In a retrospective review of 39,156 asymptomatic patients, in the Mayo Clinic Health System, who were tested for COVID-19 for an upcoming procedure, 1.4% of vaccinated patients tested positive compared to 3.2% of unvaccinated patients for an 80% reduction in the development of asymptomatic COVID-19 with the vaccine.
CDC researchers analyzed results of COVID-19 tests from 3,950 health care workers and first responders to estimate real-world effectiveness of the COVID-19 mRNA vaccines. Vaccine effectiveness was found to be 80% after one immunization and 90% in fully vaccinated individuals.
Lilly, Vir and GSK announced that in the seven-day, Phase II, BLAZE-4 trial (NCT04634409), treatment with bamlanivimab plus VIR-7831 reduced viral load compared to placebo in low-risk adult patients with mild to moderate COVID-19.
Humanigen announced that in a 28-day, 520 patient, Phase III trial (NCT04351152), 15.6% of patients treated with lenzilumab died or required a ventilator compared to 22.1% with placebo in hospitalized hypoxic COVID-19 patients not requiring invasive mechanical ventilation. In the trial, 88% of patients received a corticosteroid, 62% received remdesivir, and 57% received both.
Fluvoxamine, a selective serotonin reuptake inhibitor and sigma-1 receptor (S1R) agonist, approved for the treatment of obsessive-compulsive disorder, is being evaluated for the treatment of COVID-19. Inhibiting S1R decreases cytokine production through its interaction with the endoplasmic reticulum stress sensor inositol-requiring enzyme 1alpha (IRE1). The decrease in cytokines reduces the inflammatory response, which diminishes progression of COVID-19.
On 3/24/2021, AstraZeneca announced that in a 32,449 patient, Phase III, BARDA sponsored U.S. trial (NCT04516746), two doses of AstraZeneca’s COVID-19 vaccine, given 4-weeks apart, had efficacy of 76% with 100% efficacy at preventing severe disease and hospitalizations. Efficacy was calculated after the development of 190 cases of COVID-19. Vaccine efficacy was consistent across ethnicity and age. 20% of patients were older than 65 years and efficacy was 85% for these patients. In the trial 79% of patients were white, 8% black, 4% native American, 4% Asian, and 22% Hispanic. Almost 60% had risk factors for progression to severe COVID-19.
Some countries have expressed concern for an increased risk for thromboembolic events with the AstraZeneca COVID-19 vaccine.
Researchers tested serum samples from 20 acutely ill COVID-19 patients, 20 recovered patients and 14 patients that had received the Moderna COVID-19 vaccine. All samples demonstrated an ability to neutralize the B.1.1.7 (British) variant.
A preprint draft of a study examining data from 84 pregnant, 31 lactating, and 16 non-pregnant patients found the vaccine response was equivalent for pregnant and lactating women compared to non-pregnant women. Further the immune transfer to neonates occurred via placental and breastmilk.
Three letters to the editor were published in the New England Journal of Medicine describing the effectiveness of the COVID-19 mRNA vaccines in healthcare settings.
The FDA revised the health care provider fact sheets to include information on SARS-CoV-2 variants susceptibility to the Lilly and Regeneron monoclonal antibodies that have an Emergency Use Authorization for COVID-19. The fact sheets include information on susceptibilities and potential resistance that may decrease the effectiveness of the antibodies.
The U.S. government will stop distributing bamlanivimab as a single antibody therapy for COVID-19 due to resistance by COVID-19 variants. The combination of bamlanivimab and etesevimab will continue to be distributed because the combination has retained activity against these variants. Healthcare sites with supplies of bamlanivimab can order etesevimab alone to pair with bamlanivimab.
Regeneron announced that in a 29-day, 4,567 patient, Phase III trial (NCT04425629), 1% of patients treated with 1,200mg of the combination of casirivimab with imdevimab progressed to hospitalization or death compared to 3.2% with placebo in high-risk COVID-19 outpatients. Treatment with 2,400 mg of the monoclonal combination resulted in 1.3% of patients progressing to hospitalization or death compared to 4.6% with placebo
In a retrospective review of data from 412 hospitalized patients with COVID-19, 36% of patients receiving aspirin progressed to mechanical ventilation compared to 48% that did not receive aspirin. A multivariable adjustment found a 44% reduced risk for mechanical ventilation with aspirin without an increased risk for major bleeding.
In a 14-day, 39 patient, Phase II trial (NCT04399980, NCT04463004, and NCT04492514), treatment with mavrilimumab (n=21) did not decrease morbidity or the need for supplemental oxygen compared to placebo (n=19) in non-ventilated hospitalized COVID-19 patients with hypoxemia, and a C-reactive protein concentration of 5 mg/dL or greater.
