COVID-19 updates
|
COVID-19 Antivirals
An unpublished, unreviewed report from the WHO sponsored, 11,266 patient, Phase II/III SOLIDARITY trial, did not find an improvement in hospitalized COVID-19 patients treated with remdesivir, hydroxychloroquine, lopinavir or interferon compared to no drug in mortality, initiation of ventilation or duration of hospital stay. A physician reviewer speculated that remdesivir may be more effective when given early in the infection to patients at high risk for progression. Leronlimab is a monoclonal antibody that blocks the CCR5 chemokine receptor, which results in an inhibition of a virus’ ability to enter leukocytes. Leronlimab was originally developed by CytoDyn as a treatment for HIV-1 infection.
NIH will evaluate the effect of three anti-inflammatories on suppressing cytokine storm in COVID-19 patients in the 2,100 Patient, Phase III ACTIV-1 IM trial. The drugs that will be used in ACTIV-1 IM include TNF blocker, infliximab (Remicade, J&J); the CTLA-4 immunoglobulin, abatacept (Orencia, BMS); and the investigational CCR2/CCR5 agonist cenicriviroc (AbbVie). In a 126 patient, Phase II, Italian trial (NCT04346355), treatment with tocilizumab did not reduce intensive care admission with invasive mechanical ventilation, death from all causes, or clinical aggravation compared to placebo in patients with early-stage COVID-19 pneumonia. In a 131 patient, Phase II, French trial (NCT04331808), treatment with tocilizumab did not improve clinical progression at day 4, but did reduce death or the need for high-flow oxygen or ventilation at day 14 (24% vs. 36%) compared to placebo in patients with moderate-to-severe COVID-19 pneumonia. A 3,924 patient retrospective U.S. analysis found a lower risk for death in 433 patients that received tocilizumab compared with those not treated with tocilizumab in critically ill COVID-19 patients. In a 243 patient, Phase III, U.S. trial (NCT04356937), treatment with tocilizumab did not reduce intubation or death compared to placebo in patients with severe COVID-19. COVID-19 Monoclonal Antibodies
BARDA has provided a $486 million Project Warp Speed grant to AstraZeneca to evaluate the long-acting monoclonal antibody combination, AZD7442, in two Phase III trials. A 5,000 patient trial will evaluate AZD7442 to prevent COVID-19 for up to 12 months and a 1,100 patient trial will evaluate the antibody as post-exposure prophylaxis. AstraZeneca will supply up to 100,000 doses by the end of 2020 and the US can acquire an additional one million doses in 2021 under a separate agreement. NIAID is comparing bamlanivimab plus remdesivir to remdesivir alone in the treatment of hospitalized patients with COVID-19 in the 10,000 patient, Phase III, ACTIV-3 trial (NCT04501978). The trial was initiated in August 2020, but temporarily paused in October 2020 on the recommendation of a data and safety monitoring board to allow time to review safety data. The FDA issued a violation notice to Lilly due to quality review issues, which would need to be fixed, to be in compliance with manufacturing standards for authorization of a drug. COVID-19 Vaccines Vaxart is developing the non-replicating adenovirus type-5 (Ad5) viral vector DNA virus, VXA-CoV2-1.
In a 195 patient, Phase I trial (NCT04368728), two vaccine candidates (BNT162b1 and BNT162b2) were tested in healthy adults. Patients that received BNT162b2 had a lower incidence and severity of systemic reactions than BNT162b1. No safety issues were identified, but most participants reported mild to moderate injection site pain. Tiredness, headaches and fever was reported after the second dose. Both vaccines elicited antibody levels one-month after a second dose of vaccine that were greater than levels seen in a group of recovered COVID-19 patients. COVID-19 Treatments Risankizumab (Skyrizi, Boehringer Ingelheim and AbbVie) is a monoclonal antibody approved for the treatment of severe plaque psoriasis.
