J&J announced that in the 43,783 patient, Phase III, ENSEMBLE trial (NCT04505722), a single immunization with their COVID-19 vaccine resulted in 66% efficacy based on 468 cases of moderate to severe COVID-19 that developed in the study population. There were regional variations with efficacy measured as 72% in the United States (44% of the study population), 66% in Latin America (41% of the population) and 57% in South Africa (15% of the population). The vaccine was 85% effective in preventing severe disease. 34% of the study population was over the age of 60. The study population also included 19% who identified as Black or African American, 45% Hispanic or Latino, 9% Native American and 3% Asian. 41% of the population had a risk factor to develop severe COVID-19. J&J stated the vaccine was well tolerated but did not provide details of adverse events.
Novavax announced that in a 15,000 patient, Phase III trial (NCT04583995), two doses of NVX-CoV2373 given 21-days apart resulted in 89.3% efficacy based on 62 cases of moderate to severe COVID-19 that developed in the United Kingdom study population. Efficacy was 95.6% against the original COVID-19 strain and 85.6% against the UK variant strain.
Novavax announced that in a 4,400 patient, Phase IIb (NCT04533399) two doses of NVX-CoV2373 given 21-days apart resulted in 60% efficacy based on 44 cases of moderate to severe COVID-19 that developed in the South African study population. Efficacy was decreased due to the South Africa variant strain. In an analysis of 27 of the COVID-19 cases, the mutated virus was present in 92.6% of cases.
NIH announced the initiation of a 30,000 patient, Phase III, PREVENT-19 trial (NCT04611802) to evaluate the safety and efficacy of NVX-CoV2373, a COVID-19 vaccine from Novavax. Two vaccinations will be given 21-days apart. In late January 2021, Novovax announced they had enrolled over 16,000 patients in a 30,000 patient PREVENT-19 trial in the U.S. and Mexico.
Novovax initiated development of a vaccine to combat COVID-19 variants in January 2021 and plans to use the candidate in a bivalent vaccine or booster vaccine.
Lilly announced that in the 29-day, 1,035 patent, Phase III portion of the BLAZE-1 trial (NCT04427501), 2.1% of patients treated with bamlanivimab 2800 mg plus etesevimab 2800 mg experienced the primary endpoint of COVID-19 related hospitalizations or death compared to 7% that received placebo in patients with mild to moderate COVID-19 who were at high risk for progressing to severe COVID-19 and/or hospitalization. No deaths occurred in the combination treatment group compared to ten deaths in the placebo group.
Lilly is comparing bamlanivimab alone, and bamlanivimab and etesevimab together, at various doses, versus placebo in the reduction of viral load in the 7-day, 1,000 patient, Phase II BLAZE-4 trial (NCT04634409). Initial data suggests that lower doses of bamlanivimab and etesevimab may be effective. BLAZE-4 will also evaluate the combination of Lilly’s bamlanivimab in combination with Vir’s and GSK’s VIR-7831.
Regeneron announced preliminary results from 409 patients enrolled in an NIAID sponsored, 2,000 patient, Phase III trial (NCT04452318), where treatment with casirivimab and imdevimab prevented symptomatic infection in all 186 patients compared to 8 symptomatic infections in 223 patients who received placebo in COVID-19 negative patients exposed to a COVID-19 patient in the same household. A combination of symptomatic and asymptomatic infection developed in 10/186 that received casirivimab and imdevimab compared to 23/223 that received placebo.
An unpublished and unedited invitro study that tested the ability of antibodies to neutralize pseudoviruses with new variant mutations of COVID-19 found that while there was some decrease in activity with convalescent plasma from recovered patients and vaccinated patients, the antibodies still were able to neutralize the pseudoviruses. The pseudoviruses were resistant to the activity of single monoclonal antibodies, but when two antibodies with different sites of action were combined, neutalization activity was maintained.
An unpublished and unedited invitro study that tested the antiviral effects of plitidepsin, ralimetinib and remdesivir on early SARS-CoV-2 and the B.1.1.7 variant found similar activity with both viral strains.
