frank said.
Studies from China show a portion of the patients–especially those who have to be put on ventilators– are at risk for secondary infections. 8
The FDA aims to keep the public’s safety a priority through the urgency of finding an effective coronavirus treatment. In last Thursday’s presidential press briefing, Hahn said, “Let me make one thing clear: The FDA’s responsibility to the American people is to ensure that products are safe and effective.”
1. Coronavirus (COVID-19) Update: Daily Roundup, March 24, 2020 [news release]. FDA website. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19.... Published March 24, 2020. Accessed March 24, 2020.
2. The White House. 3/24/20: Members of the Coronavirus Task Force Hold a Press Briefing. YouTube website. https://www.youtube.com/watch?v=4R75JwHCA1U. Published March 24, 2020.
3. Hydroxychloroquine Sulfate Tablets. ASHP website. https://www.ashp.org/Drug-Shortages/Current-Shortages/Drug-Shortage-Deta.... Published March 24, 2020. Accessed March 24, 2020.
4. Remdesivir Clinical Trials. Gilead website. https://www.gilead.com/purpose/advancing-global-health/covid-19/remdesiv.... Accessed March 24, 2020.
5. Orelli B. Abbvie’s HIV Drug Kaletra Fails to Help COVID-19 Patients. The Motley Fool website. https://www.fool.com/investing/2020/03/19/abbvies-hiv-drug-kaletra-fails.... Published March 19, 2020. Accessed March 24, 2020.
6. Liu R, Miller J. China approves use of Roche drug in battle against coronavirus complications. Reuters website. https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg/c.... Published March 4, 2020. Accessed March 24, 2020.
7. AMR Industry Alliance. AMR Industry Alliance website. https://www.amrindustryalliance.org. Accessed March 25, 2020.
8. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020; doi: https://doi.org/10.1016/S0140-6736(20)30566-3.