COVID-19 Drug Research Roundup

COVID-19 Therapies:

A combination of Eli Lilly’s bamlanivimab and etesevimab antibodies has gained Emergency Use Authorization from the FDA for treatment of mild-to-moderate COVID-19 in patients age 12 and older who are at high risk of progressing to severe COVID-19 and/or hospitalization. The European Medicines Agency currently is reviewing the cocktail, which the latest findings showed reduced the risk of hospitalization or death by 70 percent, for conditional marketing authorization. Lilly also is assessing a combination of bamlanivimab with a monoclonal antibody developed by Vir Biotechnology and GlaxoSmithKline.

Roche’s arthritis drug Actemra significantly reduced mortality among hospitalized patients, according to researchers in the University of Oxford RECOVERY trial. The drug, a monoclonal antibody, also shortened the time to recovery and reduced the need for ventilation.

Turn Therapeutics has enrolled the first participants in its randomized COVID-19 treatment and prevention trial of Hexagen, the company’s flagship antimicrobial product. The therapy will be administered intranasally three times per day for five days, and researchers will investigate its efficacy for reducing viral load and uptake of SARS-CoV-2 at certain infection points in the nose. The clinical trial expects to enroll 100 patients with mild-to-moderate COVID-19 and 50 healthcare providers. Turn says it expects an initial data readout in early March.

A common asthma medication from AstraZeneca, Pulmicort (budesonide), significantly reduced symptoms of COVID-19 when administered within seven days of symptom onset, according to a small phase 2 study in the UK. The study, conducted in collaboration with the University of Oxford, enrolled 146 people who were assigned to either budesonide or standard of care alone. Patients given inhaled budesonide experienced a 90 percent reduction in visits to urgent care or hospitalization after 28 days of treatment. Treatment with budesonide was also associated with a reduction in fever and persistent symptoms.

NeuroRx launched a phase 2/3 trial to investigate whether its inhaled therapy Zyesami (aviptadil) can reduce the chances of COVID-19 progression to respiratory failure when administered during early stages of the disease. The placebo-controlled U.S. trial, conducted in collaboration with UCI Health of the University of California, Irvine, expects to enroll 144 patients. If the therapy is effective in this population, NeuroRx will study the efficacy of aviptadil in a second cohort of outpatients with COVID-19.

Immuno-oncology company Agenus has released positive findings from a phase 1 trial of its iNKT cell therapy in patients with moderate-to-severe COVID-19 symptoms. The study was conducted through Agenus’s subsidiary, AgenTus Therapeutics. Preliminary findings show that 75 percent of the four patients were extubated and released after treatment with the company’s proprietary allogeneic iNKT cell therapy. Half of the patients were extubated within a 24-hour period following dosing. Currently, AgenTus is actively accruing and treating patients with severe COVID-19 symptoms with the study drug. Researchers expect to complete dose escalation in the first half of 2020, and the company says it hopes to launch a phase 2 trial with data readouts expected in this year’s fourth quarter.

A phase 2 study in the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program, spearheaded by the National Institute of Allergy and Infectious Diseases, will study a combination of Brii Biosciences’ BRII-196 and BRII-198 experimental monoclonal antibodies to see if this regimen is effective for treating COVID-19. The phase 2/3 ACTIV-2 study will enroll 220 patients with mild or moderate COVID-19, half of whom will receive intravenous infusions of BRII-196 and BRII-198. The remaining half of the study participants will receive a placebo infusion. Assessments will be conducted in the clinic or at home, and all patients will be followed for 72 weeks. A phase 3 study in the ACTIV program that’s part of the master protocol ACTIV-3 has also begun evaluating the efficacy and safety of AstraZeneca’s investigational long-acting antibody combination AZD7442 in hospitalized patients with COVID-19. Another sub-study in the ACTIV-3 master trial is investigating GlaxoSmithKline’s and Vir Biotechnology’s experimental monoclonal antibody VIR-7831 against COVID-19.

A small phase 2 study recently showed that treatment with Veru’s oncology candidate VERU-11 was associated with a significant and clinically meaningful reduction in the proportion of hospitalized patients with high-risk COVID-19 who experienced treatment failure compared with treatment with placebo. The study, which enrolled 40 hospitalized patients at high risk of acute respiratory distress syndrome, found that treatment with the candidate resulted in an 81 percent relative reduction in treatment failures compared with placebo. Also, a significantly lower proportion of patients aged 60 years and up had a significantly lower rate of treatment failures if they were treated with VERU-11. Veru says it plans to speak with the FDA on the possibility of launching a larger test in a 200-patient phase 3 study.

Northwell Health and Cold Spring Harbor Laboratory are now enrolling adult patients into a fully virtual randomized, double-blind, placebo-controlled trial to study the efficacy and safety of famotidine as an outpatient treatment for COVID-19. The trial is enrolling patients with mild-to-moderate COVID-19 symptoms across the greater New York area. Participants will be randomized to receive either placebo or famotidine 240 mg per day for up to 14 days. Patients in the study will use an Apple iPad from their home along with a scale, thermometer, fitness tracker, spirometer and pulse oximeter to record and track treatment outcomes.

ReCoVa-19, a Cambridge-based startup, is supporting a clinical trial in the UK to help identify early interventions for COVID-19. The trial, dubbed the Platform Randomized trial of Interventions against Covid-19 In older peoPLE (PRINCIPLE) trial, will look for potentially effective COVID-19 treatments that can be taken at home and will recruit people over 65 years and those 50 years and older with a comorbidity. The study is being run by Oxford University and is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research.

COVID-19 Vaccines:

Sinovac Biotech’s COVID-19 vaccine CoronaVac has been granted a conditional marketing authorization (CMA) from the China National Medical Products Administration (NMPA). Rolling submission for the vaccine began in September 2020. To date, Sinovac made more than 40 submissions to the NMPA. The CMA was based on two-month data from phase 3 clinical trials. The final results from these trials have not been made public, and Sinovac says efficacy and safety results need to be confirmed. Currently, ConronaVac is being used in Indonesia, Brazil, Turkey and Chile under emergency use approval.

The South African government has placed a temporary hold on trials studying the AstraZeneca and University of Oxford COVID-19 vaccine after results show the AZD1222 candidate features low efficacy against the South African SARS-CoV-2 variant. A 2,000-person South African study validated previous findings by showing the vaccine featured high efficacy against the original nonvariant COVID-19 strain, but the vaccine came up short against preventing mild-to-moderate cases of COVID-19 caused by the relatively new South African strain. In response, the University of Oxford and its partners are looking to develop a second generation of the vaccine to target the more infectious variant.

Iran has unveiled its newest COVID-19 vaccine project that sees the launch of a new phase 1 trial studying Razi Cov Pars, a COVID-19 vaccine developed at the
Razi Vaccine and Serum Research Institute. The phase 1 trial will enroll 13 volunteers age 18 to 55. One day after the announcement of the new project, Iran launched a campaign to vaccinate the country’s entire population of 80 million. The country plans to start off this campaign by using Russia’s Sputnik V vaccine.

Interim data from a phase 1 study in Taiwan show COVAXX’s two-dose COVID-19 vaccine candidate, UB-612, elicits robust antibody responses. These responses appear comparable to responses in human convalescent sera. All trial participants had neutralizing antibodies following the two-dose regimen, and the vaccine was generally well-tolerated. COVAXX is conducting phase 2 trials of its UB-612 vaccine in Taiwan and plans to initiate phase 2/3 trials of the candidate in India with Aurobindo.