COVID-19 Drug Research Roundup

COVID-19 Therapies:

Researchers at the University of California (UC) San Diego Health and Johns Hopkins University have launched randomized, double-blind clinical trials to study how well convalescent plasma therapy reduces symptoms of COVID-19 in outpatients. Additionally, the clinical trials will test the efficacy of convalescent plasma in preventing COVID-19 in patients exposed to the novel coronavirus. The investigators will administer one intravenous infusion of blood plasma containing high levels of COVID-19 antibodies from survivors or a placebo plasma without these antibodies. Participants will be monitored over a four-week period for either the onset or progression of COVID-19. The investigators will also look for evidence of long-term immunity at three months following infusion. The trials, which expect to recruit 1,100 participants, will be overseen by researchers from Johns Hopkins University and will be conducted at multiple trial sites across the U.S. The trial at UC San Diego Health launched in July 2020 and has so far enrolled 31 of the anticipated 151 participants.

Northwell Health’s research arm Feinstein Institutes has launched a fully virtual trial to study whether histamine-2 blocker famotidine is an effective treatment for COVID-19. The study is currently recruiting nonhospitalized patients with mild-to-moderate COVID-19 across New York City. Patients will receive either 240 mg famotidine or placebo each day for up to 14 days. Investigators will also administer training to participants on how to track data at home using a Bluetooth-enabled scale, thermometer, spirometer, pulse oximeter, fitness tracker and iPad.

Interim results from a multiplatform randomized trial shows that full-dose blood thinners improved outcomes for hospitalized patients with moderate COVID-19. The study, backed by the National Institutes of Health, included 1,000 patients with moderate COVID-19 who were hospitalized at more than 300 hospitals across the globe. Patients treated with full-dose heparin had a lower likelihood of requiring life support, including mechanical ventilation. The full-dose blood thinners were also considered safe and better than standard dosing. Researchers are currently studying whether the anticoagulant can also reduce mortality in these patients.

The first three ICU-admitted patients with COVID-19 in Sorrento Therapeutics’ ongoing phase 1b study were discharged from the hospital within a week after starting infusions of COVI-MSC, the company’s human allogeneic adipose-derived mesenchymal stem-cells treatment. Patients in the study were admitted to the ICU for COVID-19-induced acute respiratory distress or acute respiratory distress syndrome and received infusions of COVI-MSCs every other day for a total of three infusions. A fourth patient who had been hospitalized for more than two weeks improved rapidly after receiving three infusions of the therapy. Researchers found no evidence of infusion-related safety events in these patients.

Bristol Myers Squibb has been granted global rights to two anti-SARS-CoV-2 antibodies developed by the Rockefeller University. Under terms of the deal, Rockefeller will receive royalties on future sales of the product. The antibodies entered a 15-participant phase 1 study last month. The study’s primary objectives are to assess the intravenous and subcutaneous administration of various doses of the antibodies in healthy volunteers. The company says it plans to make the antibodies available for low- and middle-income countries, pending successful completion of a future registrational program.

A phase 1 trial of Selva Therapeutics’ COVID-19 treatment candidate SLV213 met its primary objective of showing safety and tolerability. The small molecule drug, developed through research from the University of California San Diego, blocks viral entry into cells. Preclinical research suggests the candidate exhibits broad antiviral activity against several coronaviruses as well as Ebola viruses and paramyxoviruses. The phase 1 trial from Selva showed no dose-limiting toxicities in any dose group, suggesting the therapy is safe. Selva says it plans to advance the candidate into a phase 2 study of nonhospitalized patients with COVID-19.

CalciMedica’s lead clinical compound, Auxora, led to decreased levels of a major clotting and inflammatory marker (D-dimer) in an open-label, placebo-controlled trial of patients with severe COVID-19 pneumonia. Patients in this 17-person trial received either Auxora with standard of care or standard of care alone. Those who received standard of care only developed femoral deep vein thrombosis, but no evidence of thromboembolic disease was found for patients treated with Auxora. The company plans to enroll up to 400 patients with severe COVID-19 in a blinded, placebo-controlled study to further evaluate the efficacy and safety of Auxora. This study will include the use of both remdesivir and dexamethasone for the standard-of-care regimen.

Matrix Medical Network and AstraZeneca have announced a collaborative agreement to accelerate a trial in the U.S. for AstraZeneca’s AZD7442, a long-acting monoclonal antibody (LAAB) combination and potential preventative therapy for COVID-19. The phase 3 STORM CHASER trial will be supported by Matrix using the company’s mobile health clinics. Matrix will meet trial volunteers at their home and work. The study will test the efficacy and safety of AZD7442 as a postexposure prophylactic in up to 1,125 volunteers in both the U.S. and the UK.

A randomized, double-blind, placebo-controlled study from Bangladesh’s International Center for Diarrheal Disease Research (ICDDR) has found that ivermectin reduced the duration of viral clearance in patients with early onset COVID-19 and mild COVID-19. The study included 72 hospitalized patients in Dhaka, the capital of Bangladesh. Patients were randomized to either receive 12 mg of ivermectin, 12 mg of ivermectin plus doxycycline or a placebo. Ivermectin was administered once daily for five days. The research team from ICDDR found that the duration of virological clearance was shorter in the ivermectin treatment arms compared with placebo. No adverse events were reported during the trial.

Phase 2 trials from Enlivex Therapeutics, an Israel-based immunotherapy company, suggest the company’s experimental Allocetra therapy may improve survival in patients with severe and critical COVID-19. A total of 16 patients with severe disease had survived 28 days after receiving the therapy in the phase 2 trial. Nine trial participants were in critical condition at the start of the study, and two of these participants were still on ventilators in intensive care at the trial’s end. The 14 patients who fully recovered were discharged by the end of the study and were reportedly healthy. After receiving the therapy, the average duration of hospitalization for discharged patients was 5.3 days. Two phase 2 trials from Enlivex Therapeutics show the therapy was associated with a zero percent mortality rate in 21 severe-to-critical patients. Most patients in these trials had obesity and hypertension, two pre-existing risk factors for severe disease. Enlivex hopes to submit its phase 2 trial data to regulators this month for emergency authorization.

