Uncategorized

COVID-19: Drug Treatments and Vaccines

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:

  • AbCellera (Canada) used AI to identify more than 500 SARS-CoV-2 fighting antibodies in the blood sample of a patient who recovered from the disease. Eli Lilly (LLY) announced a partnership with AbCellera to develop COVID-19 drugs using these antibodies.
  • Abbott Laboratories (ABT) released a 5-13 minute COVID-19 test.  Abbott can now deliver 50,000 of these tests every day using over 18,000 existing diagnostic lab machines across the country.
  • Adaptive Biotechnologies (NASDAQ:ADPT)
  • AJ Vaccines
  • Aldeyra Therapeutics on a drug treatment for respiratory distress.
  • Alexion Ultomiris drug treatment to lower cytokine and chemokine levels, thereby reducing lung inflammation.
  • Alnylam Pharmaceuticals (NASDAQ:ALNY) and Vir Biotechnology (NASDAQ:VIR) have expanded their infectious disease collaboration to include three additional targets focused on host factors for SARS-CoV-2, including ACE2 and TMPRSS2 (both essential for the virus to enter and infect cells). GSK invested $250MM in Vir to fund Phase II studies for 2 preclinical antibody candidates — VIR-7831 and VIR-7832 — that have been engineered to target the SARS-CoV-2 spike protein.
  • Altimmune (ALT)
  • Amgen & Adaptive (NASDAQ:AMGN) — working on antibody treatment. Adaptive says it will use its platform to identify naturally occurring antibodies in the immune systems of COVID-19 survivors to find those that neutralize the SARS-CoV-2 virus that causes the disease. Amgen will then use those findings to develop therapies to treat COVID-19, and potentially prevent the disease among those with a greater risk of exposure, including health care workers.
  • Applied DNA Sciences
  • Applied Therapeutics’ (NASDAQ:APLT) AT-001 underway to treat acute lung inflammation and cardiomyopathy in critically ill COVID-19 patients.
  • Arcturus Therapeutics (NASDAQ:ARCT) & Duke U on a vaccine.
  • Berkeley Lights on a vaccine.
  • Biogen and WuXi Biologics have licensed technology from VIR for an antibody vaccine.
  • BioHaven on drug treatment.
  • BioNTech (BNTX) — plans to begin a human study of its Covid-19 vaccine in mid-late April or early May. Working with Pfizer.
  • CalciMedica on drug treatment candidates.
  • CanSino Biologics Inc.
  • Celularity
  • China CDC & Tongji University & Stermina
  • Clover Biopharmaceuticals (private) working with GSK
  • The Coalition for Epidemic Preparedness Innovations
  • Codagenix
  • CSL Behring on a vaccine.
  • CureVac (private) & Imperial College of London is working on an antibody vaccine.
  • CytoDyn (OTCQB:CYDY)
  • Dynavax Technologies (NASDAQ:DVAX) on a vaccine.
  • Eli Lilly (NYSE:LLY) on drug treatment candidates.
  • Enanta on vaccine candidates
  • EpiVax is working on a vaccine.
  • Evvivax
  • ExpresS2ion
  • Fudan University & Shanghai JiaoTong University & RNACure Bio
  • Genrex & EpiVax working with University of Georgia
  • GeoVax & BravoVax
  • Gilead Sciences (GILD) initiated two phase 3 trials for its drug remdesivir which was active against the SARS and MERS viruses in preclinical tests. COVID-19 is genetically similar.
  • GlaxoSmithKline (NYSE:GSK)  working with Clover
  • Greffex
  • Heat Biologics (NASDAQ:HTBX) with the University of Miami on a vaccine.
  • Humanigen’s (OTCQB:HGEN) lenzilumab for compassionate use for preventing and treating cytokine storm in severely ill COVID-19 patients. Received EUA from FDA.
  • ImmunoPrecise
  • InflaRx (IFRX) — InflaRx dosed the first patient in a European study of its coronavirus treatment, known as IFX-1.
  • Innovation Pharma on a vaccine.
  • Inovio Pharmaceuticals (INO) — Cleared to begin DNA vaccine human trials as of April 6th, 2020. Funding from the Coalition for Epidemic Preparedness Innovations (CEPI) and the Bill and Melinda Gates Foundation.
  • Institut Pasteur & Themis
  • Janssen
  • Johnson & Johnson (JNJ) on a vaccine to be manufactured by Emergent Biosolutions (EBS).
  • Karyopharm on treatment using its cancer drug.
  • Medicago (Canada) — leading vaccine platform
  • MilliporeSigma — Working with Edward Jenner Institute of Vaccine Research on vaccine and reducing vaccine manufacturing time down to two months.
  • Moderna (MRNA) — In mid-April, received $483MM from BARDA for clinical trials and expedited high-scale manufacturing. Experimental vaccine, mRNA-1273, is currently being tested in early-stage trial by the U.S. National Institutes of Health, with mid-stage trials set for Q2. Their 10-year collaboration agreement with Lonza U.S. (OTCPK:LZAGY) will see the companies produce up to a billion vaccine doses per year , and would cover additional products in the future.
  • Novartis (NASDAQ: NVS) — Running Hydroxychoroquine clinical trial. Also working with Incyte to study Jakafi as a treatment against respiratory distress triggered by the infection.
  • Novavax (NASDAQ:NVAX) on a COVID-19 vaccine. Novavax recently received approval for a flu vaccine.
  • Nuritas on peptide drug treatment.
  • Pfizer (NYSE:PFE) working with BioNTech on a vaccine.
  • Regeneron Pharmaceuticals (REGN) is working with the National Institute of Allergy and Infectious Diseases (NIAID) on IL-6 inhibition. Early results are not promising.
  • Roche Holdings (OTCQX:RHHBY) on drug treatment candidates including Actemra to block the immune signal IL-6 reducing cytokine storms. It is too expensive for global roll out and also has risks by weakening the immune system.
  • Sanofi Pasteur (NASDAQ:SNY) on drug treatment candidates.
  • Sequens and ViralClear are working on a broad-spectrum anti-viral treatment.
  • Serum Institute of India
  • Sinovac
  • Takeda Pharmaceutical (NYSE:TAK) on using antibodies from recovered patients.
  • Takis
  • TScan Therapeutics working on a vaccine.
  • Tiziana Life Sciences (NASDAQ:TLSA) on drug treatment candidates.
  • Tonix Pharma and Southern Research
  • Translate Bio (NASDAQ:TBIO) on a messenger RNA vaccine to create antibodies.
  • University of Pittsburgh
  • University of Oxford Jenner Institute on vaccine. Excellent progress in monkeys with adenovirus vaccine. Phase 2/3 study of 5000 people to start in May.
  • University of Queensland with Baylor, GSK and others
  • Vaxart (NASDAQ:VXRT) on a vaccine.
  • Vaxess on a vaccine delivery patch.
  • Vaxil Bio
  • VBI Vaccines on a vaccine for multiple types of coronaviruses.
  • Versatope Therapeutics on a vaccine.
  • Walter Reid Army Institute of Medical Research
  • Zhejiang Hisun Pharmaceuticals (China) is testing COVID-19 patients with favilavir, a drug approved for influenza.
  • Zydus Cadila

