COVID-19 Drug Research Roundup

COVID-19 Therapies:

TRV027, a novel AT1 receptor-selective agonist developed by clinical stage biopharmaceutical company Trevena, has been selected to become part of an international phase 2/3 COVID-19 trial. The primary Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) is a multisite adaptive trial conducted by a global network of institutions, research facilities and clinicians. The trial is currently evaluating several drugs to identify effective treatments that can reduce mortality, minimize intensive care unit admissions and reduce morbidity in patients with severe COVID-19. In the phase 2/3 REMAP-CAP COVID-19 ACE2 RAS Modulation Domain trial, researchers will specifically examine treatments targeting the renin-angiotensin system (RAS). Study investigators will examine if RAS modulation averts multiorgan failure and reduces mortality in hospitalized patients infected with the novel coronavirus. Up to four active treatments have been included in the study protocol. Between 200 and 300 participants will be enrolled in each treatment arm. In the TRV027 group, participants will be given the candidate alongside an ACE inhibitor.

Patients have started to enroll in the National Institutes of Health’s (NIH) phase 2/3 ACTIV-2 trial, which is investigating SAB Biotherapeutics’ SAB-185. The company’s novel SAB-185 candidate will be administered to nonhospitalized patients with mild or moderate COVID-19. Preclinical studies show SAB-185 can neutralize live SARS-CoV-2, the coronavirus responsible for COVID-19, at titers higher than that seen with convalescent plasma. This part of the ACTIV-2 master protocol will allow investigators to assess SAB-185 in a small group of nonhospitalized patients before the therapy is progressed to a larger population. A total of 110 patients with mild or moderate COVID-19 who are at risk for disease progression will be enrolled in the blinded phase 2 study. Participants in the initial trial will be randomized to either intravenous SAB-185, another treatment or placebo. If the investigational agent shows promise and is not associated with any safety concerns, it will then progress into phase 3 testing. The phase 3 trial will enroll 421 additional patients in the active treatment group and another 421 patients in the placebo arm. Other treatments that will be assessed in this study include Brii Biosciences’ antibodies BRII-196 and BRII-198, Synairgen’s SNG001, AstraZeneca’s AZD7442 and Sagent Pharmaceuticals’ Camostat mesilate.

The NIH’s new ACTIVE-3 Critical Care trial has started enrolling hospitalized patients with life-threatening COVID-19, including patients who have developed acute respiratory failure. The randomized, placebo-controlled trial will start by investigating the efficacy and safety of Zyesami, a therapy from NeuroRx consisting of aviptadil acetate, as well as Gilead Sciences’ remdesivir. Both therapies will be tested in combination or alone in a group of hospitalized patients with COVID-19 and Acute Respiratory Distress Syndrome (ARDS). Currently, the investigators plan to enroll an initial cohort of 40 patients at sites across the U.S. A larger group of patients will be enrolled if no safety concerns are found in the initial cohort. Several sub-studies are currently in the works for the ACTIVE-3 Critical Care trial. Each of these sub-studies will enroll up to 620 participants, all of whom will be randomized to either an investigational agent or placebo.

Relief Therapeutics and AdVita Lifescience are teaming up in a new phase 2 trial to investigate whether Relief’s inhaled RLF-100 (aviptadil) can prevent COVID-19-related ARDS. RLF-100 is a synthetic vasoactive intestinal peptide that is currently being developed by NeuroRx under the brand name Zyesami. The new randomized phase 2 trial plans to enroll 80 Swiss patients with COVID-19. Patients will be randomly assigned to either RLF-100 or placebo in addition to standard of care. Researchers will investigate the time it takes for patients to show clinical improvement from the point of hospitalization. The limit set for this primary endpoint is 28 days. The first patient has already been enrolled in the study. Relief says that it expects to initiate another European phase 2 dose-finding study of inhaled RLF-100 in patients with pulmonary sarcoidosis.

Austria’s Marinomed Biotech says its seaweed-based sulfated polymer therapy, Carragelose, was able to inactivate emerging and rapidly spreading SARS-CoV2 variants in recent tests. The in vitro tests involved four lentiviruses pseudotyped with the wild-type SARS-CoV-2 spike protein or one of the three highly infectious COVID-19 variants (B.1.1.7, B1.351 and P1). In the in vitro study, Carragelose effectively inactivated all four forms of the virus at concentrations well below 5 µg/ml. According to the company, the nasal sprays that contain Carragelose feature a drug concentration of 1.2 mg/ml, which is a dose that’s approximately 200-fold higher than that shown to be effective in these new in vitro tests. The therapy also demonstrated similar efficacy against the B1.1.7 and B1.351 variants in independent testing conducted at a virological institute of the University Hospital Erlangen in Germany. Marinomed plans to soon publish the data from these tests in a peer-reviewed journal.

COVID-19 Vaccines:

Biotechnology company INOVIO is planning to launch a phase 3 study of INO-4800, its COVID-19 vaccine candidate, which will be conducted outside the U.S. The decision to conduct trial outside the U.S. comes after the Department of Defense (DoD) announced it was going to discontinue funding for the company’s phase 3 trial, given the increasing availability of other authorized COVID-19 vaccines. Ultimately, the DoD decision is reportedly not a reflection of the available clinical trial data on the vaccine. While previous study data show INO-4800 may be effective against some COVID-19 variants, these findings did not stop the U.S. government from withdrawing its financial support for the company’s late-stage trial. The DoD will continue to provide funding for INOVIO’s phase 2 segment of a INO-4800 trial. In conjunction with the ex-U.S. trial, INOVIO will continue to assess INO-4802, the company’s pan-COVID variant vaccine, against current and future coronavirus variants. Additionally, future studies will evaluate the boosting capabilities of INO-4800.

Biological E. says it plans to launch a phase 3 trial of a COVID-19 subunit vaccine candidate after an expert committee of India’s drug regulator approved the study. The Indian vaccine features an antigen developed by scientists at the Texas Children’s Hospital Center for Vaccine Development. Also, the vaccine candidate contains CpG 1018TM, an advanced adjuvant from Dynavax Technologies. Prior data from a phase 1/2 study show the vaccine is safe, well-tolerated and immunogenetic. The new late-stage trial will be conducted across 15 sites in India and will evaluate the immunogenicity and safety of the vaccine. Researchers will also look to determine if the vaccine protects against COVID-19. Approximately 1,268 healthy participants between 18 and 80 years of age will be enrolled. According to Biological E., this study will be part of a larger phase 3 study conducted across sites in other countries.