COVID-19 Drug Research Roundup

COVID-19 Therapies:

Eli Lilly’s and Incyte’s Janus kinase (JAK) inhibitor Olumiant (baricitinib) proved unable to significantly reduce progression to noninvasive ventilation for COVID-19 patients in a phase 3 trial, though the drug still managed to significantly reduce the risk of death. The companies announced last week that the phase 3 study didn’t meet its primary endpoint, with only 2.7 percent of patients given the JAK inhibitor proving less likely than those who received standard of care to progress to ventilation or death, a finding that was not statistically significant, the companies said.

Grifols has announced that its investigational immunoglobulin therapy CoVIg-19 showed no benefit in 593 hospitalized adults with COVID-19 who participated in the phase 3 INSIGHT-013 trial. The therapy, which consists of antibodies from patients who have recovered from COVID-19, was developed in partnership with Takeda Pharmaceutical, CSL Behring, Emergent BioSolutions and other companies involved in the CoVIg-19 Plasma Alliance. The late-stage trial was conducted across 63 sites in the U.S. as well as 10 other countries. The investigators assessed whether the plasma treatment reduced the risk of COVID-19 progression when added to standard of care, including Gilead Sciences’ remdesivir. There was no difference between patients who received CoVIg-19 vs. standard of care only in regard to clinical status at day seven. Following the announcement of the study results, the CoVIg-19 Plasma Alliance announced it plans to disband.

Tiziana Life Sciences announced it will soon launch a phase 2 trial for Foralumab, the company’s nasal anti-CD3 human monoclonal antibody, in hospitalized patients with moderate-to-severe COVID-19. The randomized, placebo-controlled trial will be conducted in Brazil. Patients enrolled in the study will receive standard-of-care background therapy with or without Foralumab. A previous study in patients with mild-to-moderate COVID-19 found that the nasally administered anti-CD3 antibody treatment was well-tolerated and associated with reduced pulmonary and systemic inflammation. Treatment with Foralumab in this prior study reduced several markers of inflammation, including C-reactive protein and interleukin-6. Another recent study from Harvard Medical School and a Brazilian CRO also found that Foralumab reduced pulmonary and systemic inflammation.

Sound Pharmaceuticals is planning to launch two phase 2 trials to study SPI-1005, an oral capsule comprising small-molecule ebselen, in patients with moderate-to-severe COVID-19. While the therapy was developed for neurotologic, neuropsychiatric and respiratory indications, a Cooperative Grant award of $3.1 million from the National Institutes of Health’s National Center for Advancing Translational Sciences has provided an incentive for Sound to investigate SPI-1005 in treating the novel coronavirus. A total of 120 patients with moderate-to-severe COVID-19 will be enrolled in the two randomized, placebo-controlled trials. Patients will receive either SPI-1005 or placebo for up to seven or 14 days. The primary outcome is the number of participants with treatment-related adverse events. Additional secondary study outcomes include clinical improvement and degree of supplemental oxygen required during treatment.

Findings from a phase 1 study show that UNION therapeutics’ COVID-19 inhaled and intranasal niclosamide candidates are safe when administered to healthy people. The study included 44 healthy participants who were randomized to either one of the UNI911 candidates (UNI91103 or UNI91104) or placebo. The trial met its endpoints and demonstrated that the niclosamide solution was well-tolerated when administered both intranasally and through inhalation. There was no indication of systemic accumulation of the products in the blood. These findings pave the way for future studies that will examine the prophylactic and treatment efficacy of these drug candidates in patients with COVID-19.

COVID-19 Vaccines:

Johnson & Johnson (J&J) is now dosing adolescents with its COVID-19 vaccine candidate Ad26.COV2.S in an ongoing, placebo-controlled phase 2a trial. The randomized trial was launched in September and initially included healthy adults between 18 and 55 years of age as well as individuals 65 years and older. The amended protocol now includes adolescents and teenagers between 12 and 17 years of age. Currently, the study is enrolling participants from the UK and Spain, but J&J expects to soon start enrollment in the U.S., Canada and the Netherlands. In February, the FDA granted an Emergency Use Authorization (EUA) to the company’s single-dose version of its vaccine, but this authorization restricts the use of the vaccine to adults. The EUA was based on findings from the phase 3 ENSEMBLE trial, which showed the vaccine was 66 percent effective at preventing moderate-to-severe COVID-19 approximately four weeks following vaccination.

The University of Oxford is pausing a trial evaluating AstraZeneca’s COVID-19 vaccine in children and teenagers after concerns were raised that the vaccine may be associated with rare cases of blood clotting. Back in February, researchers of the study started to recruit 300 people between the ages of six and 17 years who were to receive the AstraZeneca vaccine or a control meningitis vaccine. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) is now recommending that people under the age of 30 try to get a different vaccine if possible. Previously, the MHRA had said that the benefits of the COVID-19 vaccine outweigh the potential risks. The World Health Organization has also echoed these sentiments. The European Medicines Agency has not identified a causal association between AstraZeneca’s COVID-19 vaccine candidate and blood clots.

