Pharma, Pharmaceutics and Biotechnology Conference

Treatment landscape of COVID-19 has rapidly evolved over the last few months, driven by both the urgency of the pandemic and the unpredictable mutations of the virus. To this end, a multi-pronged approach will be presented during this session, ranging from antiviral agents to monoclonal antibodies and immunomodulatory drugs targeting different stages of infection by SARS-CoV-2 and pathological consequences. Early management strategies remain focused on antiviral agents. Of these, remdesivir remains a drug of choice for patients who require hospitalization and oxygenation but not ventilation.

Its ability to decrease the duration of hospitalization by only a few days may restrict its use mostly to intravenous formulations; hence, further research studies on oral and subcutaneous formulations of this drug to enable increased use are being done. Oral antivirals like Paxlovid (nirmatrelvir/ritonavir) are emerging leaders in the outpatient treatment of high-risk cases. Paxlovid has an advantage of having dual action: nirmatrelvir inhibits protease and ritonavir boosts the plasma levels. Thus, if started early, it reduces viral load; drug interactions with statins, among others commonly prescribed drugs, remain a significant limitation that the clinician needs to consider.

Another important oral antiviral is molnupiravir, an error-prone replication for inducing copying errors in viral replication. Having shown a potential reduction in hospitalization in the more vulnerable, its mutagenic concern has balanced extensive use. Ongoing clinical trials have focused on dosing regimens to try and further allay these concerns with continuing efficacy.

The additions of monoclonal antibodies added a new layer of defense, not only in their attenuation of more severe disease but also within high-risk populations. Early versions of sotrovimab and bebtelovimab seemed promising to target conserved epitopes on the spike protein, making them effective against many variants. Nevertheless, newer variants of SARS-CoV-2, including the Omicron sub variants, have led to a decline in the efficacy of many of the monoclonal antibodies, and utility is now largely dependent on regional distribution of variants. Recent work has targeted monoclonal therapies with increased neutralizing capacity. Immunomodulatory therapies have transformed the management of critically ill patients with COVID-19.

For patients requiring mechanical respiratory support, corticosteroids remain the standard of care and have decreased mortality from nearly 70% to less than 50% by dampening exaggerated inflammation. However, along with corticosteroids, tocilizumab, an IL-6 receptor antagonist, has proven helpful in addition to modulating cytokine storms of severe respiratory failure in patients with rapidly progressive respiratory failure.

Another repurposed drug is a JAK inhibitor, namely, Baricitinib which has another advantageous mechanism of direct antiviral activity by inhibiting the endocytosis of SARS-CoV-2.Even as SARS-CoV-2 continues to evolve, and treatment protocols must be equally dynamic. The landscape of therapeutics is highly dynamic due to emerging variants and changes in clinical evidence that influence the preferred pathways of treatment.

This session will cover the status of these drugs and the environment in which ongoing trials and research set the next generation of therapeutics for COVID-19. The participants also discussed the potential use of combination therapies, antiviral and immunomodulatory, to improve patient outcomes across the various stages of infection.