COVID-19 updates
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COVID-19 Vaccines
An analysis of data from four AZ trials (NCT04324606, NCT04400838, NCT04444674, ISRCTN89951424) included 17,177 patients, with 332 developing COVID-19. The analysis found overall efficacy to be 66.7% two weeks or more after the second dose. Vaccine efficacy was 63.1% in patients that received two full doses of the vaccine and 80.7% in patients that received a half dose initially, followed by a full dose for the booster. Exploratory endpoints included efficacy with different dosing intervals. Patients that received a second dose of vaccine at 12-weeks or later had antibody titers 2-fold higher with 81.3% efficacy. Efficacy was 55.1% in patients whose interval between doses was less than six weeks. A single dose of the vaccine demonstrated efficacy of 76% for 90 days in the prevention of symptomatic infection but did not offer protection for asymptomatic infection. A retrospective analysis by Israeli researchers found the Pfizer-BioNTech vaccine to reduce COVID-19 infection by 30% and symptomatic infections by 47% during the first two weeks after the initial vaccination. In days 15-28 after the immunization, all COVID-19 infections are reduced by 75% and symptomatic infections by 85%. A preprint draft, describes a small trial, where patients that had recovered from COVID-19 had a robust increase in antibody titers after the first dose, but a small increase after a second dose. Patients that had not been infected with COVID-19, had a robust increase with both doses. A preprint draft describes how a single dose of either the Pfizer-BioNTech or Moderna vaccine given to patients that recovered from COVID-19 resulted in high levels of antibodies that were effective in neutralizing the B.1.351 (South African) variant. Without the boost in immunity from the vaccine, the patients’ antibody levels were not robust enough to neutralize the variant. Anthony Fauci and Andy Slavitt have stated, the small studies supporting a single vaccine dose are too limited to change The U.S. recommendation for two doses of either vaccine. The CDC analyzed the safety data of the Pfizer-BioNTech or Moderna vaccines after 13,794,904 vaccine doses were given. The incidence of adverse events was 0.05% with the most common being headache, fatigue, and dizziness. Only 9.2% of adverse events were considered serious. The overall rate of anaphylaxis was similar to other vaccines with 4.5 events per million doses. Sanofi and GlaxoSmithKline are initiating a 720 patient, Phase II study (NCT04762680) with a reformulated version of their COVID19 vaccine. A positive trial would lead to a Phase III vaccine in 2Q21. COVID-19 Vaccines
The World Health Organization (WHO) has endorsed the AstraZeneca COVID-19 vaccine and recommends two doses, given eight to 12 weeks apart. Researchers from Pfizer, BioNTech and the University of Texas evaluated the ability of COVID-19 antibodies from 20 serum samples obtained from 15 participants in the pivotal Phase III BNT162b2 trial (NCT04368728) to neutralize the South African SARS-CoV-2 variant (B.1.351 lineage). The serum samples neutralized the original SARS-CoV-2 virus and all mutant viruses tested at titers of 1:40 or greater. The serum samples were about two-thirds weaker in neutralizing the B.1.351 lineage. The researchers concluded that it was unknown how this reduction would affect immunity. Researches from Moderna and National Institute of Allergy and Infectious Diseases evaluated the ability of COVID-19 antibodies from participants in a Phase I mRNA-1273 trial (NCT04283461), to neutralize pseudovirus designed to mimic the original virus, the United Kingdom SARS-CoV-2 variant (B.1.1.7 lineage) and the South African SARS-CoV-2 variant (B.1.351 lineage). There was no decrease in neutralization of the B.1.1.7 lineage compared to neutralization of the original SARS-CoV-2 virus, but a decrease was seen with the B.1.351 lineage. The researchers concluded that it was unknown how this reduction would affect immunity. COVID-19 Anti-inflammatories The 15,000 patient RECOVERY trial (NCT04381936) has several arms testing lopinavir-ritonavir, dexamethasone, hydroxychloroquine, azithromycin, tocilizumab, convalescent plasma, immunoglobulin (IVIG) and the monoclonal antibody combination REGN-COV2. British researchers reported that mortality was 29% in 2,022 patients that received tocilizumab, compared to 33% that received usual care in COVID-19 patients who required oxygen and had evidence of inflammation. 82% of patients in the trial received dexamethasone. Treatment with tocilizumab also resulted in being discharged alive at 28 days (54% vs 47%). The researchers concluded that adding tocilizumab to dexamethasone reduced the risk of death in COVID-19 patients with hypoxia and significant inflammation. COVID-19 Antivirals In an update, the American College of Physician recommend that remdesivir should not be initiated in hospitalized COVID-19 patients receiving mechanical ventilation or extracorporeal membrane oxygenation (ECMO) because the infection has likely progressed to the inflammatory stage of the disease. ACP recommends consideration of remdesivir for five days in hospitalized patients that do not require ventilation or ECMO. Remdesivir may be given for up to ten days 10 days in patients that progress to mechanical ventilation or ECMO that had already started the drug. Vitamin D has been suggested as having immunomodulatory and anti-inflammatory properties, so Brazilian researchers evaluated, whether a single dose would have a beneficial effect on patients with COVID-19.