The NIH provides guidelines for the treatment of patients with COVID-19 that are continuously updated. A list of updates and recommendations by date of publication are provided to help health care practitioners stay current. The guidelines include an Overview of Therapeutic Management of Patients with COVID-19, based on disease severity. There is also a review of evidence that supports or refutes the use of therapies and a recommendation by NIH for or against use of the therapies. Current treatment recommendations are organized by severity of disease in an easy-to-use graphic.
COVID-19 Monoclonal Antibodies
Lilly announced interim data from 268 patients enrolled in the 800 patient, Phase II, BLAZE-1 trial (NCT04427501), where treatment with the combination of bamlanivimab and etesevimab reduced viral load at day 11. Use of bamlanivimab plus etesevimab resulted in 0.9% of patients requiring hospitalization or an ER visit compared to 5.2% in the placebo group. Lilly submitted a request for an emergency use authorization (EUA) for its monoclonal antibody bamlanivimab in October and plans to request an EUA for the combination of the two monoclonal antibodies, bamlanivimab and etesevimab, in November 2020. Regeneron submitted a request for an emergency use authorization for its monoclonal antibody combination, REGN-COV2. If granted, initial doses would be made available at no charge, because they are covered by a Warp Speed grant from BARDA. Hyperimmune Immunoglobulin NIAID is comparing a single dose of Anti-Coronavirus Immunoglobulin plus up to 10 days of remdesivir to remdesivir alone in the treatment of COVID-19 in the 28-day, 500 patient, Phase III ITAC trial (NCT04546581) in hospitalized patients with severe COVID-19. Baricitinib Lilly announced additional details from the Phase III, ACTT 2 trial (NCT04401579) where the largest benefit of adding baricitinib to remdesivir was seen in patients requiring supplemental oxygen or high-flow oxygen/non-invasive ventilation. Remdesivir The ACTT-1 investigators provided a final report on the NIAID sponsored study. In the 29-day, 1,062 patient, Phase III, Adaptive COVID-19 Treatment Trial (ACTT-1) (NCT04280705), patients treated with remdesivir for up to ten days had a median time of recovery (hospital discharge or returning to normal activity level) of 10 days compared to 15 days with placebo in patients with severe COVID-19. However, there was not a significant improvement for patients that required a ventilator or ECMO at study entry. At day 15, there was a significant difference in mortality with remdesivir compared to placebo (6.7% vs 11.9%), but the difference was no longer significant at 29 days (11.4% and 15.2%). Hydroxychloroquine 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. In the hydroxychloroquine arm of the RECOVERY trial, 1,561 patients that received hydroxychloroquine were compared to 3,155 that received usual care. There was no improvement in mortality at 28-days with hydroxychloroquine compared to usual care (27% vs 25%). Due to the lack of benefit seen at an interim analysis, the researchers discontinued enrollment in the hydroxychloroquine arm of the trial. COVID-19 Vaccines
The EMA has started a rolling review of AstraZeneca’s COVID-19 vaccine with early non-clinical data, while the FDA still has a hold in place for the U.S. Phase III trial. The EMA has also started a rolling review of BioNTech’s and Pfizer’s COVID-19 vaccine with early non-clinical data, a few days after initiating the rolling review for AstraZeneca’s vaccine. The National Academies of Sciences, Engineering, and Medicine have made recommendations to NIH regarding the distribution of a COVID-19 vaccine (s), when one or more are available.
VIR and GSK announced the initiation of the 1,300 patient, Phase III portion of the COMET-ICE trial to evaluate whether VIR-7831 prevents mild or moderate COVID-19 patients from worsening as indicated by an increase in hospitalizations or death. CPI-006 CPI-006 is a monoclonal antibody for CD73 that activates lymphocytes, induces the production of antigen-specific immunoglobulin from B cells and increases production of CD4+ and CD8+ cells. CPI-006 is being developed by Corvus Pharmaceuticals as a cancer treatment.
