COVID-19 Drug Research Roundup
Novavax’s vaccine NVX-CoV2373 is 96.4 percent effective at preventing mild, moderate and severe COVID-19 disease caused by the original strain of SARS-CoV-2, according to a final analysis from a UK phase 3 study. This study included more than 15,000 adults between the ages of 18 to 84. The vaccine was 86.3 percent effective against the UK variant of the novel coronavirus, B.1.1.7, bringing the vaccine’s overall efficacy to 89.7 percent. In contrast, a smaller phase 2b trial from Novavax conducted in South Africa found that the company’s vaccine was 55.4 percent effective in 2,665 HIV-negative participants, many of whom were previously exposed to the South African coronavirus strain. NVX-CoV2373 provided 100 percent protection against severe disease in both the UK and South African trials. Novavax is currently awaiting findings from a U.S./Mexico phase 3 study initiated in December 2020. This trial completed enrollment of 30,000 participants last month. The company expects to have primary results from this trial by the end of March. Data from the U.S. portion of the trial could be used to support filing an Emergency Use Authorization (EUA) application with the FDA. However, Novavax says it first plans to file with the UK Medicines and Healthcare products Regulatory Agency before it seeks an EUA in the U.S. Filing in the UK and the U.S. is expected to begin in the second quarter of 2021.
A recently launched global phase 3 trial is evaluating Medicago’s plant-derived COVID-19 vaccine combined with an adjuvant product from GlaxoSmithKline (GSK). Both companies plan to enroll up to 30,000 participants in this randomized trial. Healthy adults, elderly adults and adults with comorbidities are expected to be included in the final cohort. Researchers will administer two doses of the vaccine candidate 21 days apart. In mid-February, the FDA granted Fast-Track designation to Medicago’s COVID-19 vaccine in combination with GSK’s adjuvant. Medicago recently said it has also started a feasibility study of a vaccine candidate that has been designed to target emerging variants of COVID-19, but specifics about this candidate have yet to be disclosed.
Moderna has dosed its first participants in a phase 1 trial of its next-generation COVID-19 vaccine candidate mRNA-1283, which is being developed as a refrigerator-stable COVID-19 vaccine. If successful, this vaccine could be easier to store, distribute and administer compared with the company’s currently authorized COVID-19 vaccine mRNA-1273, which features much more stringent temperature requirements. The phase 1 trial is evaluating the safety and immunogenicity of the next-generation, two-dose mRNA-1283 vaccine at 10- and 30-microgram doses as well as at a single 100-microgram dose. The vaccine will be compared with Moderna’s authorized mRNA-1273 vaccine. Moderna says it will also evaluate the next-generation vaccine candidate in future studies to determine its safety, immunogenicity and efficacy in seronegative patients. Additionally, the company hopes to assess the vaccine as a booster for previously vaccinated or seropositive patients. Meanwhile, Moderna has launched a study to evaluate its authorized mRNA-1273 COVID-19 vaccine in children between the ages of six months to 11 years. The randomized, placebo-controlled phase 2/3 trial aims to enroll up to 6,750 children in the U.S. and Canada. Last year, Moderna launched a trial to evaluate its vaccine in adolescents aged 12 years and older, but the results of this trial are still pending.
Translate Bio and Sanofi Pasteur have launched a phase 1/2 trial of their co-developed mRNA COVID-19 vaccine MRT5500. Researchers will assess the safety, reactogenicity and immunogenicity associated with the vaccine candidate in up to 415 healthy adults across 13 study sites. Participants in the trial will receive a single dose of the vaccine or two doses administered 21 days apart. Other preclinical studies are currently underway to assess the efficacy of MRT5500, among other mRNA vaccines, in terms of the candidate’s ability to generate neutralizing antibodies against emerging variants of the novel coronavirus.
An Iranian COVID-19 vaccine called COVO Iran Barakat has entered into phase 2 and 3 human clinical trials, according to a recent announcement made by Tehran University of Medical Sciences. The first human injection of the vaccine was performed in the first phase of the trials back in December. Iran has previously said it expects to have the capacity to manufacture up to 3 million doses of the vaccine every month, pending approval. Iran also said it can produce 12 million to 15 million doses of the vaccine by the end of this spring and should be able to increase its manufacturing capacity by 15 million to 20 million doses.
