COVID-19 Drug Research Roundup

COVID-19 Therapies:

A double-blind, randomized controlled trial has found that a self-administered nasal spray from SaNOtize Research & Development reduced viral load of the novel coronavirus by more than 95 percent within 24 hours in 79 people with confirmed COVID-19. SaNOtize’s Nitric Oxide Nasal Spray (NONS) also reduced viral load by more than 99 percent within 72 hours. In addition, the investigators found that NONS cleared SARS-CoV-2 by a 16-fold factor compared with placebo. There were no adverse events associated with NONS. Many of the participants in this trial were infected with the UK SARS-CoV-2 variant, suggesting the spray could be effective against more easily transmissible strains of the virus. Based on these results, SaNOtize says it plans to submit its product for emergency use in the UK and Canada.

An antiviral drug significantly reduced viral concentrations across several COVID-19 variants, according to preclinical in vitro data released by Bold Therapeutics last week. The treatment candidate, BOLD-100, demonstrated it is capable of selectively inhibiting stress-induced upregulation of master chaperone protein GRP78, an important component in a viral replication. The recent preclinical data from Bold suggest that BOLD-100 is effective against B.1.1.7, the UK SARS-CoV-2 variant. Bold says it has produced sufficient safety and efficacy data on the treatment and is in the completion phase of in vivo studies for the drug in COVID-19.

Eli Lilly’s recent request to revoke an Emergency Use Authorization (EUA) of its COVID-19 antibody monotherapy bamlanivimab has been granted by the FDA. Bamlanivimab was given an EUA in November for mild-to-moderate COVID-19. An “evolving variant landscape” was cited as the basis for the request. Eli Lilly says it plans to start supplying bamlanivimab in an antibody cocktail with etesevimab, rather than supplying it alone. The company says the antibody cocktail is capable of neutralizing a greater number of emerging COVID-19 variants in the states. The new request was granted after Lilly revised contracts with the U.S. that terminated purchase agreements for bamlanivimab monotherapy, effectively canceling up to 351,000 doses that were scheduled to be delivered by the end of last month.

The National Institutes of Health (NIH) has agreed to provide an initial investment of $155 million for the phase 3 ACTIV-6 trial, which will evaluate prescription and over-the-counter therapies as treatments for COVID-19 symptoms. The study will include adult patients with mild-to-moderate COVID-19 symptoms who do not require hospitalization. Up to 13,500 patients aged 30 years and older will be enrolled. Participants will be randomly assigned to either placebo or one of the prescription or over-the-counter treatments. These treatments will be sent through the mail and will be self-administered at home. Researchers will evaluate changes in symptoms over 14 days and will also examine the rates of hospitalizations and deaths within 28 days. Additionally, the investigators will evaluate long-term COVID-19-related symptoms at a 90-day follow-up period.

A phase 2 trial, launched by Todos Medical, is evaluating the antiviral agent NLC-V-01 (Tollovir) as a potential treatment for hospitalized patients with COVID-19. The study is being conducted at a single center in Jerusalem, and is enrolling 77 patients. Data from a previous randomized, open-label phase 1b trial featuring 27 hospitalized patients provided the chosen dose of NLC-V-01 for this new study. The primary endpoint includes time to discharge and time to clinical improvement. The researchers will also evaluate the rate of change in vital signs, such as heart rate, body temperature, respiratory rate and blood pressure. Other endpoints include the time it takes for a patient to receive treatment and achieve a negative COVID-19 test, deaths related to COVID-19, deterioration and need for mechanical ventilation or supplemental oxygen.

Roche has nixed two phase 2 studies, including one focused on astegolimab, a monoclonal antibody licensed from Amgen, as well as IL-22 inhibitor RG7880 (efmarodocokin alfa). The studies were examining these candidates as treatments for COVID-19-related pneumonia. The company did not offer details as to why the programs were pulled, instead pivoting to highlighting its partnership with Regeneron, specifically in regard to positive phase 3 trial results showing its casirivimab/imdevimab cocktail reduced COVID-19 symptomatic infections by up to 81 percent in clinical studies. The cocktail therapy also reduced hospitalization and death by 70 percent in the phase 3 trials.

A newly launched phase 3 clinical trial from Fujifilm Toyama Chemical is evaluating anti-influenza therapy Avigan (favipiravir) as a treatment option for COVID-19. While the drug selectively hinders RNA polymerase associated with influenza viral replication, Fujifilm believes this mechanism of action could be applied to COVID-19. The placebo-controlled clinical trial will be conducted in Japan and will look at the efficacy and safety of Avigan in patients with early COVID-19 who are at risk for severe symptoms. Participants will be aged 50 years and older and will have underlying comorbidities that make them particularly susceptible to the novel coronavirus. The new study is based on findings from a phase 3 study last year that showed treatment with Avigan led to accelerated symptom improvement in patients with early onset COVID-19.

