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Draft / Research-in-Progress; Last updated on May 1, 2020.
The British Medical Journal maintains the latest guidelines for COVID-19 Medical Treatment Best Practices for Physicians. There is also an ongoing series of Scientific Collaboration on COVID-19 Treatment and Vaccines with hundreds of scientists. There are hundreds of companies pursuing solutions. Billions of vaccines will be needed. Here’s a timeline estimate on How Long a Vaccine Will Take. Expert estimates range from 9 months to 2 years.
BioWorld has a list of 254 therapeutics and 95 vaccines in development. Here is Keep Health’s list of ~80 companies working on drug treatments and vaccines:
Here’s the status of current drug treatments and vaccines against COVID-19 / SARS-CoV-2
From multiple sources, mostly medical journals.
Vaccines types include:
Drug treatment types include:
Limitations: Require cold storage. mRNA immune potency across the population may not be consistent. It may be weaker in older adults because their bodies cannot generate sufficient immune response. Existing adjuvant solutions don’t work for mRNA.
Potential use: inhibition of viral replication
Action: This experimental vaccine targets proteins on the outer structure of coronavirus. The vaccine works by introducing synthetic mRNA sequences into patients. These molecules allow for the host system to translate them into proteins that mimic those found on COVID-19. These proteins then circulate within patients and elicit an immune response that researchers hope will induce immunity to COVID-19.
Status: In Phase 1 clinical trial in Washington State with 45 people. Also running a trial in Atlanta. If successful, available for emergency use in Fall, 2020.
BioNTech and Pfizer
Two of their four vaccine candidates include a nucleoside modified mRNA (modRNA), one includes a uridine containing mRNA (uRNA), and the fourth vaccine candidate utilizes self-amplifying mRNA (saRNA). Each mRNA format is combined with a lipid nanoparticle (LNP) formulation. The larger spike sequence is included in two of the vaccine candidates, and the smaller optimized receptor binding domain (RBD) from the spike protein is included in the other two candidates. The RBD-based candidates contain the piece of the spike that is thought to be most important for eliciting antibodies that can inactivate the virus.
Have received approval to start trials in Germany. Seeking approval for trials in the US and China as well.
Inovio partnered with CDMO Ology Bioservices
Potential use: inhibition of viral replication
Action: Not disclosed
Status: Received $12MM in Department of Defense funding.
Applied DNA Sciences
Evvivax
Takis
Zydus Cadila
J&J COVID Vaccine & Two Backup Candidates
Potential use: inhibition of viral replication
Action: Not disclosed
Status: Human testing in September. Available for emergency use authorization in early 2021.
Potential use: inhibition of viral replication
Action: Protein-based
Status:
Potential use: inhibition of viral replication in severe infections used in combination to interferon beta.
Action: antivirals.
Status: in use and in trials.
Effect: Modest effect. Open label trial in 99 humans with severe COVID infection and on respirator showed non-statistically significant reduction in mortality. Unfavorable pharmacodynamics and negative clinical trial data so far.
Immunotech’s Ampligen ( Rintatolimod)
Potential use: inhibition of viral replication in severe infections
Action: Toll-like receptor 3 agonist antiviral agent.
Status: in clinical trials in Japan. Not promising despite success against SARS-COV-1.
Plitidepsin from PharmaMar (Spain)
Potential use: inhibition of viral replication in severe infections
Action: Antineoplastic agent that targets the elongation factor EF1A for halting replication of the virus.
Status: In vitro study results of plitidepsin on the human coronavirus HCoV-229E, which has a multiplication and propagation mechanism very similar to COVID19, have been positive with a potency of the nanomolar order. Awaiting government permission to start clinical trials in Spain.
Potential use: inhibition of viral replication
Action: antiviral nucleotide analog prodrug used in other human coronaviruses in tissue culture
Status: In clinical trials run by Gilead on both mild/moderate and severe patients in China. Initial data expected in mid-April. The NIH’s National Institute of Allergy and Infectious Diseases is recruiting patients for a phase 3 at multiple sites in the U.S., Japan, South Korea and Singapore. On April 10, the New England Journal of Medicine published early observational data showing clinical improvement in 36 out of 53 (68%) of patients treated with Remdesivir under compassionate use. Initial clinical results expected at end of April.