The 11,000 patient RECOVERY trial has several arms testing lopinavir-ritonavir, dexamethasone, hydroxychloroquine, azithromycin, tocilizumab, REGN-COV2 and convalescent plasma. In the lopinavir-ritonavir arm of the RECOVERY trial (NCT04381936), 1,616 patients that received lopinavir-ritonavir were compared to 3,424 patients that received only usual care. Lopinavir-ritonavir did not improve mortality at 28-days compared to usual care (23% vs 22%), nor did the drugs decrease the duration of hospital stay, or the risk of progressing to invasive mechanical ventilation. COVID-19 Vaccines
J&J initiated the 60,000 patient, Phase III, ENSEMBLE trial (NCT04505722) to evaluate a single dose of JNJ-78436735 for the prevention of COVID-19 in Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa and the United States. In an unreviewed trial report, JNJ-78436735 elicited neutralizing antibodies in a 394 patient, Phase I/II trial. The most frequent adverse events were injection site pain, fatigue, headache and myalgia. Novavax initiated a 10,000 patient, Phase III trial to evaluate two doses of NVX-CoV2373 given 21-days apart for the prevention of COVID-19 in the United Kingdom. At least 25% of trial participants will be 65 or older. The FDA placed a hold on a Phase II/III trial evaluating Inovio’s COVID-19 vaccine, INO-4800, due to questions regarding the vaccine and the Cellectra 2000 delivery device used in the trial. In a 40 patient, Phase I, NIAID-sponsored, open-label trial (NCT04283461), the antibody titers increased in patients > 56 that were similar to those seen in younger patients. Antibody titers further increased with a booster dose at 1-month. As with the trial of younger patients, serum-neutralizing activity was similar to the levels seen in recovered patients. Adverse events were primarily mild to moderate (e.g., chills, fatigue) and occurred more frequently after the second vaccination. COVID-19 Antibodies Regeneron announced data from the first 275 patients enrolled in a 1,300 patient, adaptative Phase I/II/III trial (NCT04425629), where treatment with REGN-COV2 lowered viral levels to a greater extent at increasing viral loads. The monoclonal antibody appeared to be more efficacious in patients that had not produced antibodies and/or had higher viral loads. REGN-COV2 may alleviate symptoms in a shorter time compared to placebo, but in the preliminary data, the numerical reduction (seronegative patients only) was not statistically significant. Favipiravir Toyama announced that 156 patient, Phase III trial, patients treated with favipiravir cleared SARS-CoV 2 viral RNA in 11.9 days compared to 14.7 days with placebo in Japanese patients with COVID-19 and non-severe pneumonia. COVID-19 Antibodies
Lilly announced interim data from the 800 patient, Phase II, BLAZE-1 trial (NCT04427501), where treatment with LY-CoV555 reduced viral load at day 11 with 2,800 mg, but not 700 mg or 7,000 mg compared to placebo in patients with mild to moderate COVID-19. A pooled analysis of all doses of LY-CoV555 found that 1.7% required hospitalization or an ER visit compared to 6% in the placebo group. COVID-19 Vaccines Merck initiated a 260 patient, Phase I/II trial (NCT04498247) to evaluate the safety, tolerability and immunogenicity of its COVID-19 vaccine, V591, in September 2020. CanSino is evaluating a two-dose regimen of Ad5-nCoV in a 168 patient, Phase I trial (NCT04552366) in China. COVID-19 Anti-Inflammatories Roche announced that in the 28-day, 389 patient, Phase III EMPACTA trial (NCT04372186), 12.2% of patients treated with tocilizumab progressed to mechanical ventilation or death compared to 19.3% of patients treated with placebo in hospitalized patients with COVID-19 who did not require noninvasive or invasive mechanical ventilation. Almost 85% of patients were non-white with the majority being Hispanic, with inclusion of Native American and Black populations. COVID-19 Vaccines
Gamaleya Research Institute is developing Gam-COVID-Vac (Sputnik V), a non-replicating adenovirus type-5 (Ad5) viral vector DNA virus. Russia approved the COVID-19 vaccine after limited Phase I testing.