In a retrospective review of 2,483 consecutive patients with severe COVID-19, 342 patients received remdesivir with 184 also receiving corticosteroids. Treatment with remdesivir resulted in a decrease in time to clinical improvement (5 vs 7 days). Mortality had a non-significant decrease (7.7% vs 14%), which was not affected by use of corticosteroids. The patient population was 80% non-white, compared to 30% to 47% in clinical trials.
Researchers at the Icahn School of Medicine compared the antibody response to the Pfizer-BioNTech and Moderna COVID-19 vaccines in 43 recovered COVID-19 patients to 67 healthy volunteers. The seronegative patients had a low, but variable response after the first vaccination, while the seropositive patients had antibody titers that were 10 to 45 times higher. After the second dose there was a three-fold increase in healthy patients, but no increase in recovered patients.
The CDC analyzed surveillance data from 30,494 patients who were vaccinated with either the Pfizer-BioNTech or Moderna COVID-19 vaccines during pregnancy and found the rates of complications were not significantly different from those of unvaccinated pregnant women.
Novavax announced that in a 15,000 patient, Phase III trial (NCT04583995), two doses of NVX-CoV2373 given 21-days apart resulted in 89.7% efficacy based on 106 cases of moderate to severe COVID-19 that developed in the United Kingdom study population. Five cases of severe disease occurred, and all were in the placebo group. Efficacy was 96.4% against the original COVID-19 strain and 86.3% against the B.1.1.7 (UK) variant.
Novavax announced that in a 2,905 patient, Phase IIb trial (NCT04533399), where two doses of the Novavax COVID-19 vaccine given 21-days apart resulted in 48.6% efficacy based on 147 cases of moderate to severe COVID-19. Five cases of severe disease occurred, and all were in the placebo group. Efficacy was 55.4% among HIV negative patients. The trial population included 240 medically stable, HIV-positive adults. Most cases of COVID-19 were the B.1.351 (South African) variant.
Researchers at Johns Hopkins analyzed a convenience sample of 436 transplant patients who were immunized with the Moderna or Pfizer COVID-19 vaccines and detected an antibody response about three weeks after the first immunization in only 17% of patients. Patients were more likely to develop antibodies if they were younger or received the Moderna vaccine. Patients were less likely to show an antibody response if they were receiving anti–metabolite maintenance immunosuppression (mycophenolate or azathioprine).
Researchers from Yale and the CDC analyzed COVID-19 vaccine efficacy in 463 nursing home residents during outbreaks at two Connecticut skilled nursing facilities. Vaccine efficacy was measured from 14 days after the first dose through seven days after the second, because there was not enough follow-up data to determine the impact of full vaccination. The researchers found the vaccines to be as effective as in the general adult population.
Sanofi has signed an agreement with Translate Bio for an mRNA vaccine. Sanofi and Translate Bio are evaluating the COVID-19 vaccine, MRT5500 in a 415 patient, Phase I/II trial with results expected in 3Q21.
In a 2,026 patient, South-African, Phase I/II trial (NCT04444674), 2.5% of patients that received the AstraZeneca COVID-19 vaccine became infected with COVID-19 compared to 3.2% with placebo for a vaccine efficacy of 21.9% in HIV negative adults. 92.9% of COVID-19 infections were caused by the B.1.351 (South African) variant. Vaccine efficacy against the B.1.351 variant was 10.4%. The researchers also tested antibodies from 25 patients and found that vaccine recipients had no neutralization activity against the B.1.351 variant
Lilly announced results from a 796 patient cohort that compared a lower dose of bamlanivimab and etesevimab in the BLAZE-1 trial (NCT04427501), where 0.8% of patients treated with bamlanivimab 700 mg and etesevimab 1400 mg experienced the primary endpoint of COVID-19 related hospitalizations or death compared to 5.8% that received placebo.
GSK and Vir announced that in an interim analysis of data from 583 patients enrolled in the 1,300 patient, Phase III, COMET-ICE trial (NCT04545060), treatment with VIR-7831 reduced the risk for hospitalization or death by 85% compared to placebo in patients with mild to moderate COVID-19 who are at high risk of progression to severe disease. Due to the magnitude of benefit, the Independent Data Monitoring Committee (IDMC) recommended stopping the trial. Based on results from COMET-ICE, GSK and VIR plan to request an emergency use authorization (EUA) for VIR-7831.
Roche announced that in the 28-day, 450 patient, Phase III REMDACTA trial (NCT04409262), adding tocilizumab to remdesivir did not decrease time to hospital discharge compared to remdesivir alone in patient with severe COVID-19. The addition of tocilizumab also did not improve clinical status, decrease mortality, or decrease the need for mechanical ventilation.
