COVID-19 Update #61 for 1/7/2020

COVID-19 Vaccines
 
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. 
 
COVID-19 Antibodies
 
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.
 
COVID-19 Antiviral
 
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.

• An article posted on an editorial server describes compassionate use of opaganib in Israel for the treatment of severe COVID-19 (NCT04435106) in five patients and compared the results to an investigator-selected matched case-control group of 18 patients. All opaganib-treated patients were discharged on room air and none required ventilation, while 33% of standard care patients required mechanical ventilation. All patients in both groups received hydroxychloroquine and most also received azithromycin.
• Redhill Biopharm announced that in a 40 patient, Phase IIa U.S. trial (NCT04414618), treatment with opaganib reduced the need for oxygen compared to placebo in hospitalized patients with severe COVID-19 pneumonia requiring supplemental oxygen. 
• Redhill is evaluating the effect of opaganib on the need for mechanical ventilation in a 270 patient, Phase II/III trial (NCT04467840) in Israel, Brazil, Mexico and Russia. An interim analysis is planned after 135 patients have been enrolled.