Silver Bullet April 30 - COVID cures in development, Novavax prepares to file
A weekly update on all things COVID-19. News, public health guidance, trends, breakthroughs, and thousands of scientific papers distilled down to what you need to know right now.
Enough about vaccines. What about a cure?
As vaccines have rolled out in the US and around the world, the focus on fighting COVID-19 has centered almost exclusively on vaccine effectiveness, mass vaccination goals, and herd immunity. Epidemiologists have emphasized that continued use of non-pharmaceutical interventions (NPIs) like masking and limiting indoor gatherings will be necessary to slow or stop the virus. Although vaccines and NPIs have already proven they can turn the tide of the pandemic, there are many reasons why mass vaccination may not be enough to fully stop it. Among those are vaccine hesitancy and new variants such as the South African variant B.1.135 that shows signs of vaccine resistance. Successful therapeutics and antivirals could be the missing bridge between a constantly receding and resurging worldwide endemic virus, and true eradication of the virus globally.
Some of therapies have already been identified and approved for emergency use including dexamethasone, monoclonal antibodies, and the antiviral drug remdesivir. These treatments have blunted the fatality rate of COVID-19, but they are just a small fraction of the arsenal or new and repurposed therapeutics that the biotech industry is currently advancing through clinical trials. That pipeline, includes novel drug compounds, repurposed old drugs, high tech biologics like antibodies, and completely new technology like CRISPR and mRNA. At least 70 COVID-19 candidates are in human clinical trials, according to Regulatory Focus. Here are a few examples:
Eli Lilly’s rheumatoid arthritis drug, Olumiant, received emergency use authorization in the US for COVID-19 in November 2020, and the company recently reported Phase 3 results showing a significant decrease in death in hospitalized patients with COVID-19. The European Medicines Agency has promised to quickly review the drug for approval.
Pfizer just kicked off a Phase 1 study of its oral antiviral candidate PF-07321332, which it says has shown potent activity against the virus in vitro. The drug is a protease inhibitor that prevents the virus from entering the cell. The study in healthy adults will assess safety and tolerability of the drug. It is also testing another protease inhibitor, PF07304814, in people hospitalized with COVID-19.
The NIH is carrying out three late-stage clinical trials of the blood thinners apixaban and heparin for treatment of COVID-19.
A little way behind these later stage therapies, the preclinical pipeline of therapeutics features groundbreaking new technology comparable to the mRNA platform used for the Pfizer-BioNTech and Moderna COVID-19 vaccines. In May 2020, Alnylam Pharmaceuticals partnered with Vir Biotechnology to develop a COVID-19 antiviral based on RNA interference (RNAi), in which short RNAs silence gene expression by attacking messenger RNA. Basically it’s a custom off switch for any gene you could think of. And Alnylam is thinking of a few. For example, they have RNAi drugs that switch off expression of problematic genes in TTR-mediated amyloidosis and hepatic porphyria. Read more…
Novavax prepares FDA vaccine filing
Politico reports that Novavax is preparing to file for FDA authorization for its COVID-19 vaccine, potentially beating the AstraZeneca vaccine to the US market. If approved, it would be the most traditional vaccine design available for SARS-CoV-2, being comprised of a nanoparticle containing a full-length spike protein. The Moderna, Pfizer-BioNTech, Johnson and Johnson, and AstraZeneca vaccines all contain instructions for making the spike protein in the form of mRNA or DNA.
Novavax reported in January that its vaccine was 89.3% effective in its Phase 3 trial in the UK against symptomatic illness at a time when the B1.117 variant was prevalent. In a separate Phase 2b study in South Africa where the B1.135 “escape” variant was prevalent, the vaccine was 60% effective. Novavax has promised 100 million doses to the US after receiving $1.6 billion in funding from Operation Warp Speed. However, it has also pledged 1.1 billion doses for low- and middle-income countries like India. India’s Serum Institute will produce over a billion doses of the vaccine, and most of those will go to COVAX, a global vaccine equity initiative. However, the Serum Institute has suffered a shortage of raw materials for vaccine manufacture due to a temporary US restriction on exporting those materials resulting from invocation of the Defense Production Act. The Biden administration recently agreed to lift those restrictions in order to supply India with raw materials for manufacturing, as well as test kits, ventilators, and PPE.
Vaccines reduce risk of transmissible infection
A new report from the CDC based on real world data finds that the mRNA based vaccines from Moderna and Pfizer-BioNTech are 90% effective at preventing laboratory-confirmed COVID-19, regardless of whether symptoms are present. This means that vaccinated individuals are unlikely to be asymptomatic carriers. The study also found that the vaccines were 80% effective starting 14 days after the first dose.
Risk of death elevated for six months after COVID-19, even mild cases
COVID-19 survivors can experience an array of symptoms for months after infection, even those with initially mild cases. A new study in Nature finds that survivors also have an almost 60% greater risk of death in the six months following their illness. These deaths may be caused by long term complications of COVID-19, but are often not recorded as COVID-19 deaths. The lingering health conditions resulting from COVID-19 can affect nearly every organ and system of the body. The severity of symptoms and long term risk of death correlated with the severity of the initial illness.
In depth
What’s in a name? COVID vaccine ‘passports’ vs ‘verification’ by Serena Marshall and Lara Salahi, Medpage Today
SARS-CoV-2 elimination, not mitigation, creates best outcomes for health, the economy, and civil liberties, by Miguel Oliu-Barton, et a., The Lancet