SARS-CoV-2 Treatment and Vaccines

The emergence and rapid spread of a novel severe acute respiratory syndrome (SARS)-like coronavirus SARS-CoV-2, since 2019, is destroying global health and economy. Compared to SARS-CoV, which contributed to the outbreak in 2003, many SARS-CoV-2 patients develop low levels of neutralizing antibodies and suffer prolonged illness. This is because SARS-CoV-2 evades the immune surveillance more effectively while maintaining high cell infectivity. Thus, to curb SARS-CoV-2 spread it's important to develop viable treatment options and preventive vaccination

In October 2020, the FDA approved the intravenously administered antiviral drug Veklury (remdesivir) for use in hospitalized adult and pediatric patients 12 years of age and older and weighing at least 40 kilograms. Remdesivir (GS-5734), developed by Gilead Sciences (NASDAQ: GILD), is an inhibitor of the viral RNA-dependent, RNA polymerase, and has been proven efficacious in three randomized, controlled clinical trials, including a randomized, double-blind, placebo-controlled clinical trial (ACTT-1) - the gold standard for evaluating the efficacy and safety of investigational drugs. The ACTT-1 trial showed that Remdesivir leads to a five-day faster recovery in hospitalized patients overall, and a seven-day faster recovery in people who required oxygen support at baseline, compared with placebo.

In November 2020, the FDA granted emergency use authorization (EUA) to a monoclonal antibody therapy called Bamlanivimab. It was approved for non-hospitalized adults and children over age 12 with mild to moderate COVID-19 symptoms who are at risk for developing severe COVID-19 or the need of hospitalization. Bamlanivimab, developed by Eli Lilly & Company (NASDAQ: LLY), is a neutralizing IgG1 monoclonal antibody that binds to the receptor binding domain of the spike protein of SARS-CoV-2, making it more difficult for the virus to infect human cells. The approval of this investigational drug was based on an ongoing randomized, double-blind, placebo controlled, Phase 2 dose finding trial. This is a single dose therapy that must be given intravenously within 10 days of developing symptoms. An interim report of the trial revealed that patients treated with the monoclonal antibody had a reduced risk (3% versus 10%) of being hospitalized or visiting the ER within 28 days after treatment, compared to patients given a placebo.

Recently (November 2020), Pfizer (NASDAQ: PFE) with BioNTech SE (NASDAQ: BNTX) and Moderna (NASDAQ: MRNA) revealed positive results regarding the efficacy of their respective Covid-19 vaccines. Both groups have developed mRNA vaccines that encode a stabilized perfusion SARS-CoV-2 spike protein, in contrast to conventional vaccinations that use weakened viruses or purified viral signature proteins. In a Phase 3 study that began in July and enrolled 43,538 participants from the US and abroad, BioNTech and Pfizer's mRNA-based Covid-19 vaccine candidate, BNT162b2, demonstrated an efficacy of above 90% at 7 days after the second dose. Pfizer and BioNTech expect to produce up to 50 million vaccine doses globally in 2020 and up to 1.3 billion doses by the end of 2021, and as of November 20th have filed for EUA with the FDA. The first interim analysis of the Phase 3 study of Moderna's mRNA-1273 vaccine was based on 95 cases of Covid-19 (out of 30,000 adult US participants), of which 90 cases of Covid-19 were observed in the placebo group versus 5 cases observed in the mRNA-1273 group, resulting in a vaccine efficacy of 94.5%. In addition, none of the infected patients who received the vaccine developed severe Covid-19, while 11 (12%) of those who received the placebo did. Moderna, too, intends to submit for EUA with the FDA in the coming weeks based on the final analysis of 151 cases and a median follow-up of more than 2 months.

An interesting question is which of the two vaccine candidates will gain more wide-spread use in the coming months? While the technologies and efficacies of both vaccines are comparable, one main difference is how they are stored. Pfizer's vaccine has to be stored at temperatures less than minus 30 degrees Celsius, which has raised practical concerns about how they could be shipped and disseminated. Moderna's vaccine, in contrast, can remain stable with regular refrigeration (2-8 degrees Celsius) for 30 days. Another point to consider is that while Moderna's venture into the vaccine space is relatively new, Pfizer has a rich history in vaccine R&D, with the prior development of 13 vaccines. Nevertheless, the therapeutic advancements outlined in this article offer some hope during this debilitating pandemic. It will be interesting to see the instrumental role of these interventions in managing and possibly eliminating Covid-19 spread.

References:

1. https://www.health.harvard.edu/diseases-and-conditions/treatments-for-covid-19

2. https://www.gilead.com/news-and-press/company-statements/gilead-sciences-statement-on-updated-veklury-covid19-treatment-guidelines

3. https://www.fda.gov/media/143602/download

4. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine

5. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against

6. https://www.nature.com/articles/d41586-020-03166-8

7. https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy

8. https://www.nature.com/articles/d41586-020-03248-7

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