The CDC provides advice on myocarditis and pericarditis in adolescents and young adults who received an mRNA COVID-19 vaccine. Most cases have occurred in male patients 16 and older and patients responded well to treatment. The CDC continues to recommend vaccination of all patients 12 years and older due to the greater risk for complications from COVID-19. A preliminary FDA review found reported cases of myocarditis/pericarditis have been consistent with the Pfizer-BioNTech COVID-19 vaccine clinical trials. The reported cases were greater than expected in patients 16 to 24. After the second dose, the incidence is estimated to be 16 cases per million doses. At least 81% of affected patients fully recovered. HHS, CDC and several professional societies published a statement in support of continued vaccination of all eligible patients 12 and older.
Oxford University is examining the safety and efficacy of giving two different COVID-19 vaccines to provide evidence for when the use of two different vaccines is unavoidable and to determine optimal use of the vaccines. A preprint draft provides results from the first phase of the 830 patient, Com-COV trial, where the elicited immune response was measured after different combinations of Comirnaty (Pfizer/BioNTech COVID-19 vaccine) and Vaxzevria (AstraZeneca COVID-19 vaccine) were given 4 weeks apart and antibody levels measured 28-days after the second dose.
A preprint draft provides results from a study examining antibody levels after a delayed second dose or third dose of the AstraZeneca COVID-19 vaccine. Antibody titers were higher with longer intervals. A third dose of the vaccine produced higher antibody titers and T-cell response.
HHS and the FDA are pausing distribution of Lilly’s monoclonal antibody combination bamlanivimab and etesevimab and etesevimab alone, due to concerns over resistance with COVID-19 variants. Distribution of bamlanivimab had been paused in April 2021.
Emricasan is a pan-caspase inhibitor being developed by Histogen for the treatment of nonalcoholic steatohepatitis. Because of emricasan ability to reduce inflammation, Histogen is evaluating the drug for the treatment of COVID-19.
The FDA granted an EUA for tocilizumab (Actemra, Roche) to treat hospitalized adults and pediatric patients two years of age or older, with COVID-19 and who are receiving a systemic corticosteroid and require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
Curevac announced interim data from the 36,500 patient, Phase IIb/III, HERALD trial (NCT04652102), where the mRNA COVID-19 vaccine CVnCo demonstrated 47% efficacy after 134 cases of COVID-19 developed in the European and Latin American study population. An analysis of COVID-19 cases found all but one infection was from COVID-19 variants.
In a pre-print draft of the 28-day, 9,785 patient RECOVERY trial (NCT04381936), treatment with Regeneron’s REGN-COV2 monoclonal antibody combination of casirivimab and imdevimab added to standard-of-care reduced all-cause mortality compared to placebo in hospitalized patients with COVID-19. In the placebo group, mortality was 30% in seronegative patients and 15% in seropositive patients. When all patients were compared regardless of antibody status, there was not a benefit with REGN-COV2 (20% vs 21%). However, in patients that were seronegative (had not developed antibodies), mortality was 24% with REGN-COV2 compared to 30% with placebo. Hospital stay was shorter (13 vs 17 days), the chance of being discharged greater (64% vs 58%) and use of mechanical ventilation or death was lower (30% vs 37%) in the seronegative group of patients.
GSK and Vir announced that in the 29-day, 1,057 patient, Phase III, COMET-ICE trial (NCT04545060), treatment with VIR-7831 reduced the risk for hospitalization or death by 79% compared to placebo in patients with mild to moderate COVID-19 who are at high risk of progression to severe disease.
Tofacitinib (Xeljanz, Pfizer) is a JAK1 and JAK3 inhibitor with partial JAK2 inhibition. It is theorized that JAK inhibition may reduce cytokine storm associated with COVID-19 infection and decrease viral reproduction.
Redhill Biopharm announced that in a 14-day, 40 patient, Phase IIa U.S. trial (NCT04414618), 50% of patients treated with opaganib did not require oxygen compared to 22% with placebo in hospitalized patients with severe COVID-19 pneumonia requiring supplemental oxygen. 86.4% in the opaganib group were discharged by Day 14 compared to 55.6% with placebo. Most patients received dexamethasone and/or remdesivir.
Redhill is evaluating the effect of opaganib on the need for mechanical ventilation in a 475 patient, Phase II/III trial (NCT04467840).
