COVID-19 Drug Research Roundup

COVID-19 Vaccines:

Results from two phase 1/2 trials out of Russia have shown that the country’s controversial two-shot COVID-19 vaccine from the Gamaleya Research Institute was safe and led to antibody generation in all 76 adult volunteers. These findings follow the abrupt August approval of the vaccine by the Russian government, which was criticized as the approval preceded phase 3 trials of the candidate. The researchers of this trial, who recently published their findings in The Lancet, said the study is limited by its small sample size and lack of a placebo or control group. A 40,000-volunteer phase 3 trial of the vaccine is in the works, according to Russia’s state news agency. This larger trial will be conducted in Russia, Saudi Arabia, the Philippines and the United Arab Emirates. Brazil and India are also on the potential list of countries where the vaccine will undergo phase 3 testing.

AstraZeneca (AZ) has had to halt its phase 3 COVID-19 vaccine trial after a single UK patient experienced a serious adverse event, but its CEO believes that the trial will stay on track as long as the safety review goes well. AZ chief Pascal Soriot offered assurances that the company’s timeline of filing for vaccine approval by the end of the year should not be impacted as long as the safety review determines the trial may start up again. It has not been determined that the vaccine had anything to do with the serious adverse event and no conclusions have yet been made.

A phase 1/2 trial of AstraZeneca’s COVID-19 vaccine candidate AZD1222 has begun in Japan. The trial will be conducted across multiple sites in the country and will test the efficacy and safety of the vaccine in up to 250 people aged 18 years and over. The pharma company has signed an agreement with the Japanese government to supply up to 120 million doses of AZD1222 starting in 2021, pending approval. A phase 3 trial of the vaccine has already started in the U.S. This trial will enroll more than 30,000 participants. Additionally, late-stage trials of the candidate are underway in the UK, Brazil and South Africa.

Preclinical studies of Janssen’s lead SARS-CoV-2 investigational vaccine candidate, Ad26.COV2.S, showed that the vaccine prevented severe clinical disease in animal models. The recently published results of these studies also showed that the vaccine candidate produced an immune response and reduced the risk of adverse events associated with severe COVID-19, including pneumonia, weight loss and death.

Mexico has announced it is participating in phase 3 trials investigating Russia’s Sputnik V COVID-19 vaccine. Once permission is granted by Mexican regulators, the vaccine will be transported to Mexico and will bested in several thousand volunteers in October.

International researchers, led by the Washington University School of Medicine in St. Louis, are initiating a global trial to determine whether the measles, mumps and rubella (MMR) vaccine offers protection against SARS-CoV-2 infection in frontline healthcare workers. The trial, which aims to enroll up to 30,000 healthcare workers across the globe, is being co-led by University College London and the University of the Witwatersrand in Johannesburg, both via the CROWN (COVID-19 Research Outcomes Worldwide Network) Collaborative, an initiative funded by a $9 million grant from the COVID-19 Therapeutics Accelerator. Researchers from centers in African, European and North American countries will participate.

Brazil’s technology institute Tecpar, which previously agreed to produce Russia’s Sputnik V COVID-19 vaccine, has announced that it plans to conduct a 10,000-volunteer phase 3 study on the vaccine at the beginning of next year. The study will be conducted in Brazil following approval from the country’s ANVISA health regulator. According to Tecpar, the institute plans to produce the vaccine for Brazil in the second half of 2021 and will also seek to export the vaccine to other Latin American countries.

Thermo Fisher has agreed to produce Inovio’s COVID-19 vaccine, INO-4800, in 2021. While Inovio expects to produce and distribute up to 100 million doses, the biotech company is in ongoing litigation with another manufacturer that controls much of the intellectual property (IP) used to produce their vaccine products. According to Inovio, this manufacturer appears to be unable to make commercial quantities of their vaccine but is refusing transfer of the IP to another manufacturer.

SpyBiotech, partnered with the Serum Institute of India, has initiated a phase 1/2 trial of a virus-like, particle-based COVID-19 vaccine based on the hepatitis B vaccine. A few hundred volunteers have already been recruited, and the first dosing of patients have been reported. The trial is investigating the safety and efficacy of the vaccine at different doses, which will be controlled against an adjuvant. Data from the trial are expected to be available in October or November. The company hopes to begin a phase 3 trial of the vaccine before the end of 2020.