A phase 2 study led by the NIH’s National Institute of Allergy and Infectious Diseases is looking to assess the risk of allergic reactions in patients who have received the Moderna and Pfizer/BioNTech COVID-19 vaccines. The trial will be performed across 35 academic allergy research centers in the U.S. and will recruit up to 3,400 adults between 18 and 69 years of age. The majority of participants in the study (60 percent) will have a history of severe allergic reactions or a mast-cell disorder diagnosis. The other 40 percent of the study population will include individuals with no history of allergic reactions or mast-cell disorder. Up to two-thirds of participants in each study group will be women, given that females tend to experience the most severe allergic reactions to the vaccines.

An early-stage NIH trial is investigating the immunogenicity and safety of Moderna’s investigational mRNA-1273.351 vaccine developed to protect against the B.1.351 variant of SARS-CoV-2. The new variant vaccine delivers instructions for making the SARS-CoV-2 spike that includes mutations in the B.1.351 SARS-Cov-2 variant. The phase 1 study plans to enroll up to 210 healthy adults at four sites in the U.S. Moderna says it plans to test mRNA-1273.351 in animal models concurrently with the phase 1 clinical trial. Participants aged 18 years and older in this trial must have already received Moderna’s mRNA-1273 vaccine, but a subgroup of patients between 18 and 55 years of age who have not received a COVID-19 vaccine are also eligible to participate. Study volunteers will be randomly assigned to one of eight cohorts featuring varying doses of the vaccine.

Fred Hutchinson Cancer Research Center’s COVID-19 Prevention Network (CoVPN) has launched a new trial to study the risk of SARS-CoV-2 infection and transmission among college students who have received the Moderna COVID-19 vaccine. Researchers will evaluate whether the mRNA-1273 vaccine, which is authorized for emergency use by the FDA, can prevent SARS-CoV-2 infections, reduce viral load in the nose and reduce viral transmission from vaccinated college students to other people in the community. Researchers hope the study will provide greater insight into whether the currently authorized COVID-19 vaccine prevents symptomatic and severe COVID-19 in adults. The study will also seek to determine whether an individual can become infected following vaccination. The study will include up to 12,000 college students between the ages of 18 and 26 from more than 20 U.S. universities. Participants will be followed over a five-month period. Half of the cohort will be randomized to receive the vaccine at the time of enrollment, and the other half of participants will receive the vaccine approximately four months later. Around 25,500 people who are considered “close contacts” of the study participants will also be invited to participate in the trial so the researchers can examine the rate of viral transmission from vaccinated people.

A COVID-19 vaccine candidate developed by the University of Texas at Austin and Mount Sinai Hospital, is headed for phase 1/2 clinical trials. The candidate, called NDV-HXP-S, was developed using methods similar to those used to develop influenza vaccines. According to the researchers who developed the vaccine, the new candidate can be stored at regular refrigerator temperatures and can be developed faster and cheaper than other leading COVID-19 vaccines. The two-phase study will enroll 210 healthy participants who will receive the vaccine candidate at different doses without adjuvant and at two different doses with an adjuvant. Endpoints will include safety, tolerability and immunogenicity. Following the completion of an interim analysis of the phase 1 data, researchers will then study the vaccine in 250 participants in a phase 2 portion. Approximately one-third of participants in the phase 2 study will be between the ages of 60 and 75 years of age.

Novavax has updated its clinical trial protocols for two ongoing clinical trials of NVX-CoV2373, the company’s COVID-19 vaccine candidate. The update allows participants from the phase 2b South African trial and the pivotal phase 3 UK trial to receive additional injection rounds in crossover arms. Study participants who elect to receive additional injections will receive an additional two-dose regimen of the vaccine if they originally received the placebo or an additional dose of the placebo if they originally received the active vaccine. In the South African trial, participants will receive the vaccine if they had originally received a placebo or a booster dose of the active vaccine if they had received only the active vaccine. Participants will remain blinded to their treatments throughout the trial. Safety and durability of the vaccine will be assessed over a two-year follow-up period.

Bharat Biotech is launching clinical trials to study whether a third dose of Covaxin, the company’s COVID-19 vaccine, is an effective booster shot when administered six months following the second vaccine dose. The Drugs Controller General of India’s subject expert committee gave permission to the company to test this booster shot in an amended phase 2 trial. Only participants who have received 6 micrograms of the vaccine will receive the third dose. According to the company, the 6-microgram dose was chosen because this demonstrated better immune responses. Last month, Bharat presented initial results of its phase 3 trial, which showed Covaxin was 81 percent effective for protecting against COVID-19.

A nanoparticle COVID-19 vaccine developed by the U.S. Army has entered phase 1 clinical research. The vaccine features a flexible approach capable of targeting several SARS-CoV-2 variants and possibly other coronaviruses. The vaccine, dubbed spike ferritin nanoparticle (SpFN), features a multifaced sphere design that reportedly allows for repetitive and ordered presentation of the spike protein to the body’s immune system. Preclinical research shows that SpFN generates robust and broad neutralizing antibody responses against SARS-CoV-2 as well as three variants of the novel coronavirus. A total of 72 healthy adult volunteers between 18 and 55 years of age will be enrolled in the phase 1 study of SpFN. Participants will receive either placebo or the investigational vaccine candidate.