COVID-19 Drug Research Roundup

COVID-19 Vaccines:

China has moved past its original plan of only providing Sinopharm’s COVID-19 vaccine candidate to high-risk individuals, such as healthcare workers, and has instead started administering the vaccine to all citizens under an Emergency Use Authorization (EUA). Phase 3 trials studying this candidate and several others are still in progress, however, raising questions regarding the safety and efficacy of the vaccines in the general population. The United Arab Emirates, which is working with China in a phase 3 trial of Sinopharm’s COVID-19 vaccine, has also granted an EUA to the candidate for frontline healthcare workers.

Pfizer’s COVID-19 vaccine, BNT162b2, produced mostly mild-to-moderate adverse reactions in patients who received the vaccine, according to findings from a 30,000-participant phase 3 trial. Interim safety results from this trial show that approximately 38 percent of patients who received one 30-mcg dose experienced fatigue, while another 35 percent experienced headache and 15 percent had chills. Fever, chills and joint pain were reported in 11 percent of patients. Adverse events were reported at a higher frequency among participants between the ages of 18 and 64 years compared with those 65 to 85 years of age. Those who received a second dose of the vaccine also experienced fatigue (36 percent), headache (28 percent) and muscle pain (18 percent), all of which were also reported at a higher frequency in the younger cohort. An independent data monitoring committee has yet to raise any concerns about the vaccine. Pfizer and its co-vaccine developer, BioNTech, has since submitted to the FDA a protocol for expanding trial enrollment to 44,000 participants. The request was made in an effort to include a broader population of patients and to enroll participants as young as 16 years of age as well as individuals with chronic illness, stable HIV, hepatitis C or hepatitis B infection.

Indian pharma company Dr. Reddy’s has agreed to assist in late-stage trials of Russia’s COVID-19 vaccine, Sputnik V. The Russian Direct Investment Fund (RDIF) has previously stated that it will supply up to 100 million doses of the vaccine to Dr. Reddy’s if the candidate receives regulatory approval in India.

AstraZeneca (AZ) and the University of Oxford are restarting their phase 3 COVID-19 vaccine trial in the UK, just under a week after the study was halted due to a serious safety concern. AstraZeneca has not disclosed information regarding this safety event. Up to 18,000 trial participants have already received the company’s AZD1222 vaccine as part of its phase 3 trial. The company’s U.S. trial is still on hold as the FDA looks into the safety issue. FDA Commissioner Stephen Hahn said the agency will engage in “very significant work” with AZ to determine what caused the serious adverse event.

The country of Brazil has authorized AstraZeneca to enroll an additional 5,000 volunteers in phase 3 trials of the company’s COVID-19 vaccine. This authorization was made in an effort to bolster safety and efficacy results for the vaccine. So far, approximately 4,600 participants in Brazil have received the vaccine candidate.

Moderna has set a bar for seeking emergency approval for its COVID-19 vaccine candidate, saying that it must prove to be at least 70 percent effective before it will file for an EUA. That threshold is higher than FDA’s 50 percent efficacy requirement. As of Sept. 16, the company’s phase 3 trial of its candidate, mRNA-1273, had enrolled 25,296 participants, and just over 10,000 participants have received their second doses.

A total of one out of seven volunteers who have received Russia’s controversial Sputnik V COVID-19 vaccine have reported vaccine-related side effects, including muscle pain and weakness. More than 300 of the planned 40,000 volunteers have received the vaccine so far, with 14 percent reporting complaints of weakness, muscle pain and occasional increases in body temperature.

Turkey has initiated phase 3 trials of an experimental COVID-19 vaccine from China-based Sinovac. Between 1,200 and 1,300 healthcare workers will receive the vaccine over 10 days, while a second dose will be administered two weeks later. The trial will then administer the vaccine in patients with chronic diseases. The current enrollment goal is set for 13,000 participants.

COVID-19 Therapies:

The National Institutes of Health (NIH), as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, has launched two of three adaptive phase 3 trials investigating the efficacy and safety of blood thinners for the treatment of COVID-19. The NIH trials, collectively referred to as ACTIV-4 Antithrombotics, will be conducted at more than 100 sites across the globe and will enroll hospitalized patients, those who have not been hospitalized and patients who had been discharged following hospitalization for moderate-to-severe COVID-19. All three trials will be funded through the U.S. government’s Operation Warp Speed initiative and will study the effects of varying doses of heparin and apixaban.

An investigational COVID-19 antibody cocktail from Regeneron Pharmaceuticals has been added to the UK’s phase 3 RECOVERY trial. The therapy, REGN-COV2, consists of two noncompeting, virus-neutralizing antibodies that bind to the critical receptor-binding domain of COVID-19’s spike protein. The late-stage trial will combine the antibody cocktail with standard of care, and the efficacy and safety of this approach will be compared with standard of care alone in up to 4,000 hospitalized patients with COVID-19. This will be the fourth phase 3 trial of REGN-COV2 to date. Currently, the drug is in late-stage testing in the U.S. as a prophylactic regimen for COVID-19 as well as for the treatment of patients with COVID-19 infection in phase 2/3 trials.

Treatment with a combination therapy comprising Eli Lilly’s rheumatoid arthritis drug baricitinib and Gilead Sciences’ remdesivir was associated with a reduction in time to recovery in hospitalized patients with COVID-19 when compared with remdesivir alone, according to findings from a recent late-stage trial. The trial — Adaptive COVID-19 Treatment Trial 2 (ACTT-2) — is being conducted at approximately 100 sites across the globe. Lilly plans to discuss the potential for an EUA of the combination therapy with the FDA, based on emerging data from the ACTT-2.

Galera Therapeutics has administered avasopasem manganese (GC4419) to its first patient in a phase 2 trial studying the therapy in critically ill patients with COVID-19. The study is examining the efficacy and safety of GC4419 compared with a placebo, specifically in regard to its ability to reduce 28-day mortality, in up to 50 hospitalized adult patients. Treatment consists of a 90-mg dose of GC4419 or a placebo administered via infusion twice daily for seven days

The FDA has approved an Investigational New Drug application to support a clinical trial of human-cord tissue mesenchymal stromal cells (hCT-MSC) for the treatment of multisystem inflammatory syndrome in children. The trial is being conducted on behalf of the Cura Foundation with the Marcus Foundation, Sanford Health and Alliance for Cell Therapy Now. A multisite pilot study will commence in late September 2020.

Rigel Pharmaceuticals has initiated a phase 2 trial studying oral spleen tyrosine kinase inhibitor fostamatinib for the treatment of hospitalized patients with COVID-19. The study, which is being conducted at the NIH Clinical Center in Bethesda, Md., will randomly assign hospitalized patients to either fostamatinib or a matching placebo, and outcomes will be assessed at 60 days. Currently, Imperial College London is conducting a phase 2 trial that is evaluating the efficacy of fostamatinib for managing COVID-19 pneumonia.

Eli Lilly’s neutralizing COVID-19 monoclonal antibody LY-CoV555 has reduced the risk of hospitalization by 72 percent compared with a placebo in a mid-stage trial of 452 patients with mild-to-moderate COVID-19. Around 1.7 percent of patients who received the drug in the trial were either hospitalized or admitted to the emergency room, while 6 percent of hospitalized patients received a placebo. The trial is ongoing and is evaluating LY-CoV555 and LY-CoV016, the company’s second antibody, as an outpatient treatment for COVID-19. Eli Lilly is also conducting another phase 2 study of the drug in patients with newly diagnosed COVID-19 as well as in a phase 3 trial for the prevention of COVID-19 in residents and staff of long-term care facilities.