China has granted an emergency use approval to ZF2001, a COVID-19 vaccine manufactured by the Institute of Microbiology of Chinese Academy of Sciences (IMCAS) and Anhui Zhifei Longcom Biopharmaceutical, a unit of Chongqing Zhifei Biological Products. This approval follows approval of two other Chinese COVID-19 vaccines from Sinopharm as well as one from Sinovac and another from CanSino Biologics. Earlier this month, ZF2001 was granted approval for use in Uzbekistan. A study last year found the IMCAS-developed COVID-19 vaccine was safe and induced immune responses in early and mid-stage human trials. The vaccine does have limitations, including its inability to produce many T-cells, which can clear infected cells in the body.
Roche’s global phase 3 REMDACTA trial recently showed that the company’s anti-inflammatory drug Actemra (tocilizumab) does not significantly improve the time to hospital discharge compared with placebo in hospitalized patients with severe COVID-19 pneumonia. The trial, conducted in partnership with Gilead Sciences, pitted Actemra plus Veklury (remdesivir) against placebo plus Veklury with standard of care. In addition to failing to improve time to discharge at up to 28 days, the treatment regimen also failed to meet key secondary endpoints of death, likelihood of progression to mechanical ventilation or death and clinical status. Roche says it will continue to analyze the data from REMDACTA and will publish a full report of the findings in a peer-reviewed journal.
The National Institutes of Health’s ACTIV-3 trial is looking to test Molecular Partners’ and Novartis’ novel antiviral ensovibep in hospitalized patients with mild-to-moderate COVID-19. Molecular Partners has reported preclinical data that suggest the antiviral agent can quickly enter the lungs and rapidly block SARS-CoV-2 to the point of no infectivity or activity. Additionally, the preclinical data suggest ensovibep binds to the spike protein on the novel coronavirus much better than antibodies, all without inducing immune-related side effects. Molecular Partners also plans to test the efficacy and safety of ensovibep in patients with mild-to-moderate COVID-19 in a phase 2 study, as well as in the phase 2/3 EMPATHY trial. The EMPATHY trial is set to enroll up to 2,400 patients. The company also says it will soon evaluate intravenous ensovibep in a phase 1 safety and dose-escalation trial.
A multi-site, outpatient clinical trial from the University of Minnesota Medical School is evaluating whether the generic type 2 diabetes drug metformin can be used as an effective treatment for COVID-19. The study was launched after researchers from the university found that outpatient metformin use reduced the likelihood of hospitalization or death from COVID-19 in computer modeling and observational studies. The trial is recruiting volunteers between 30 and 85 years of age, all of whom have received a positive COVID-19 test within three days of enrollment. All participants will be overweight or obese, both of which are key characteristics associated with worse outcomes with COVID-19. Researchers will also enroll pregnant women, making this one of the first randomized clinical trials for COVID-19 that includes this patient population. Patients in the trial will receive metformin or placebo twice per day for a total of 14 days. At the end of the 14-day treatment period, participants will complete a survey that will assess changes in symptoms.
Germany’s CORAT Therapeutics has received regulatory authorization to study its SARS-CoV-2 neutralizing human antibody COR-101 in a phase 1b/2 trial. In this first-in-human trial, researchers will evaluate COR-101 vs. placebo in up to 45 hospitalized patients with moderate-to-severe COVID-19. Endpoints will include safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and efficacy. Both COR-101 and placebo will be administered intravenously at a single dose in all study cohorts. There will be six initial study centers in Germany, but this will eventually be expanded to up to 15 centers across Europe.
New data from the phase 3 COMET-ICE trial show Vir Biotechnology’s and GlaxoSmithKline’s (GSK) investigational VIR-7831, a SARS-CoV-2 monoclonal antibody, provides an 85 percent reduction in hospitalization or death when given alone as an early treatment in adults with COVID-19. The study, which halted enrollment early due to “evidence of profound efficacy,” included participants who were at high risk of disease progression because of comorbidities and/or age. The recent interim analysis of the COMET-ICE trial included 583 patients who were treated with either VIR-7831 or placebo. Based on the new findings from the study, Vir Biotechnology and GSK are now seeking Emergency Use Authorization for the therapy in the U.S. Another study from Vir Biotechnology and GSK also suggests VIR-7831 features activity against circulating SARS-CoV-2 variants, including those from the UK, Brazil and South Africa. The new data from this study are pending publication in the online preprint server bioRxiv.