COVID-19 Drug Research Roundup
GlaxoSmithKline and Vir Biotechnology have filed for Emergency Use Authorization for their SARS-CoV-2 monoclonal antibody ahead of schedule, having recently stopped their phase 3 trial after seeing significantly positive results. The pair hope to receive emergency authorization for VIR-7831, a dual-action monoclonal antibody, for treating mild-to-moderate COVID-19 in patients age 12 years and up who are at risk of progressing to hospitalization or death. The companies have also filed a biologics license application for the coronavirus treatment candidate and are continuing submission talks with the European Medicines Agency and other regulators.
Incyte’s chemotherapy drug Jakafi failed to show benefit as a treatment for severe COVID-19 in a phase 3 trial. Although the study did not meet its primary endpoint, the company and its partner Novartis say they still plan to offer the therapy on a compassionate-use basis, as long as the FDA gives its approval. The rationale for making Jakafi available as a compassionate-use drug is based on the finding that it seemed to improve mortality rates among patients with severe COVID-19. While treatment with Jakafi in the phase 3 trial was associated with a mortality improvement that did not reach statistical significance overall, survival improvements did reach significance in a group of U.S. patients. These patients comprised more than 90 percent of the overall study cohort.
Anti-SARS-CoV-2 drug candidate DC402234, developed by Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, has entered into a phase 1 trial in the U.S. The drug is a peptidomimetic compound that was synthesized through the analysis of the crystal structure of the coronaviruses Mpro. In the new study, investigators hope to see that DC402234 can have significant activity against COVID-19. Researchers have previously found that DC402234 has effective inhibitory activity against the novel coronavirus that causes COVID-19. Clinical in vivo work also shows the compound has an overall good pharmacokinetic and safety profile.
Veyonda has been approved to advance to the final stage of the NOXCOVID-1 clinical trial, which will study Noxopharm’s first-in-class sphingosine-1-phosphate inhibitor in patients with moderate COVID-19. The first part of the NOXCOVID-1 trial included 26 patients with moderate COVID-19 who received escalating doses of the study drug. The 1,800-milligram dose in this study was generally well-tolerated and became the preferred dose for future trials. The second phase of the trial is recruiting between 10 and 15 patients with COVID-19 and moderate-to-severe lung dysfunction. Treatment will be administered for up to 14 days at the 1,800-milligram dose.
The European Medicines Agency (EMA) is recommending against the use of ivermectin for COVID-19 prevention outside the confines of a clinical trial. This recommendation was made after the EMA reviewed the latest evidence on ivermectin for COVID-19 prevention and treatment and concluded that the current data do not support the use of the drug in clinical practice. Similar sentiments have also been expressed by the FDA. In contrast, the National Institutes of Health (NIH) conducted a thorough and comprehensive review of ivermectin studies and meta-analyses and subsequently changed their recommendation on ivermectin from one of opposition to neutral in terms of its use in clinical practice.
A phase 2 clinical trial launched by BioAge Labs seeks to evaluate BGE-175, an oral inhibitor of prostaglandin D2 (PGD2) DP1 signaling, for the treatment of COVID-19 in patients 60 years of age and older. Prior phase 1 through phase 3 clinical trials on allergic rhinitis show BGE-175 was safe and generally well-tolerated in more than 2,400 people. The new phase 2 trial will enroll older hospitalized patients with COVID-19 who do not show signs of respiratory failure. A total of 132 patients from the U.S., Argentina and Brazil will be given daily doses of either BGE-175 or placebo for up to two weeks. Researchers will compare the groups in terms of the proportion of patients who die or develop respiratory failure within 28 days. The study will also examine rates of viral load, clinical improvement or worsening, the incidence and duration of supplemental ventilation or oxygen, as well as time to discharge or rehospitalization.