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:

  • mRNA
  • VLPs (Virus-like particles)
  • DNA Vaccines

Drug treatment types include:

mRNA Candidates

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.

Moderna’s mRNA 1273

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.

VLP Candidates

Medicago (Canada) — leading vaccine platform   

Potential use: inhibition of viral replication

Action: Not disclosed

Status: Medicago expects to initiate human trials by this summer (July/August 2020) with the objective of completing the development program and submitting a dossier to authorities by the end of next year (November 2021). The vaccine should be available after approval from respective regulatory authorities. Use plant-based production for manufacturing.

DNA Vaccines

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

Other Vaccines (Category TBD)

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.

Clover S-Trimer

Potential use: inhibition of viral replication

Action: Protein-based

Status:

Lopinavir + Ritonavir

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.

Monoclonal Antibodies

Remdesivir from Gilead (GILD)

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.

Fujifilm Toyama’s Avigan (Favipiravir)

Potential use: inhibition of viral replication in severe infections

Action: RNA polymerase inhibitor. Antiviral used in China and Japan for influenza.

Status: in clinical trials. Initial tests with 340 patients has led to viral clearance in a median of 4 days compared to 11 days for an alternative therapy.

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

Immunotherapy

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.

Adjuvants

Glaxo-Smith-Kline Pandemic Adjuvant Platform

Potential use: Enhances vaccines ability to stimulate the immune system

Action:

Status: Leverage existing Pandemic Adjuvant Platform

How useful was this post?

Click on a star to rate it!

Average rating / 5. Vote count:

Leave a Reply

Your email address will not be published. Required fields are marked *