Pfizer and BioNTech are evaluating BNT162b2 in a Pfizer funded, 44,000 patient, Phase II/III trial (NCT04368728) BNT162b2 will be administered as two 30 mcg immunizations given 21-days apart. The trial was expanded from its original 30,000 patients, in September 2020, to allow the vaccine to be tested in a larger more diverse population, including adolescents as young as 16 years of age and people with HIV, Hepatitis C, and Hepatitis B. Novavax purchased Praha Vaccines and its Czech Republic vaccine factory. That plant has an annual capacity of one billion doses per year. Novavax signed an agreement with Fujifilm Diosynth Biotechnologies to manufacture its COVID-19 vaccine, NVX-CoV2373, in North Carolina and Texas. Novavax also signed contracts with AGC Biologics and PolyPeptide to help produce its Matrix-M adjuvant. In addition Novavax has an agreement with Serum Institute of India to manufacture the antigen component of NVX‑CoV2373. The company now has six antigen production sites and three adjuvant manufacturing sites. This gives Novavax the capacity to produce two billion doses of the NVX-CoV2373 annually beginning in 2021. COVID-19 Treatment Granulocyte colony-stimulating factor (G-CSF) was evaluated as a treatment for COVID-19 in a Chinese trial. G-CSF increases peripheral blood leukocyte and lymphocyte and was theorized to be beneficial in COVID-19 patients with lymphopenia. Filgrastim (Neupogen, Amgen) is a G-CSF. Lenograstim is a G-CSF developed by Chugai and available in some countries as Granocyte.
Lilly announced that in the 29-day, 1,034 patient, Phase III, ACTT 2 trial (NCT04401579), baricitinib added to remdesivir reduced the time to hospital discharge by one day compared to remdesivir alone in hospitalized patients with COVID-19. ACTT 2 is sponsored by NIAID. COVID-19 Antibodies The University of Oxford will evaluate the effect of REGN-COV2 added to standard-of-care on all-cause mortality at 28 days in a new 2,000 patient arm of the RECOVERY trial. The 11,500 patient RECOVERY trial (NCT04381936) has several arms testing lopinavir-ritonavir, dexamethasone, hydroxychloroquine, azithromycin, tocilizumab and convalescent plasma. COVID-19 Vaccines
Gamaleya Research Institute is developing Gam-COVID-Vac (Sputnik V), a non-replicating adenovirus type-5 (Ad5) viral vector DNA virus. Russia approved the COVID-19 vaccine after limited Phase I testing.
AstraZeneca paused all clinical trials for its COVID-19 vaccine (AZD1222), on 9/6/2020, due an adverse event in one patient. The patient suffered neurological symptoms consistent with transverse myelitis. The UK Medicines Health Regulatory Authority investigated the occurrence as a potential safety problem and allowed the trial to continue on 9/12/2020. The FDA is still investigating the adverse event and had not allowed the trial to resume in the U.S. as of 9/15/2020. Pfizer and BioNTech are evaluating BNT162b2 in a Pfizer funded, 44,000 patient, Phase II/III trial (NCT04368728) BNT162b2 will be administered as two 30 mcg immunizations given 21-days apart. The trial was expanded from its original 30,000 patients, in September 2020, to allow the vaccine to be tested in a larger more diverse population, including adolescents as young as 16 years of age and people with HIV, Hepatitis C, and Hepatitis B. Novavax purchased Praha Vaccines and its Czech Republic vaccine factory. That plant has an annual capacity of one billion doses per year. Novavax signed an agreement with Fujifilm Diosynth Biotechnologies to manufacture its COVID-19 vaccine, NVX-CoV2373, in North Carolina and Texas. Novavax also signed contracts with AGC Biologics and PolyPeptide to help produce its Matrix-M adjuvant. In addition Novavax has an agreement with Serum Institute of India to manufacture the antigen component of NVX‑CoV2373. The company now has six antigen production sites and three adjuvant manufacturing sites. This gives Novavax the capacity to produce two billion doses of the NVX-CoV2373 annually beginning in 2021. COVID-19 Treatment Granulocyte colony-stimulating factor (G-CSF) was evaluated as a treatment for COVID-19 in a Chinese trial. G-CSF increases peripheral blood leukocyte and lymphocyte and was theorized to be beneficial in COVID-19 patients with lymphopenia. Filgrastim (Neupogen, Amgen) is a G-CSF. Lenograstim is a G-CSF developed by Chugai and available in some countries as Granocyte.