COVID-19 Vaccines
J&J requested an emergency use authorization (EUA) for its COVID-19 on 2/4/2021, based on the results of the Phase III ENSEMBLE trial. The FDA scheduled a meeting of the Vaccines and Related Biological Products Advisory Committee on 2/26/2021 to review the vaccine. British researchers are going to test the use of different COVID-19 vaccines for the first and second doses. One trial will give the Pfizer-BioNTech vaccine first and follow it with the AstraZeneca vaccine, while another cohort will receive the vaccines in reverse order. An AstraZeneca trial will evaluate the AZ vaccine with the Russian Sputnik V vaccine. A preprint study described the results of an analysis of circulating SARS-CoV-2 viruses, described how the incidence of the B.1.1.7 (U.K.) variant) is growing and expected to become the dominant strain by March 2021. A preprint draft of a subset of 499 patient from a Phase III trial (NCT04400838, ISRCTN15281137.5), found the efficacy of the AstraZeneca COVID-19 vaccine was 75% against B.1.1.7 (U.K. variant) and 84% against original SARS-CoV-2 viruses in preventing symptomatic infection. The vaccine was less efficacious for asymptomatic infection, 27% for B.1.1.7 compared to 75% for original viruses. In an analysis of a 2,000 patient trial, South African researchers found the AstraZeneca COVID-19 vaccine provided a minimal decrease in mild-to-moderate COVID-19 caused by the B.1.351 mutation. South Africa is pausing use of the AZ vaccine, while results are being examined. Researchers plan to examine whether the AZ vaccine will prevent severe COVID-19 caused by the South African mutation (B.1.351). Pakistan’s health minister announced that interim results from the Pakistani cohort enrolled in a 30,000 patient, Phase III trial (NCT04526990) found that CanSino’s COVID-19 vaccine demonstrated 65.7% efficacy in preventing symptomatic cases and a 90.98% success rate in stopping severe disease. Interim results were reported after 101 cases of COVID-19 developed in the trial cohort. COVID-19 Antivirals Merck announced that after reviewing available data, the company has concluded there is a lack of pre-clinical, clinical and safety data to support the use of ivermectin as a treatment for COVID-19. COVID-19 Antibodies The FDA granted an emergency use authorization (EUA) to Lilly’s monoclonal antibody mixture of bamlanivimab and etesevimab, on 2/9/2021, to treat mild to moderate COVID-19 in patients who are high risk for progression to severe COVID-19 The FDA issued an emergency use authorization (EUA) for convalescent plasma, on 8/23/2020, for the treatment of hospitalized patients with COVID-19. The original EUA was granted for any convalescent plasma product collected at FDA registered blood establishments. In February 2021, the FDA narrowed the EUA to high-antibody-titer convalescent plasma. Eligible patients include hospitalized patients with COVID-19 early in the disease course or impaired humoral immunity. The FDA no longer authorizes the use of plasma with low SARS-CoV-2 antibody titers. Fact sheets have been created for health care providers and patients. The Fact Sheet for HCPs has been revised to reflect the changes in the EUA. The documents include dosing instructions and potential adverse effects, such as allergic reactions, transfusion-associated circulatory overload, and transfusion associated lung injury, as well as the potential for transfusion-transmitted infections. COVID-19 Anti-inflammatories Bisindole (VERU-111) binds to and crosslinks the alpha and beta tubulin subunits of microtubules and intermediate filaments of cells resulting in disruption of the cytoskeleton. Veru is developing bisindole for the treatment of castration resistant prostate cancer and triple negative breast cancer. Veru is evaluating bisindole as a treatment for COVID-19 because of antiviral and anti-inflammatory effects.