Hydroxychloroquine and chloroquine
Potential use: immunomodulation for controlling cytokine release syndrome in critically ill patients with COVID pneumonia. The original paper from China reported that 100 patients greatly improved. The Chinese government spokesperson indicated that the chloroquine has a certain effect in the treatment of COVID pneumonia. No specific numbers were provided. Donald Trump declared the drug a game changer. Dr. Anthony Fauci said that the drug’s promise is anecdotal.
Action: modulation of cytokine release. Moderate inhibition of viral replication suggested in in-vitro experiments published in Nature.
Status: in use and in trials. Has received emergency use authorization (EUA) from US Government. Some success in dialing back over-reaction from immune system in early results. On April 24th, the FDA cited hydroxychloroquine and chloroquine for “serious and potentially life-threatening heart rhythm problems, that have been reported with their use for the treatment or prevention of COVID-19.”
VA study shows higher death rate with hydroxychloroquine, more than double the control group rate.
Results from a study in China did not show improvement over placebo.
The University of Minnesota is conducting a trial with up to 3,000 patients. Columbia University in New York, and the University of Washington are each recruiting for 1,000-plus patient studies to test hydroxychloroquine as a preventive and treatment option for COVID-19. There are large international trials ongoing as well.
Novartis has donated 130 million doses. Novartis’ trial will randomize patients into three groups: hydroxychloroquine alone, hydroxychloroquine plus the antibiotic azithromycin, and placebo. All patients will receive standard of care on top of the experimental treatments.
TJM2
Potential use: treatment of lung injury by inhibiting inflammation
Action: monoclonal antibody against human granulocyte-macrophage colony stimulating factor
Status: under development
Gimsilumab
Potential use: treatment of lung injury by inhibiting inflammation
Action: monoclonal antibody against human granulocyte-macrophage colony stimulating factor, a proinflammatory cytokine
Status: under development
Anti-SARS-CoV-2 polyclonal hyperimmune globulin and monoclonal antibodies
Potential use: post-exposure prophylaxis and early intervention in high risk patients
Action: mix of antibodies against COVID obtained from patients who had the infection
Status: under development
Sarilumab and Tocilizumab
Potential use: damage control by cytokine release in severe infections that lead to intubation.
Action: Interleukin 6 inhibitor
Status: to start trials in April.
Methylprednisolone
Potential use: treatment of inflammation associated lung damage in severe infection and prevention of acute respiratory distress syndrome.
Action: immunosuppression
Status: in use and in trials.
Nitric oxide
Potential use: supportive measure for treating pulmonary complications, reversing pulmonary hypertension, improving severe hypoxia, and shortening the length of ventilatory support.
Action: direct smooth muscle relaxant.
Status: in use.
Fenprodil
Potential use: treatment of lung injury by inhibiting inflammation
Action: N-methyl-d-aspartate NDMA receptor antagonist for inhibiting inflammation
Status: under development
Remestemcel-L
Potential use: treatment of lung injury by regeneration
Action: Allogeneic mesenchymal stem cell for regenerating lung and inhibiting inflammation
Status: under development
Celularity CYNK-001
Potential use: eliminate replication and disease progression by killing infected cells
Action: “Studies have established that there is robust activation of NK cells during viral infection regardless of the virus class,” added Celularity’s chief scientific officer, Xiaokui Zhang, Ph.D. “CYNK-001 demonstrates a range of biological activities expected of NK cells, including expression of activating receptors such as NKG2D, DNAM-1 and the natural cytotoxicity receptors NKp30, NKp44 and NKp46, which bind to stress ligands and viral antigens on infected cells. “They also show the expression of cytolytic molecules perforin and granzyme B, which kill recognized infected cells.
Status: Received approval for 86 person trial with help of Rudy Giuliani.
Regeneron’s Kezvara, a rheumatoid arthritis drug
Potential Use: Prevent cytokine storms by inhibiting IL-6.
Status: Less-than-promising results from a mid-stage trial testing their rheumatoid arthritis drug Kevzara in COVID-19 patients. An ensuing Phase 3 trial will continue, redesigned to only include patients defined as critical, including those requiring mechanical ventilation, high-flow oxygenation, or to be cared for in an intensive care unit, given that sicker patients seemed to show some improvement while taking the drug. The late-stage trial will also now only include a higher dose of the drug (400 milligrams) and the placebo.
Glaxo-Smith-Kline Pandemic Adjuvant Platform
Potential use: Enhances vaccines ability to stimulate the immune system
Action:
Status: Leverage existing Pandemic Adjuvant Platform
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