AstraZeneca’s investigational long-acting antibody combination AZD7442 has been added to the NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) master protocol. The sub-study will evaluate the safety and efficacy of AZD7442 for the treatment of COVID-19 in hospitalized patients with mild-to-moderate infection. Participants will be randomly assigned to either saline placebo, AZD7442 or other experimental antibodies. Once 150 patients are enrolled and the antibody demonstrates safety and efficacy, researchers will expand the cohort to up to 700 patients. Patients with more severe COVID-19 may be included in ACTIV during the expansion.
The HEAL-COVID clinical trial is being launched in the UK to identify therapies that could be used to manage the after-effects of COVID-19. Participants will be randomly assigned to apixaban or atorvastatin to see if either therapy can reduce the number of patient readmissions caused by COVID-19-related complications. Researchers of the trial hope to add a third drug to the trial in the next few weeks. The study is headed by researchers from the Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge.
An early phase, open-label study shows Kaleido Biosciences’ KB109, a microbiome metabolic therapeutic, reduced COVID-19-related healthcare utilization by 51 percent. Healthcare utilization, as defined in this trial, included hospitalizations as well as visits to the emergency room and urgent care. Additionally, treatment with the drug candidate shortened the symptom duration in patients with mild-to-moderate COVID-19. The study included 350 patients with mild-to-moderate disease, all of whom used self-supportive care to manage their condition. Half of the cohort received KB109 at home. Those with one or more comorbidities who received KB109 also had a shortened median time to resolution of symptoms from 30 days to 21 days. More side effects were observed with KB109, including gastrointestinal-related adverse events (21 percent vs. 5 percent in the self-supportive care alone arm).
Pfizer has launched a phase 1 trial in the U.S. of PF-07321332, an oral COVID-19 antiviral and protease inhibitor designed to stop viral replication. Compared with an intravenous infusion, the oral drug design could be better accepted by patients. Previous in vitro research shows PF-07321332 has strong antiviral activity against the novel coronavirus, in addition to other coronaviruses. Researchers involved in the phase 1 trial will assess the investigational agent’s safety, tolerability and pharmacokinetics at several different doses. Only 60 participants will be enrolled. Concurrently, Pfizer is studying PF-07304814, an intravenously administered protease inhibitor, in a phase 1b study of hospitalized patients with COVID-19. This study plans to enroll up to 72 patients.
Antibody cocktail REGEN-COV (casirivimab/imdevimab), from Regeneron Pharmaceuticals and Roche, was shown to reduce the risk of hospitalization or death by up to 70 percent in high-risk, nonhospitalized patients with COVID-19 in a phase 3 trial. In this 4,567-person study, treatment with REGEN-COV was associated with a reduction in the duration of symptoms from two weeks to 10 days. The company plans to submit the new late-stage trial results to the FDA to support a Biologics License Application. The antibody cocktail has also been studied in other trials, including the UK’s phase 3 RECOVERY trial. Back in November, the FDA granted REGEN-COV an Emergency Use Authorization (EUA) for the treatment of mild-to-moderate COVID-19 in patients at high risk of progression to severe disease or hospitalization.
Novavax is getting ready to submit EUA applications for its COVID-19 vaccine in the U.S. and for conditional authorizations in the UK and the EU. The company says it will file first with the UK’s Medicines and Healthcare products Regulatory Agency sometime in the second quarter.
There is a clearer timeframe for an FDA EUA filing, with the company’s CEO, Stanley Erck, pledging at the beginning of March that the vaccine could receive FDA authorization by May. However, that projection could be pushed back if the agency wants to see U.S. trial data for the vaccine. Erck said that Novavax hopes to support its EUA filing with data from its late-stage UK trial, which found the inoculation demonstrated 89.3 percent efficacy.
Pfizer and BioNTech have begun a clinical trial of their COVID-19 vaccine in children six months to 11 years old, with phase 1 expected to enroll 144 participants. The study will initially seek to identify the preferred dose level (10, 20 or 30 micrograms) in three age groups — five to 11 years, two to five years and six months to two years. Once the dose level is confirmed, the phase 2/3 portion of the study will enroll up to 4,500 participants who will receive either the vaccine or a placebo.
