COVID-19 Drug Research Roundup

COVID-19 Therapies:

Merck has decided to end research and development on MK-7110, an experimental oral drug for treatment of hospitalized coronavirus patients that had shown promise in a late-stage trial. The company also announced last week that, along with its partner Ridgeback Biotherapeutics, it will not advance to a phase 3 trial of hospitalized COVID-19 patients for their oral antiviral molnupiravir but will go ahead with a late-stage trial that evaluates it as a treatment for nonhospitalized patients.

A phase 3 study shows treatment with REGEN-COV, Regeneron Pharmaceuticals’ COVID-19 antibody cocktail containing casirivimab and imdevimab, reduced symptomatic infections by 81 percent. The study, conducted with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), included more than 1,500 people living in a household with someone positive for COVID-19. Study participants received either placebo or a subcutaneous injection of 1,200 mg of REGEN-COV. People infected with SARS-CoV-2 generally experienced resolution of their symptoms within one week following treatment with the antibody cocktail. In contrast, those treated with placebo who developed a symptomatic infection experienced symptom resolution within three weeks. A separate late-stage study from the NIAID also found that REGEN-COV reduced the risk of progression to symptomatic COVID-19 by up to 31 percent over 29 days. This separate trial included 204 asymptomatic COVID-19 patients. Those who progressed to symptomatic infection but were treated with REGEN-COV had a 45 percent reduction in the number of weeks spent with symptoms. Additionally, the viral burden of those treated with REGEN-COV was reduced by more than 90 percent.

Treatment with a heart failure and diabetes drug from AstraZeneca did not lead to a reduction in the risk of organ dysfunction and death in high-risk, hospitalized patients with COVID-19 in a recent phase 3 study. The study was launched in April 2020 and examined the efficacy and safety of the sodium-glucose co-transporter-2 inhibitor, marketed as Farxiga (dapagliflozin), in patients with COVID-19 at risk of developing serious complications. Researchers enrolled 1,250 volunteers, all of whom received treatment for 30 days. The investigators assessed whether the therapy could help manage heart, kidney or metabolic comorbidities often exacerbated by COVID-19. Full trial results will be released by AstraZeneca in the next month.

Gilead Sciences has said it ended a late-stage study examining the efficacy and safety of intravenous Veklury (remdesivir) in nonhospitalized patients with COVID-19 who were at high risk of disease progression. According to Gilead, the trial was halted because the company does not see how a multiple-day infusion therapy, such as the intravenous remdesivir formulation, can address an unmet need in nonhospitalized patients who receive the treatment in a healthcare setting. Gilead says there were no safety or efficacy concerns that led to stopping the study. While the study has been stopped, researchers will continue to monitor trial participants who have received the investigational therapy. Gilead also recently announced that the company is in the process of developing an investigational inhaled formulation of remdesivir to be used in patients with COVID-19.

A phase 2 study conducted with the NIH’s National Heart, