COVID-19 Drug Research Roundup
Pfizer and BioNTech reported last week that the trial of their codeveloped vaccine BNT162b2 has generated safety data on 44,000 trial participants, 12,000 of whom were followed for at least six months after administration of the second dose, giving U.S.-based Pfizer sufficient safety data to submit a biologics license application to the FDA, according to CEO Albert Bourla. The vaccine currently is being distributed in the U.S. under FDA Emergency Use Authorization (EUA) only. The companies also reported that the vaccine is 91.3 percent effective against COVID-19 and 95 percent to 100 percent effective against severe COVID-19 in patients age 16 and older. The companies added that the vaccine was 100 percent effective in preventing COVID-19 cases in South Africa.
Meanwhile, a 2,260-person phase 3 study shows Pfizer/BioNTech’s COVID-19 vaccine is well-tolerated and 100 percent effective at preventing symptomatic disease among adolescents age 12 to 15 years. In total, the researchers observed 18 cases of COVID-19 in patients randomized to placebo vs. zero cases in adolescents who received the two-dose vaccine. Side effects observed in study participants were reportedly similar to those seen in patients age 16 to 25 years. The data from this trial, while not yet peer-reviewed, will be submitted to the FDA and serve as an amendment to the current vaccine’s EUA for patients age 16 years and older.
A real-world study led by the Centers for Disease Control and Prevention shows Pfizer/BioNTech’s and Moderna’s COVID-19 vaccines are effective at preventing SAR-CoV-2 infections in healthcare and essential workers. The study, which included 3,950 people from six states, tested the efficacy of the two messenger-RNA vaccines between December 2020 and March of this year. The risk of infection among participants at two weeks after a single vaccine dose was reduced by approximately 80 percent. Additionally, the risk of SARS-CoV-2 infection was reduced by 90 percent at two or more weeks following the second dose. These findings validate previously reported phase 3 data but also show how the vaccines work outside a clinical trial setting.
New results from a phase 3 clinical trial show Humanigen’s monoclonal antibody lenzilumab significantly reduces the risk of death among hospitalized patients with COVID-19. The study enrolled 520 adult patients with COVID-19 across 29 clinics in Brazil and the U.S. Patients in this trial represented a real-world, high-risk population as they often presented with various comorbidities, including an elevated body mass index. The patients in this study who were treated with lenzilumab plus other therapies, including steroids and/or Gilead Sciences’ remdesivir, experienced a 54 percent increased likelihood of survival after 28 days of treatment compared with patients who received only placebo and other therapies. The company says it plans to seek an EUA from the FDA for lenzilumab based on the positive study findings.
In a phase 2 study, treatment with a COVID-19 antibody combination consisting of Eli Lilly’s bamlanivimab plus Vir Biotechnology’s and GlaxoSmithKline’s VIR-7831 was associated with a 70 percent reduction in high viral load after only one week. There were no serious adverse events associated with treatment in this study. The companies involved in the trial suggest the combination regimen could offer increased protections against SARS-CoV-2 variants that have developed resistance to bamlanivimab, according to preclinical data. GSK and Vir recently filed for an EUA with the FDA for VIR-7831 after another trial found the monoclonal antibody candidate led to an 85 percent reduction in the risk of hospitalization and death compared with placebo. Previously, the FDA authorized Lilly’s bamlanivimab for COVID-19 and also subsequently authorized bamlanivimab with the company’s other COVID-19 antibody drug etesevimab.
South Korea’s Aptabio has announced plans to launch a phase 2 trial of the company’s oral drug candidate APX-115 for the treatment of COVID-19. The candidate is a transmembrane enzyme NADPH oxidase inhibitor that has undergone investigation in Europe for diabetes-related complications. Data from a European phase 1 trial showed the drug did not lead to any observable safety signals. COVANCE will conduct the study, which plans to enroll 80 patients with COVID-19 from 12 U.S. medical centers. Pending positive results from the phase 2 trial, Aptabio intends to submit an EUA application for APX-115 following a confirmatory trial.
The recently launched 12-month PROTECT-V trial from the University of Cambridge is investigating the effectiveness of different therapies to help prevent vulnerable people, including kidney patients and immunocompromised individuals, from developing COVID-19. Up to 2,250 people across the UK are expected to be enrolled in the clinical trial. A similar trial conducted by the University of Nottingham will examine the effectiveness of different therapies for reducing SARS-CoV-2 transmission and serious illness among residents and staff of care homes. This two-year trial, termed PROTECT-CH, will be launched in May of this year and will recruit 12,000 elderly residents from more than 400 care homes.
Findings from an ongoing phase 1b study from Sorrento Therapeutics show the company’s human allogeneic adipose-derived mesenchymal stem cells, dubbed COVI-MSC, led to signs of clinical improvement when administered every other day among patients with COVID-19-induced acute respiratory distress or acute respiratory distress syndrome. The nine patients who were treated with COVI-MSC had a noticeable reduction in the need for high inspired oxygen concentration. Also, these patients were transferred out of the intensive care unit and discharged from the hospital within a few days of their third therapy infusion. The researchers observed no infusion-related safety events. Sorrento says it’s currently working with the FDA to develop a phase 2 trial, which will be placebo-controlled and conducted across several sites in the U.S., Brazil and Mexico. The company is also working to identify the appropriate sample size and data necessary to support an EUA.
Interim findings from a phase 2b/3 study conducted by NeuroRx and Relief Therapeutics show intravenous RLF-100 (aviptadil) improved survival and recovery in critically ill patients with COVID-19 at 60 days following treatment. The randomized trial included 196 patients, all of whom received standard-of-care in conjunction with either RLF-100 or placebo. Approximately 75 percent of patients who received RLF-100 recovered at two months, while 55 percent of patients who received placebo also recovered at this follow-up period. The survival rates were 84 percent in the RLF-100 arm vs. 60 percent in the placebo group. While the FDA did not approve an EUA for aviptadil last year based on data from an open-label study, the two sponsors of this phase 2b/3 trial hope the new data are strong enough to support an authorization.
The FDA has granted an EUA for Becton Dickinson’s (BD) antigen test that detects SARS-CoV-2, influenza A and influenza B in a single test. The 15-minute test is called BD Veritor System for Rapid Detection of SARS-CoV-2 & Flu A+B assay and is run on the company’s BD Veritor Plus System. Currently, more than 70,000 active BD Veritor Systems are being used at hospitals, doctors’ offices, urgent care clinics, retail pharmacies, nursing homes, schools and other locations in the U.S. According to BD, the new test is expected to launch this summer in time for the 2021 to 2022 flu season. Healthcare providers can order this test if patients are suspected to have COVID-19, influenza A or influenza B within a six-day period of symptom onset.
SaNOtize’s early nitric oxide nasal spray (NONS) significantly reduced SARS-CoV-2 levels among 79 confirmed COVID-19 cases in a randomized, double-blind phase 2 trial. In the first 24 hours, there was an average 95 percent viral load reduction among participants. The viral load declined by more than 99 percent within 72 hours of treatment with NONS. Overall, the researchers concluded that treatment with NONS was associated with an accelerated clearance of the novel coronavirus by a factor of 16-fold when compared with placebo. Given that this study was conducted in the UK, most patients in the trial had been infected with the UK variant of SARS-CoV-2. No adverse events were recorded in the trial. SaNOtize says it soon plans to apply for emergency authorization in the UK and Canada.