COVID-19 Vaccines:

Johnson & Johnson has applied to the FDA for Emergency Use Authorization of its single-dose COVID-19 vaccine and plans to apply to European regulators for conditional marketing authorization in a few weeks. The vaccine, which can be stored and shipped at normal refrigeration temperatures, showed an overall efficacy rate of 66 percent in a global phase 3 study, including protection against the South African variant of the SARS-CoV-2 virus.

UK researchers are set to begin testing two separate combinations of COVID-19 vaccines to see if the use of two products in sequence will boost immune response. The first approach, a trial in older adults of a two-dose pairing of the Pfizer/BioNTech and the AstraZeneca (AZ)/Oxford University vaccines, should have data to report by June, according to the National Institute of Health Research. The second study will combine the AstraZeneca (AZ)/Oxford University vaccine with the Russian Gamaleya Research Institute’s Sputnik V vaccine in trials in Azerbaijan, the United Arab Emirates and other Middle Eastern nations. Trials also may take place in Argentina, Belarus, Russia and the Ukraine.

Two COVID-19 vaccines from Sinopharm and Chongqing Zhifei Biological Products elicited an immune response against the South African COVID-19 variant in a clinical trial, but at levels lower than against the original SARS-CoV-2 virus. The study examined sera from 12 trial participants who received the vaccine. Sinopharm’s inactivated vaccine received conditional authorization in China in early January, and the vaccine has also received authorization for emergency use in Bahrain and the United Arab Emirates. Sinopharm previously reported the vaccine’s efficacy rate as 79.3 percent, but the company has yet to release full data from its phase 3 interim analysis. This lack of data transparency has caused outside speculation regarding the veracity of the vaccine’s efficacy claims. Less is known about the COVID-19 vaccine from Chongqing Zhifei. This vaccine is currently under investigation in a phase 3 trial in Asia.

Valneva, a French specialty vaccine company, has started production on its inactivated, adjuvanted COVID-19 vaccine candidate VLA2001. The vaccine candidate is currently being tested in a fully enrolled phase 1/2 clinical trial. Currently, VLA2001 represents the only inactivated COVID-19 vaccine candidate in clinical trials in Europe. The fully enrolled trial includes 150 healthy adults 18 to 55 years of age. Initial reports of the study are expected in April 2021.

GlaxoSmithKline (GSK) and Clover Biopharmaceuticals are ending their COVID-19 vaccine collaboration focused on GSK’s pandemic adjuvant system combined with Clover’s trimeric SARS-CoV-2 spike (S-Trimer) protein-based vaccine candidate. The GSK-adjuvanted vaccine induced high neutralizing antibody levels in a phase 1 study. Clover is moving to test its vaccine adjuvanted with Dynavax’s CpG 1018 plus alum in a global phase 2/3 trial, which is expected in the first half of this year. Phase 1 testing found that Dynavax’s adjuvant with a hepatitis B vaccine induced neutralizing antibodies in adult participants. Clover says it expects to produce millions of doses of the vaccine this year and up to 1 billion doses per year.

An oral COVID-19 vaccine from Vaxart produced a T-cell responsible for eliminating virus-infected cells in approximately 75 percent of participants in an early-stage clinical trial of 35 healthy adults. The vaccine, dubbed VXA-CoV2-1, is a tablet that can be stored at room temperature. The vaccine was given to study participants 29 days apart in the two low-dose groups. Another group received either a single low or high dose of VXA-CoV2-1. The reported responses were higher than that observed with vaccines from Moderna and Pfizer. The neutralizing antibodies were not detected in volunteers after the single vaccine dose. No severe adverse events were reported in the study. The company is now planning to run a phase 2 study of the vaccine sometime this year.

AstraZeneca says data from its phase 3 study conducted in the UK, Brazil and South Africa suggest its COVID-19 vaccine, co-developed with the University of Oxford, may be more effective when given 12 weeks apart. According to the researchers of the study, the vaccine efficacy rate reached 82.4 percent in 1,293 patients who received two doses of the vaccine with the 12-week dosing interval. The company is unsure how these new data will affect the FDA’s decisions on authorizing the vaccine.

Updated phase 3 data suggest Gamaleya Institute’s two-dose COVID-19 vaccine Sputnik V is 92 percent effective against COVID-19. The data are based on an analysis of 78 confirmed COVID-19 cases. A total of 16 cases of COVID-19 out of 15,000 vaccinated participants were reported following the second dose of the vaccine, while 62 confirmed cases of COVID-19 were reported in 5,000 participants who received placebo. The updated findings are similar to results from an analysis by the Russian Direct Investment Fund, which indicated the Sputnik V had an efficacy rate of 92 percent.

COVAXX has begun enrollment for a phase 2 clinical trial of its multitope peptide-based COVID-19 vaccine candidate UB-612. The multicenter study, conducted at 11 medical centers and hospitals in Taiwan, will enroll up to 3,850 participants, including adolescents, adults and seniors. Researchers will explore the vaccine’s immunogenicity, safety and tolerability. COVAXX has also developed a partnership with the University of Nebraska Medical Center to perform clinical trials of its vaccine in the U.S. The company has also partnered with Diagnosticos da America to conduct phase 2/3 clinical trials in Brazil. Additionally, COVAXX has partnered with Indian pharmaceutical company Aurobindo Pharma to help with clinical testing, manufacturing and distribution of the vaccine in India.