The WHO released simplified names for COVID-19 variants of interest and concern to make it easier to report and talk about these virus mutations in non-scientific reports and articles. The simplified labels use Greek letters to identify a variant. The CDC has added these new designations to its tables of variant classifications and definitions. The WHO lists both the new simple names along with scientific names on its variant tracking page. The current list of variants being tracked by the CDC and WHO include (Pango lineage designation, Region first detected, WHO label):
Researchers from Johnson & Johnson and academia evaluated the efficacy of antibodies from 25 participants in a Phase I/IIa trial of J&J’s Ad26.COV2-S COVID-19 vaccine (NCT04436276) to neutralize COVID-19 variants. While there were decreased neutralization activity, functional activity was maintained for the Alpha variant, Gamma variant and Beta variant.
A preliminary FDA review found reported cases of myocarditis/pericarditis have been consistent with the Pfizer-BioNTech COVID-19 vaccine clinical trials. The reported cases were greater than expected in patients 16 to 24. After the second dose, the incidence is estimated to be 16 cases per million doses. At least 81% of affected patients fully recovered.
The FDA extended the shelf life of the Johnson & Johnson COVID-19 vaccine from 3-months to 4.5 months at refrigeration temperature (2-8 C).
Researchers in Scotland examined COVID-19 cases and found the Delta variant as the dominant variant in the country. The researchers estimated the effectiveness of the Pfizer-BioNTech COVID-19 vaccine to be 92% for the Alpha variant and 73% for the Delta variant. The Astra Zeneca COVID-19 vaccine was 73% effective for the Alpha variant and 60% effective for the Delta variant. A pre-publication draft of a similar study in England found the effectiveness of the Pfizer-BioNTech to be 95% for the Alpha variant and 96% for the Delta variant with the AZ vaccine being 86% effective for the Alpha variant and 92% effective for the Delta variant.
In a 30 patient case series from Johns Hopkins, researchers examined the effect of a third mRNA COVID-19 vaccine dose on transplant patients. Antibody levels were measured before the third dose and most patients had negative antibody levels with six having low levels. The booster dose was given 67 days after the second vaccine dose. Half of the patients received the J&J vaccine, while the rest received one of the mRNA vaccines. All six low antibody level patients developed high antibody titers. In the 24-patient, negative antibody level group, 25% developed high titers, 8% developed low titers and 67% remained negative.
NIH recommends that either Casirivimab plus Imdevimab (Regeneron), Bamlanivimab plus Etesevimab (Lilly) or Sotrovimab (Vir) be used for the treatment of outpatients with mild to moderate COVID-19 who are at high risk of clinical progression. NIH recommends against the use of Bamlanivimab alone, due to resistance from variants, unless the combination products are not available. Use of Bamlanivimab plus Etesevimab may be restricted in areas with high prevalence of the Beta and Gamma variants. NIH also recommends against the use of any monoclonal antibodies in hospitalized patients unless they are part of a clinical trial.
Celltrion announced that in a 28-day, 1,315 patient, Phase III trial (NCT04602000), 3.1% of patients treated with regdanvimab were hospitalized or died compared to 11.1% with placebo in patients with mild-to-moderate COVID-19 at high risk of progressing to severe disease. High risk patients recovered in 9.3 days compared to 14 days with placebo.
Astra Zeneca announced that in the 30-day, 1,121 patient, Phase III STORM CHASER trial (NCT04625972), 3% of patients (23/749) treated with the AZ COVID-19 monoclonal antibody combination, AZD7442 developed symptomatic COVID-19, a non-significant difference compared to 4.6% of patients (17/372) treated with placebo in healthy patients exposed to a patient with COVID-19.
In a pre-publication draft of the 28-day, 520 patient, Phase III, LIVE-AIR trial (NCT04351152), treatment with Humanigen’s lenzilumab improved ventilator-free survival by 54% in the mITT population and by 90% in the ITT population compared to placebo in hospitalized hypoxic COVID-19 patients not requiring invasive mechanical ventilation. In the trial, 93.7% of patients received a corticosteroid, 72.4% received remdesivir, and 69.1% received both. Ventilator-free survival was improved by 92% in patients where lenzilumab was added to both corticosteroids and remdesivir.
Humanigen requested an Emergency Use Authorization (EUA) for lenzilumab for the treatment of patients hospitalized with COVID-19, based on results from the LIVE-AIR trial
Merck has entered an agreement with the U.S. government that if molnupiravir receives an EUA or is approved for the treatment of COVID-19, Merck will supply the U.S. with 1.7 million doses of molnupiravir for $1.2 billion.