In a preprint draft of a 108,851 patient, British trial, efficacy in preventing COVID-19 was 60-70% after one dose of the Pfizer-BioNTech vaccine and 85-90% after two doses. The AstraZeneca COVID-19 vaccine was 60-73% efficacious after one dose. Data was not available to determine efficacy after two doses of the AZ vaccine. Both vaccines were effective in reducing hospitalizations.
Physicians at Massachusetts General Hospital describe delayed cutaneous reactions in 12 patients, who were given the Moderna COVID-19 vaccine. The reactions happened around eight days after the initial immunization and lasted about six days. All patients received their second dose of vaccine and six of the patients developed a second reaction within two days. While the cutaneous reaction is rare, it is more likely to be seen during a mass vaccination campaign, due to the large number of vaccinations.
A preprint draft describes a 4,387 patient, Phase IIb trial (NCT04533399), where two doses of the Novavax COVID-19 vaccine given 21-days apart resulted in 49.4% efficacy based on 44 cases of moderate to severe COVID-19 that developed in a subpopulation of 2,684 patients that were seronegative in a South African study population. This population had both HIV positive and negative patients. Efficacy was 60.1% among only HIV negative patients. Genome sequencing of 41 patients found the South African variant (B.1.351) was present in 92.7% of cases. A post-hoc analysis found that vaccine efficacy against B.1.351 was 51.0%. Prior infection with the presumptive original SARS CoV-2 did provide protection in the placebo group or additional benefit in the vaccine group.
The CDC has provided clinical considerations for the Pfizer-BioNTech, Moderna and Johnson & Johnson COVID-19 vaccines.
Merck announced results from a secondary endpoint in a preliminary report from 182 patients enrolled in a Phase IIa trial (NCT04405570), where 24% of patients treated with molnupiravir achieved a negative cell culture on day five compared to none that received placebo in adult outpatients with symptomatic COVID-19. Merck plans a full presentation of trial results at a future meeting.
CytoDyn announced that in a 28-day, 390 patient, Phase IIb/III trial (NCT04347239), treatment with leronlimab did not decrease mortality compared to placebo in patients with severe or critical COVID-19. However, leronlimab did decrease mortality and hospital duration in a subset of patients receiving mechanical ventilation. An age adjusted analysis also found a mortality decease in the subset of patients under 65.
In the 21-day, 400 patient, Phase III, EPIC trial (NCT04405843), a five-day course of ivermectin did not reduce the time to resolution of symptoms compared to placebo in patients with mild COVID-19.
NIH discontinued the 15-day, 900 patient, Phase III, C3PO trial (NCT04355767) after 511 patients were enrolled, when an interim analysis by the independent data and safety monitoring board did not find that treatment with convalescent plasma reduced emergency treatment, hospitalization or death in patients with mild-to-moderate COVID-19.
VIR-7831 is being evaluated as part of the NIH sponsored, 90-day, 10,000 patient, Phase III, ACTIV-3 trial (NCT04501978) to determine whether adding the monoclonal antibody to remdesivir improved clinical status. NIH closed enrollment of patients in the VIR-7831 arm of the trial due to concerns by the data and safety monitoring board on the magnitude of potential benefit after an interim analysis of data from 344 patients.
The combination of BRII-196 and BRII-198 are being evaluated as part of the NIH sponsored, 90-day, 10,000 patient, Phase III, ACTIV-3 trial (NCT04501978) to determine whether adding the monoclonal antibody to remdesivir improved clinical status. NIH discontinued enrollment of patients in the BRII-196/BRII-198 arm of the trial when a futility analysis by the data and safety monitoring board did not find a benefit with the combination in an analysis of data from 343 patients.
The NIAID is evaluating the combination of BRII-196 and BRII-198 in the treatment of mild-to-moderate COVID-19 in patients who do not required hospitalization in the ACTIV-2 trial (NCT04518410).
The 15,000 patient RECOVERY trial (NCT04381936) has several arms testing lopinavir-ritonavir, dexamethasone, hydroxychloroquine, azithromycin, tocilizumab, convalescent plasma, immunoglobulin (IVIG), the monoclonal antibody combination REGN-COV2, aspirin, baricitinib, and colchicine. British researchers discontinued enrollment in the colchicine arm of the trial, when the independent Data Monitoring Committee did not find a reduction in 28-day mortality (20% colchicine vs 19% usual care alone).
NIH recommended adding tocilizumab to dexamethasone in hospitalized patients who are exhibiting rapid respiratory decompensation due to COVID-19, which includes patients within 24 hours of admission to the ICU that require invasive mechanical ventilation, noninvasive mechanical ventilation or high-flow nasal cannula oxygen, and non-ICU patients recently admitted to the hospital with a rapidly increasing need for oxygen that have significantly increased markers of inflammation. Some NIH Panel members would also recommend tocilizumab if patients exhibit rapidly increasing oxygen needs while receiving dexamethasone and have a C-reactive protein level of 75 mg/L or greater but who do not yet require noninvasive mechanical ventilation or high-flow nasal cannula oxygen.