The CDC released some updates on COVID-19 vaccines.
Lilly announced that in the 965 patient, Phase III, BLAZE-2 prevention trial (NCT04497987), fewer patients and staff that received bamlanivimab 4,200 mg developed COVID-19 than patients and staff who received placebo in 299 residents and 666 staff at skilled nursing and assisted living facilities. A pre-specified subgroup of residents had an 80% lower risk of testing positive for COVID-19 compared to residents in the same facility that received placebo. No deaths were reported in residents that received bamlanivimab compared to four that received placebo.
Final results from 577 patients enrolled in the 11-day, dose-ranging, Phase II portion of the BLAZE-1 trial (NCT04427501), that received bamlanivimab alone (700mg, 2,800mg or 7000mg) did not decrease viral load by day 11 compared to placebo in non-hospitalized patients with mild to moderate COVID-19. The full data set for the placebo groups was not available for the interim analysis, which may explain the difference in outcomes with the final analysis. However, the combination of bamlanivimab 2800 mg and etesevimab 2800 mg decreased the viral load compared to placebo. The combination group was also the only one that had a significant decrease in COVID-19 related hospitalizations or emergency department visits at day 29.
In the 15-day, 129 patient, Phase III, TOCIBRAS trial (NCT04403685), treatment with tocilizumab did not reduce a composite of death or mechanical ventilation (28% vs 20%) compared to placebo in patients with COVID-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). At 15-days, mortality was higher with tocilizumab compared to placebo (17% vs 3%), but the difference was no longer significant at day 29.
In an 805 patient, Phase I/IIa trial (NCT04436276), JNJ’s COVID-19 vaccine, Ad26.COV2.S, elicited neutralizing antibodies in two cohorts of patients (18-55 and 65 or older). 29 days after the first dose, neutralizing-antibodies were produced in 99% of patients in the younger cohort and 96% of patients in the older cohort. Antibody titers continued to increase at day 57. A higher dose of the vaccine elicited more antibodies than the lower dose. Some patients received a second dose of the vaccine, which resulted in even higher antibody levels. Longer term data comparing one-dose and two-dose regimens will be reported in the future. The most frequent adverse events were injection site pain, fatigue, headache and myalgia. Adverse events were less common in older patients than younger patients. JNJ is evaluating Ad26.COV2.S in two Phase III trial. A one-dose regimen is used in the ENSEMBLE trial (NCT04505722) and a two-dose regimen is used in the ENSEMBLE-2 trial NCT04614948)
Celltrion is evaluating regdanvimab (CT-P59) in the treatment of mild-to-moderate COVID-19. Regdanvimab is a neutralizing monoclonal antibody targeting SARS-CoV-2.
A retrospective review (NCT04338360) examined outcomes from 3,082 hospitalized COVID-19 patients who received convalescent plasma. At 30 days, mortality was 22.3% in patients that received convalescent plasma with high antibody titers, 27.4% with medium titers and 29.6% with low titers. An improvement in mortality was only significant in patients who didn't receive mechanical ventilation. Patients that received convalescent plasma within three days of a positive test had lower mortality than those who received it later.
NIH found insufficient evidence to recommend either for or against the use of ivermectin for the treatment of COVID-19. The NIH panel recommends well-designed, adequately powered studies to determine the safety and efficacy of ivermectin to treat COVID-19, since current trials have incomplete data or flawed designs.
In an unpublished and unedited report, researchers describe how antibodies in serum from 20 people, who had received two doses of the Pfizer-BioNTech COVID-19 vaccine, neutralized SARS-CoV-2 with and without the mutation (N501Y) with similar efficacy. The N501Y mutation has been identified as causing a faster spread of the disease in the U.K. It has also been identified in the U.S.
The FDA approved use of any full extra doses contained in the vials of the Moderna COVID-19 vaccine. Because the vaccine does not contain preservative, the FDA advises not to pool excess vaccine from multiple vials to create one dose.
CureVac has signed an agreement with Bayer to help develop, distribute and market its COVID-19 vaccine candidate CVnCoV.