AstraZeneca announced its vaccine AZD1222 was 76 percent effective against symptomatic COVID-19 in a phase 3 trial in the U.S. The overall study cohort included 32,449 participants across 88 trial centers in the U.S., Chile and Peru. Patients were given two doses of AZD1222 four weeks apart. The primary efficacy analysis comprised 190 symptomatic COVID-19 cases. In addition to the main efficacy finding, the AstraZeneca vaccine, developed by researchers at the University of Oxford, was also 100 percent effective against severe or critical disease and hospitalization. The COVID-19 vaccine candidate also demonstrated an 85 percent efficacy against symptomatic COVID-19 in patients age 65 years and older. Based on these findings, AstraZeneca says it plans to file an EUA application for AZD1222 in the U.S. in the first two weeks of April.
CureVac has expanded its phase 2b/3 clinical trial protocol in Europe and Latin America to see if its vaccine is effective against different strains of the novel coronavirus. Investigators have also modified a phase 2a clinical trial protocol in Peru and Panama, a change that now includes in the trial an additional secondary endpoint for vaccine efficacy. CureVac expects data from both studies to be available during the second quarter of this year and hopes to file its vaccine for authorization in Europe at the same time. Phase 1 data released last November show two doses of CureVac’s vaccine candidate was associated with seroconversion of virus neutralizing antibodies in 251 patients.
Oramed Pharmaceuticals and Premas Biotech have launched a joint venture company called Oravax Medical, which will be focused on the development of the world’s first oral COVID-19 vaccine. The new company will harness Oramed’s oral delivery mechanism and Premas’ vaccine technology to develop a vaccine candidate that will target three structural proteins on SARS-CoV-2. The design of this candidate, according to the company, should make the vaccine easier to modify for new variants of the novel coronavirus. Additionally, the oral delivery of the vaccine makes it easier to administer and distribute. A pilot study previously showed the oral vaccine supported systemic immunity. The company plans to launch a phase 1 study on the candidate in the second quarter of 2020.
A recent study from Israel shows the Pfizer/BioNTech COVID-19 vaccine is not as effective against the South African SARS-CoV-2 strain compared with the coronavirus strain first identified in the UK. The study was an analysis of blood samples from 10 patients who had recovered from COVID-19. Researchers collected samples at 21 days after the first vaccine dose and nine to 11 days following the second vaccine dose. The study found the vaccine generated high antibody levels against the UK variant but only moderate neutralization was observed against the variant from South Africa. In contrast, another study reported earlier this month showed the Pfizer/BioNTech vaccine was 94 percent effective against asymptomatic COVID-19 infections.
Preliminary results from Sinovac Biotech’s phase 1 and 2 clinical trials show its COVID-19 vaccine CoronaVac was safe and generated immune responses in children and adolescents. These preliminary data were from studies that included more than 500 patients between three and 17 years of age who received two shots of either the vaccine or a placebo. In terms of safety, most adverse reactions observed in the patients were mild in severity. Two children who received a low vaccine dose had high fever following inoculation. Antibodies generated after vaccination with CoronaVac were higher than previously observed in adults and elderly patients. A lower vaccine dose worked better in children between the ages of three and 11 years, and a median dose worked best for those between age 12 and 17.
The first patients have been dosed in Clover Biopharmaceuticals’ and Dynavax Technologies’ global phase 2/3 trial of Clover’s protein-based S-Trimer COVID-19 vaccine candidate adjuvanted with Dynavax’s CpG 1018 plus alum. The randomized controlled trial will evaluate the safety, efficacy and immunogenicity of the two-dose vaccine. More than 22,000 adults and elderly participants will be enrolled at sites across Latin America, Asia, Africa and Europe. Clover will conduct an interim analysis to determine if the vaccine offers favorable effects in this study population. Current enrollment rates and COVID-19 cases in the study suggest an interim analysis of the primary endpoint should occur sometime in the middle of this year.