COVID-19 Drug Research Roundup

COVID-19 Vaccines:

AstraZeneca’s trial of its COVID-19 vaccine candidate AZD1222 is expected to restart this week following a lengthy FDA review of a serious adverse event that occurred during the trial. The study had been paused since Sept. 6 after a trial participant in the UK fell ill with what might have been a rare spinal inflammatory disorder. While it’s unclear how the FDA will characterize the illness, some believe the agency will require trial investigators to add information about the adverse event to consent forms.

A patient also died in a late-stage AstraZeneca vaccine trial being run in Brazil, according to the country’s regulator. The drugmaker declined to provide details about the event but said that the investigation into the death did not warrant stopping the study.

Additionally, a UK study found that AZ’s vaccine candidate delivered a strong immune response and worked as intended. Researchers at the University of Bristol confirmed through genetic sequencing and protein analysis that the vaccine performed as it is programmed to do and successfully produced a hefty immune response.

Moderna announced that it has finished enrolling 30,000 participants in its phase 3 vaccine trial. The large-scale trial is being run with support from NIH’s National Institute of Allergy and Infectious Diseases and HHS’ Biomedical Advanced Research and Development Authority.

ImmunityBio and NantKwest have dosed their first patient in a phase 1 trial of COVID-19 vaccine candidate hAd5-COVID-19. The vaccine was designed to target both the inner nucleocapsid and the outer-spike protein on SARS-CoV-2 while activating T-cells and antibodies against the virus. The trial is being conducted at the Hoag Hospital in Newport Beach, Calif. Investigators are in the process of recruiting healthy adults up to 55 years of age. The primary goal of the study will be to test the safety and reactogenicity of two doses of hAd5-COVID-19.

Another vaccine candidate from Sanofi and Translate Bio has demonstrated positive immune responses against SARS-CoV-2 in preclinical research. The preclinical study examined three doses of their candidate, MRT5500, using a two-dose administration schedule spaced three weeks apart. The two companies announced they will initiate a phase 1/2 study of their COVID-19 vaccine in the fourth quarter of 2020.

Preliminary data show that BBIBP-CorV, an investigational COVID-19 vaccine out of China, appears safe and effective at generating antibody responses to SARS-CoV-2. The study included 600 healthy volunteers between the ages of 18 and 80. The antibody responses were produced by day 42 after vaccination. People older than 60 years of age showed a slower response than younger participants. The study did not look at whether the vaccine can protect people against COVID-19.

The Serum Institute of India along with Bharat Biotech will soon start phase 3 trials of intranasal COVID-19 vaccine candidates, pending regulatory approval in India.

A total of 400 patients will be recruited into Ose Immunotherapeutics’ first two stages of trials studying the company’s T-cell COVID-19 vaccine. According to Ose, these trials are set to start at the end of 2020 and will examine the vaccine’s safety and associated immune response. The company will then conduct phase 3 studies from September 2021 with a partner, but the name of the partner has not been disclosed. The company’s vaccine candidate is based on the rationale that a subgroup of killer T-cells can be trained to attack SARS-CoV-2-infected cells. Pending results of its research, Ose hopes to distribute its vaccine in Europe and the U.S. in 2022.

Open Orphan’s hVIVO has struck a deal with the UK government to develop a model that would manufacture a SARS-CoV-2 challenge virus to be used in human challenge studies of COVID-19 vaccines. Under terms of the agreement, hVIVO will receive $43.5 million to develop this model. The human challenge studies, if approved by regulators as well as an ethics committee, could start in January 2021, with results expected by May 2021. The studies would be conducted in line with a partnership with Imperial College London and the Royal Free London NHS Foundation Trust.

COVID-19 Therapies:

The FDA has approved Gilead Sciences’ remdesivir for treating hospitalized COVID-19 patients, marking the agency’s first full approval for a COVID-19 treatment. The agency based its decision on results from three clinical trials that included patients hospitalized with mild-to-severe COVID-19. The trial run by the NIH’s National Institute of Allergy and Infectious Diseases found that the median time to recovery from COVID-19 was 10 days for the remdesivir group as opposed to 15 days for the placebo group. The drug is now “widely available in hospitals across the country,” according to the company.

On the other side of the spectrum, findings from the World Health Organization’s (WHO) 11,266-patient Solidarity trial show that remdesivir, in addition to three other antivirals, had “little or no effect” on hospitalized patients with COVID-19. But Gilead Sciences, maker of remdesivir, is clapping back at the organization, saying the Solidarity trial’s design had concerning limitations. According to Gilead, the trial had significant heterogeneity in trial implementation and patient population, suggesting the study results may not be conclusive. Additionally, the Foster City, Calif.-based biopharmaceutical company criticized the early data from the Solidarity trial by stating it had not gone through rigorous peer review. Gilead added that the evidence generated in this trial do not agree with “more robust” data from other randomized trials that show remdesivir actually helped hospitalized patients with COVID-19.

The National Institutes of Health (NIH) is kicking off a phase 3 trial of two existing drugs and one investigational agent to evaluate their potential to control cytokine storm, an immune system overreaction in COVID-19 patients. The NIH is using three candidates, Johnson & Johnson’s Remicade (infliximab), Bristol Myers Squibb’s Orencia (abatacept) and AbbVie’s investigational agent cenicriviroc (CVC), after narrowing down a list of more than 130 immune-modulator drugs. The study plans to enroll more than 2,100 hospitalized adults with moderate-to-severe COVID-19 at medical facilities in the U.S. and Latin America, and the trial is expected to last approximately six months.

Treatment with immune modulator and rheumatoid arthritis drug tocilizumab was associated with a reduced risk of death in an observational study of critically ill patients with COVID-19. Slightly more than 27 percent of patients who received the Genentech-made drug within two days of ICU admission died within 30 days, compared with 37 percent of patients who did not receive the treatment. The study, conducted by researchers at the Brigham and Women’s Hospital in Boston contrasts with findings from a separate study that show tocilizumab did not reduce the risk of mortality in hospitalized patients with COVID-19 and pneumonia.

In a randomized controlled trial led by the Indian Council of Medical Research (ICMR), the use of convalescent plasma did not reduce the risk of mortality or prevent progression of COVID-19 in 464 patients across 39 hospitals in India. Convalescent plasma is currently allowed for the off-label treatment of patients with moderate COVID-19. But based on the findings from this study, the ICMR is considering removing this therapy from India’s clinical management protocol for the disease.

IncellDx has announced its involvement in a phase 2 clinical trial studying Pfizer’s FDA-approved CCR5 antagonist Maraviroc as a treatment for COVID-19. The oral medication will be administered for seven days during this study. IncellDx will perform a Maraviroc-specific CCR5 Receptor Occupancy assay in addition to its IncellKINE RUO Cytokine Storm quantification panel. Additionally, the company will conduct immune profiling with T-cell exhaustion, macrophage polarization and SARS-CoV-2 plasma viral load assessments.