Brazilian researchers originally reported 78% efficacy for the Sinovac Biotech’s COVID-19 vaccine, but lowered the efficacy to 50.4%, when very mild cases were included in the analysis. Interim data from Brazil and Turkey have given different efficacy calculations, so the true protection of the vaccine is unclear.
In an unpublished and unedited report of a 21-day, 803 patient, Phase IV, REMAP-COVID trial (NCT02735707), in-hospital mortality was 28% with tocilizumab (n = 353), 22% with sarilumab (n = 48), and 36% with standard care (n = 401) in patients with critical COVID-19 receiving organ support in intensive care. The number of organ support-free days were 10 for tocilizumab, 11 for sarilumab and none for standard of care. A third of patients received remdesivir and 80% received a corticosteroid. REMAP-COVID is a sub-study of the REMAP-CAP trial.
The United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) has issued an emergency authorization for AstraZeneca’s COVID-19 vaccine. Immunization with the vaccine is expected to begin in early January 2021. AZ’s vaccine will probably not be available in the U.S. until April 2021.
NIH announced the initiation of a 30,000 patient, Phase III, trial (NCT04611802) to evaluate the safety and efficacy of NVX-CoV2373, a COVID-19 vaccine from Novavax. Two vaccinations will be given 21-days apart. Due to difficulties in scaling up vaccine manufacturing, the initiation of the trial was delayed twice.
Sinopharm announced the efficacy of its COVID-19 vaccine was 79% in a Phase III trial.
In the NIAID funded, 30,420 patient, Phase III, COVE trial (NCT04470427), mRNA-1273 administered as two 100 mcg immunizations given 28 days apart resulted in 94.1% efficacy based on 196 cases of COVID-19 that developed in the study population. 24.8% of the study population was over the age of 65 and 16.7% were under 65 with increased risk for severe COVID-19 due to co-morbidities. The study population also included 10.2% who identified as Black or African American and 20.5% Hispanic or Latino. The most common adverse effects were injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site. There was a slight increase in frequency and severity of adverse effects after the second immunization.
Regeneron is evaluating the combination of casirivimab and imdevimab in a Phase I/II trial as a treatment of COVID-19 in 6,900 hospitalized patients (NCT04426695). Regeneron discontinued enrollment of hospitalized COVID-19 patients that required high-flow oxygen or mechanical ventilation on 10/30/2020 at the recommendation of the independent data monitoring committee (IDMC) due to a potential safety signal and an unfavorable risk/benefit profile. The IDMC recommended continuing enrollment of hospitalized patients requiring either no or low-flow oxygen. Regeneron announced interim data from patients enrolled in a Phase I/II trial (NCT04426695), where treatment with casirivimab and imdevimab lowered the risk for death or receiving mechanical ventilation compared to placebo in 217 hospitalized seronegative COVID-19 patients requiring low-flow oxygen. A reduction in death or receiving mechanical ventilation was not found in 270 seropositive patients. Remdesivir was used concomitantly in 67% of patients and 74% received systemic corticosteroids.
In a 15-day, 160 patient trial (NCT04479163), 16% of mild COVID-19 patients treated with high-antibody-titer convalescent plasma (IgG above 1:1000 against SARS-CoV-2 spike protein) progressed to severe COVID-19 compared to 31% with placebo. Argentinian patients with mild COVID-19 were enrolled if they were 75 or older with or without risk factors for severe COVID-19 or between 65-74 with at least one risk factor. Convalescent plasma was administered within 72 hours after the onset of mild COVID-19 symptoms. Enrollment in the trial was stopped early due to a reduction in available patients. The trial was originally designed to enroll 210 patients.
Redhill Biopharm is evaluating opaganib as a treatment for COVID-19. Opaganib is an orally administered, sphingosine kinase-2 (SK2) selective inhibitor. The drug has both anti-inflammatory and antiviral activity, which targets viral replication, potentially minimizing the likelihood of viral resistance. Opaganib is being developed for the treatment of cholangiocarcinoma and prostate cancer. Opaganib demonstrated antiviral activity against SARS-CoV-2 in-vitro.
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