COVID-19 Vaccines
An interim analysis of data from 11,636 patients participating in four trials (NCT04324606, NCT04400838, NCT04444674, ISRCTN89951424) evaluating AstraZeneca’s COVID-19 vaccine (AZD1222 or ChAdOx1 nCoV-19) found the average efficacy for two dosing regimens of the vaccine to be 70% in preventing COVID-19. Giving a half dose as the first immunization and a full dose four weeks later resulted in 90% efficacy (n=2,741), while giving a full dose at both immunizations resulted in 62% efficacy (n=8,895). No safety issues were found. A preprint draft of a further interim analysis of the four AZ trials (NCT04324606, NCT04400838, NCT04444674, ISRCTN89951424) included 17,177 patients, with 332 developing COVID-19. The analysis found overall efficacy to be 66.7% two weeks or more after the second dose. Vaccine efficacy was 63.1% in patients that received two full doses of the vaccine and 80.7% in patients that received a half dose initially, followed by a full dose for the booster. A single dose of the vaccine demonstrated efficacy of 76% for 90 days in the prevention of symptomatic infection but did not offer protection for asymptomatic infection. Overall, efficacy was 67% with a single dose. Patients that received a second dose of vaccine at 12-weeks (instead of 4-weeks) had antibody titers 2-fold higher with 82.4% efficacy. There were no COVID-19 hospitalizations in the vaccine group, compared to 22 in the placebo group. In a 151 patient, Phase I Australian trial (NCT04405908), Clover’s protein-based COVID-19 vaccine candidate was combined with GSK’s vaccine adjuvant, ASO3 in one cohort and Dynavax’s vaccine adjuvant, CpG 1018 in another cohort. Both vaccines boosted with an adjuvant elicited antibody titers higher than a panel of recovered COVID-19 patients in all age groups. The vaccine without an adjuvant elicited minimal antibody response. The ASO3 adjuvant elicited a higher neutralizing response, but also a higher incidence of adverse events. Clover plans to initiate a Phase II/III trial to evaluate the safety and efficacy of SCB-2019 in combination with Dynavax’s vaccine adjuvant, CpG 1018, in the first half of 2021. The trial is sponsored by CEPI. Clover and GSK discontinued development of Clover’s COVID-19 vaccine in combination with GSK’s vaccine adjuvant, ASO3. GSK will manufacturer up to 100 million doses of CureVac COVID-19 vaccine candidate CVnCoV. GSK and CureVac will also develop a multi-valent vaccine to offer broader protection against COVID-19 mutations. The companies are targeting 2022 for the multi-valent vaccine to be available. Pfizer and BioNtech are receiving help in manufacturing their vaccine. Sanofi agreed to manufacture 125 million doses in a German plant for use in European countries and Novartis has agreed to fill vaccine vials at a Swiss plant. In order to increase vaccine capacity, Moderna, has asked the FDA to approve putting 15 doses in each vial. The same vials are currently filled with 10 doses. Interim results from 21,977 patients enrolled in the 40,000 patient, Russian, Phase III (RESIST) trial (NCT04530396), found that two doses of the Sputnik V vaccine given 21 days apart resulted in 91.6% efficacy based on 78 cases of COVID-19 that developed in the study population (16 cases in the vaccine group vs 62 in the placebo group). The trial population was almost all white, 11% were over 60 and almost 25% had a risk factor for severe disease. Efficacy was stable across all age groups. The most common adverse effects were flu-like illness, injection site reactions, headache, and asthenia. An unpublished and unedited study compared the increase in antibodies for SARS-CoV-2 in seropositive COVID-19 patients to uninfected volunteers. Seropositive patients developed antibody titers that were ten times higher after one dose of Moderna’s or Pfizer’s vaccine compared to the antibody levels attained by the volunteers after two doses. The seropositive patients also had a higher incidence of adverse effects. COVID-19 Anti-Inflammatories French researchers retrospectively examined the results after 7-days in 111 children that progressed to multisystem inflammatory syndrome (MIS-C) from a COVID-19 infection. Fever persisted in 9% of patients that received IVIG and methylprednisolone compared to 51% in the IVIG only group. NIH found insufficient evidence to recommend either for or against the use of tocilizumab or sarilumab for the treatment of COVID-19 in patients who are within 24 hours of admission to the ICU and who require invasive or noninvasive mechanical ventilation or high-flow oxygen, however some members of the advisory panel would administer a single dose of tocilizumab (8 mg/kg of actual body weight, up to 800 mg) in addition to dexamethasone to these patients. NIH recommends against the use of interleukin-6 (IL-6) inhibitors (tocilizumab, sarilumab, siltuximab) for the treatment of COVID-19 patients that do not require ICU-level care or are beyond 24 hours of admission to the ICU even if they require invasive or noninvasive mechanical ventilation or high-flow oxygen. The NIH panel did not exclude use of an IL-6 inhibitor as part of a clinical trial. |
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