Preclinical data from a phase 2/3 trial of BioNTech’s and Pfizer’s COVID-19 mRNA vaccine candidate BNT162b2 show the vaccine produces strong anti-viral effects against an infectious SARS-CoV-2 challenge in mice and nonhuman primates. Treatment with the vaccine also protected against lung infection in all of the SARS-CoV-2 challenged rhesus monkeys and cleared the nose of detectable viral RNA within three days following infection. Findings from this trial, according to BioNTech, support the move toward phase 3 testing of the vaccine.

Sinovac Biotech has announced that its inactivated COVID-19 vaccine candidate is safe and is associated with immunogenicity, according to results of phase 1/2 clinical studies of healthy adults aged 60 years and above. The trials, conducted in China, included 421 healthy elderly volunteers who were randomized to receive either the vaccine candidate or a placebo. No vaccine-related serious adverse events were reported, and the seroconversion rate for elderly patients was similar to that observed in an adult group aged 18 to 59 years.

CanSino Biologics is expecting to begin a late-stage clinical trial this month in Pakistan for potential COVID-19 vaccine Ad5-nCoV. The trial will enroll approximately 8,000 volunteers, including healthcare workers. Participants will be enrolled over four months and will be followed for up to one year after receiving the vaccine candidate or placebo.

COVID-19 Therapies:

The University of Chicago Medicine is launching the BLAZE-1 trial, a phase 2 trial testing the LY-CoV555 antibody against the SARS-CoV-2 spike protein. The antibody, developed by Eli Lilly and AbCellera, was also tested in a phase 1 trial that began in June. In this phase 2 portion, a total of 22 participants with mild-to-moderate COVID-19 will be treated with LY-CoV555 to test the antibody’s effects on reducing viral load, symptoms and signs of infection. All patients in this study will be followed for up to 90 days. Three different doses of the therapy will be tested. UChicago Medicine will ultimately seek to enroll 400 patients across several centers.

FSD Pharma has submitted an investigational new drug application to the FDA for FSD201, a potential therapy for severe COVID-19. The company plans to launch a randomized, double-blind and multicenter study of the therapy. The trial will be conducted at 25 to 30 sites in North America and will examine the efficacy and safety of FSD201 at twice-daily doses of 600 mg or 1200 mg in conjunction with standard of care compared with standard of care alone in hospitalized patients with COVID-19.

Therapeutic biotech company Cynata Therapeutics has begun enrolling patients in its COVID-19 trial, which is investigating the use of the company’s proprietary Cymerus mesenchymal stem cells (MSC) product for the treatment of severe COVID-19. The open-label trial will start by enrolling 24 adult patients receiving intensive care for COVID-19 and respiratory distress. A total of 12 patients will be randomly assigned MSC infusions plus standard of care, while the other 12 patients with be randomized to standard of care alone.

The National Institutes of Health has launched two phase 3 trials studying different types of blood thinners as COVID-19 treatments. The trials look to determine at what disease stage the blood thinners might be effective for COVID-19 patients. One study will test a low and high dose of heparin for preventing clotting and improving outcomes, with the potential for testing additional anti-thrombotic agents depending on trial progress. The other will assess whether blood thinners can reduce cardiovascular or pulmonary complications in newly diagnosed patients that have not been put in the hospital. A third trial that has not yet started will evaluate blood thinners in patients that have been discharged after being hospitalized for moderate to severe COVID-19.

Corvus Pharmaceuticals’ investigational monoclonal antibody CPI-006 has shown promise for treating COVID-19, according to early results from a small phase 1 trial. All 10 participants that received either a 0.3-mg or 1-mg dose of the drug generated high levels of antibodies to the SARS-CoV-2 virus within a week of a single infusion. Patients saw clinical improvement and no drug-related safety issues were reported.

Diffusion Pharmaceuticals has dosed the first two patients in its phase 1b trial of a synthetic carotenoid, trans sodium crocetinate (TSC), for hospitalized COVID-19 patients with low blood oxygen levels. The 24-patient trial, which is being conducted at the Romanian National Institute of Infectious Diseases, is measuring the drug’s safety and tolerability and its effects on arterial blood oxygenation. The data will be used to guide a follow-on efficacy study that will be conducted in the U.S. and Europe. Preclinical models have shown that the drug increased oxygen availability and provided functional benefit for acute lung injury and hemorrhagic shock.