COVID-19 Anti-Inflammatories Lilly announced that in the 29-day, 1,034 patient, Phase III, ACTT 2 trial (NCT04401579), baricitinib added to remdesivir reduced the time to hospital discharge by one day compared to remdesivir alone in hospitalized patients with COVID-19. ACTT 2 is sponsored by NIAID. COVID-19 Antibodies The University of Oxford will evaluate the effect of REGN-COV2 added to standard-of-care on all-cause mortality at 28 days in a new 2,000 patient arm of the RECOVERY trial. The 11,500 patient RECOVERY trial (NCT04381936) has several arms testing lopinavir-ritonavir, dexamethasone, hydroxychloroquine, azithromycin, tocilizumab and convalescent plasma. Remdesivir
The FDA expanded the emergency use authorization for remdesivir to include treatment of any hospitalized adult or pediatric patients with suspected or laboratory-confirmed COVID-19, irrespective of their severity of disease. The expansion was based on evidence demonstrating a benefit in patients with mild-to-moderate disease. COVID-19 Antibodies AstraZeneca initiated a 48 patient, Phase I trial in August, to evaluate its two monoclonal antibody combination, AZD7442, as a treatment for hospitalized COVID-19 patients (NCT04507256). The trial is being sponsored by DARPA and BARDA. Vir and GSK initiated the Phase II/III, COMET-ICE trial in August to evaluate VIR-7831 as a treatment for COVID-19. The Phase II part of the trial will evaluate the safety and tolerability of VIR-7831 in 20 non-hospitalized, COVID-19 patients. The 29-day, 1,300 patient, Phase III part of the trial will evaluate whether VIR-783 prevents mild or moderate COVID-19 patients from worsening as indicated by an increase in hospitalizations or death. COVID-19 Vaccines The FDA’s Vaccine Advisory Committee will meet on October 22 for a general discussion on the development, authorization and/or licensure of vaccines to prevent COVID-19. No specific vaccine will be discussed at the meeting. The FDA plans to offer a free live broadcast of the meeting and make background material and slides available before the meeting. CanSino has canceled a Phase II/III trial in Canada, after the Chinese government refused to allow the company to ship the vaccine to Canada for the trial. The CanSino COVID-19 vaccine, Ad5-nCoV, is based on technology developed by Canadian firm NRC. Remdesivir
In an 11-day, 584 patient, Phase III, open-label trial (NCT04292730), patients treated with a 5-day course of remdesivir were more likely to have at least a 2-point improvement on a seven-point scale that runs from death to not hospitalized compared to placebo (70% vs 61%) in hospitalized patients with moderate COVID-19. A 10-day course of remdesivir did not differ from placebo (65% vs 61%), although most patients did not receive a full 10-days of treatment. Patients in the standard of care group were more likely to receive lopinavir-ritonavir, corticosteroids, hydroxychloroquine/chloroquine, azithromycin or tocilizumab. COVID-19 Antibodies 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 EUA was granted for any convalescent plasma product “collected by FDA registered blood establishments from individuals whose plasma contains anti-SARS-CoV-2 antibodies, and who meet all donor eligibility requirements." Fact sheets have been created for health care providers and patients. 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. In an unpublished, 35,322 patient, open-label trial, the seven-day mortality was 8.7% in patients treated with convalescent plasma within 3 days of diagnosis, and 11.9% if transfused four or more days later in patients hospitalized with COVID-19. Lower mortality was also seen with convalescent plasma that had higher antibody levels. Data from the trial was collected from patients treated through a convalescent plasma expanded access program for COVID-19 (NCT04338360). |
Stay informed, subscribe to the Prescribe Right Pharmaceutical Pipeline Tracker
Archives
October 2020
Categories |
RSS Feed