The University of Oxford has launched a human challenge trial to see what happens to the immune system of people who are re-infected with COVID-19 a second time. Specifically, researchers will look to determine the types of immune responses needed to halt reinfection in people who have already been infected and recovered from COVID-19. The first phase of the study will seek to determine the lowest viral dose needed to initiate viral replication in the body without producing symptoms. A total of 64 healthy participants between 18 and 30 years of age who have previously recovered from COVID-19 will be enrolled in the study. Investigators will then re-expose patients to the original SARS-CoV-2 strain. Those who do experience symptoms will receive Regeneron’s monoclonal antibody therapy. In a second phase, participants will be infected by a standardized dose of the virus that was established in the first study phase.

COVID-19 Vaccines:

Data from a phase 1 study show Inovio’s DNA vaccine candidate INO-4800 generated robust T-cell responses against multiple SARS-CoV-2 variants. The vaccine also produced neutralizing antibodies against each tested spike protein variant, including variants from the UK, Brazil and South Africa. In the new phase 1 study, the vaccine candidate produced neutralizing antibodies against the Brazilian variant to the same degree as those produced against the original coronavirus strain. Positive interim data late last year showed the two-dose vaccine generated an overall immune response in 94 percent of patients by week six. The vaccine appeared to be safe, well-tolerated and associated with no serious adverse events by week eight. Inovio says it plans to report results from the phase 2 portion of a Phase 2/3 study in the second quarter of this year.

Aegis Life has launched a phase 1/2 trial examining its novel DNA COVID-19 vaccine candidate Covigenix VAX-001. The first participants have been dosed in the trial, which is being conducted by the Canadian Center for Vaccinology and IWK Health Center in Nova Scotia. Researchers will examine the safety and immunogenicity of the vaccine. Preclinical studies have shown the VAX-001 vaccine, when delivered as a single dose, induces potent humoral immunity as well as a promising response against SARS-CoV-2. Aegis, in conjunction with parent company Entos Pharmaceuticals, has also developed Covigenix VAX-002, a second DNA vaccine currently undergoing preclinical investigation. This second vaccine was designed to target emerging COVID-19 variants.

CanSino Biologics is launching clinical trials to study the efficacy of an inhaled COVID-19 vaccine capable of activating antibodies and T-cells in the airways of healthy recipients. Scientists from Hong Kong University, Xiamen University and Beijing Wantai Biological Pharmacy Enterprise developed the vaccine last September. The technology used to develop the company’s injectable COVID-19 vaccine, Adenovirus Type 5 Vector vaccine (Ad5-nCoV), was used to develop the new inhaled candidate. Researchers will be interested to see if the inhaled version of a COVID-19 vaccine is more effective than the injectable vaccines developed in China, as many of the COVID-19 vaccines from this region have demonstrated lower efficacy compared with candidates from Moderna and Pfizer-BioNTech.

Results of the second interim analysis of the phase 3 COVAXIN study show Bharat Biotech’s whole virion inactivated COVID-19 vaccine is 78 percent effective at preventing mild and moderate COVID-19 disease and 100 percent effective against severe COVID-19 disease. Bharat’s COVID-19 vaccine was developed in partnership with biopharmaceutical company Ocugen. The COVAXIN clinical trial included 25,800 participants between 18 and 91 years of age from India. There was a total of 2,433 people in the study who were over the age of 60, and 4,500 participants had comorbidities that made them more vulnerable to the effects of COVID-19. The second interim analysis was based on more than 87 symptomatic COVID-19 cases. In a subgroup of 8,000 participants, the efficacy of the vaccine against asymptomatic infection was 70 percent.

Valneva is comparing the immunogenicity of its adjuvanted, inactivated COVID-19 vaccine VLA2001 with AstraZeneca’s Vaxzevria. The pivotal phase 3 study will randomly assign 3,000 participants from the UK aged 30 years and older to either vaccine. The vaccines will be administered in two doses at four weeks apart. Another 1,000 participants under the age of 30 will receive two doses of VLA2001 given 28 days apart. The immunogenicity tests will be conducted in samples from 1,200 participants who test negative for SARS-CoV-2 at the screening phase. Valneva notes that if the data from this study are positive, it will seek to file regulatory submission to get approve for its vaccine.