The FDA updated the EUA for Regeneron’s monoclonal antibody combination, REGEN-COV. The dose had been lowered to 1,200 mg (600 mg casirivimab and 600 mg imdevimab). REGEN-COV is administered by intravenous infusion but can now be given subcutaneously when intravenous administration is not feasible.
In the 11,558 patient, open-label, convalescent plasma arm of the British RECOVERY trial (NCT04381936), treatment with convalescent plasma did not decrease 28-day mortality compared to usual care (24% in both groups) in patients hospitalized with COVID-19.
In a 10-day, 86 patient, Iranian study, treatment with methylprednisolone 2 mg/kg/day improved the 9-point WHO ordinal scale (0 - uninfected to death 8) compared to dexamethasone 6 mg/day at five days (4.02 vs. 5.21) and 10 days (2.90 vs. 4.71) in hospitalized COVID-19 patients. Methylprednisolone also decreased the length of hospital stay (7.43 vs 10.52 days) and the need for mechanical ventilation (18.2% vs 38.1%). It should be noted the relative dose of methylprednisolone was higher than dexamethasone.
A pre-print draft of a 12,675 patient, British observational study described the effectiveness of COVID-19 vaccines against the B.1.617.2 (Indian) variant. The effectives of the Pfizer-BioNTech COVID-19 vaccine was estimated to be 87.9% after two doses and the AstraZeneca vaccine was estimated at 59.8% efficacy in a cohort of 1,054 patients with an infection with the B.1.617.2 variant.
The CDC provides advice on myocarditis and pericarditis in adolescents and young adults who received an mRNA COVID-19 vaccine. Most cases have occurred in male patients 16 and older and patients responded well to treatment. The CDC continues to recommend vaccination of all patients 12 years and older due to the greater risk for complications from COVID-19.
An analysis of patients with immune-mediated inflammatory diseases who were receiving immunomodulatory treatments found that use of methotrexate decreased the immune response from the Pfizer-BioNTech COVID-19 vaccine. Over 90% of patients that were receiving a TNF blocker achieved a robust antibody response compared to only 62.2% of patients that were receiving methotrexate that achieved an adequate response.
The FDA may not review additional COVID-19 vaccines for emergency use if the sponsoring company is not already in discussions with the FDA. Novavax, Medicago and Astra Zeneca have discussed approval with the FDA. Other vaccine developers would need to seek full authorization.
In a 2,260 patient, Phase III trial (NCT04368728), no cases of COVID-19 developed in patients immunized with the Pfizer-BioNTech COVID-19 vaccine compared to 16 cases in the placebo group for 100% efficacy in patients 12 to 15.
In a 77-day, 40,382 patient, Phase III trial (NCT04510207), efficacy was estimated to be 72.8% with Sinopharm’s WIV04 COVID-19 vaccine and 78.1% with the HB02 vaccine in healthy adults in the United Arab Emirates and Bahrain.
HHS has paused distribution of Lilly’s monoclonal antibody combination bamlanivimab and etesevimab in Illinois and Massachusetts, Arizona, California, Florida, Indiana, Oregon and Washington because the combined incidence of the P.1 variant (Brazil) and B.1.351 variant (South Africa) exceeds 10% of COVID-19 cases. In vitro data suggest that bamlanivimab and etesevimab administered together are not active against these variants. HHS recommended Regeneron’s REGN-COV2 a combination of casirivimab and imdevimab be used when a monoclonal antibody is needed in these states.
The FDA granted an Emergency Use Authorization (EUA) to sotrovimab (VIR-7831) for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with COVID-19, who are at high risk for progression to a severe infection. Healthcare providers should review the Fact Sheet for information on the authorized use of casirivimab and imdevimab and mandatory requirements of the EUA. Please see the FDA Letter of Authorization, Fact Sheet for Healthcare Providers, and Fact Sheet for Patients, Parents, and Caregivers.
In the 28-day, 146 patient, open-label, Phase III, STOIC trial (NCT04416399), 3% of patients treated with inhaled budesonide added to usual care required urgent care or hospitalization compared to 15% with usual care alone in outpatients with COVID-19. Clinical recovery was also one-day less with budesonide.
In the 30-day, 4,488 patient, Phase III, COLCORONA trial (NCT04322682), treatment with colchicine did not reduce hospitalizations or mortality compared to placebo in outpatients with COVID-19 diagnosed by PCR testing or clinical criteria, who were at least 40 years old and had at least one risk factor for more severe disease. Among the 4,159 patients with PCR confirmed infection there was a small benefit with colchicine with 4.6% of patients requiring hospitalization or dying compared to 6% with placebo.
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