On 2/27/2021 the FDA granted an emergency use authorization (EUA) to Johnson and Johnson’s COVID-19 vaccine for the prevention of COVID-19 for individuals 18 years of age and older. Vaccine Fact Sheets are available for Healthcare Providers and Vaccine Recipients/Caregivers. The CDC's Advisory Committee on Immunization Practices (ACIP) recommend the Johnson & Johnson Covid-19 vaccine on 2/28/2021. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22 to 0 to recommend an emergency use authorization (EUA) for J&J COVID-19 vaccineas prophylaxis for COVID-19 infections for patients 18 years and older.
An FDA review of Johnson & Johnson's single dose COVID-19 vaccine, found it to be safe and effective, based on data from the 39,321 patient ENSEMBLE study. FDA reviewers confirmed the 66% overall efficacy. The review found the vaccine to be efficacious for all age groups and ethnicities but noted a decrease in efficacy for patients 60 years and older with risk factors. The vaccine was 77% efficacious at two weeks in preventing severe and critical COVID-19 and 85% efficacious at four weeks. J&J’s vaccine was less effective against the South African variant (B.1.351) with efficacy of 52% at four weeks but maintained protection against severe and critical infection with 82% efficacy. In looking at only U.S. trial participants, efficacy was 72%. The most common adverse effects are injection site pain, headache, fatigue and myalgia. J&J's vaccine can be stored at refrigerator temperatures for at least 3 months.
A published retrospective review by Israeli researchers compared the outcomes of 596,618 patients that received the Pfizer-BioNTech COVID-19 vaccine to an equal number of non-vaccinated patients. Outcomes were assessed seven days and beyond after the second vaccination. The effectiveness of immunization was 92% in preventing documented infection, 94% to prevent symptomatic illness, 87% to prevent hospitalization, and 92% to prevent severe disease. the Pfizer-BioNTech vaccine was also found to be 90% effective in preventing asymptomatic infection.
The FDA approved a change to the storage and transportation requirements for the Pfizer-BioNTech COVID-19 Vaccine. The vaccine can now be transported and stored at conventional freezer temperatures for up to two weeks. There is no change to the requirements for thawed or diluted vials. Thawed vials, before dilution, can still be stored at refrigerator temperatures for up to 5 days. Diluted vials can be held at refrigerator temperature or room temperature for up to 6 hours.
Pfizer and BioNTech are evaluating the effects of a third vaccination (second booster vaccination), 6 to 12 months after the patients received the first of two doses in a Phase I trial. The goal of the study is to determine if boosting antibody titers will be enough to prevent infections from new COVID-19 variants. The companies are also discussing the design of a study to evaluate a variant-specific vaccine with the FDA and EU.
IDSA has updated their COVID-19 guidelines with a conditional recommendation to add tocilizumab to a corticosteroid in patients with severe or critical COVID-19 with elevated systemic inflammation.
In the 21-day, 803 patient, Phase IV, REMAP-COVID trial (NCT02735707), the number of organ support-free days were 10 for tocilizumab, 11 for sarilumab and none for standard of care in patients with critical COVID-19 receiving organ support in intensive care. In-hospital mortality was 27% with the pooled interleukin-6 receptor antagonist groups (tocilizumab and sarilumab), compared to 36% with 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.
In the 28-day, 452 patient, Phase III COVACTA trial (NCT04320615), treatment with tocilizumab improved the clinical status (7 point scale ranging from discharge or death) by a non-significant 1 point compared to placebo in hospitalized patients with severe COVID-19-associated pneumonia. There was no difference in mortality between tocilizumab and placebo, but patients treated with tocilizumab were discharged six days sooner, spent 5.8 less days in ICU and needed a ventilator for 5.5 fewer days.
NIH recommends the use of bamlanivimab 700 mg plus etesevimab 1,400 mg in combination for the treatment of outpatients with mild-to-moderate COVID-19 who are at high risk for clinical progression. The risk factors defined in EUA for bamlanivimab plus etesevimab BMI of 35 or more, diabetes, chronic kidney disease, or an immunocompromising condition; all adults 65 and older; adults 55 and older with cardiovascular disease, hypertension or respiratory disease, and those aged 12-17 years with sickle cell disease, neurodevelopmental disorders, respiratory disease, BMI in the 85th or greater percentile or congenital heart disease. The NIH recommends against use of bamlanivimab plus etesevimab in patients hospitalized for COVID-19 unless they are part of a clinical trial.
A meta-analysis of four published and six unpublished convalescent plasma trials involving 11,782 patients with COVID-19 did not find a reduction in mortality or a positive benefit on other clinical measures compared to placebo.
Stay informed, subscribe to the Prescribe Right Pharmaceutical Pipeline Tracker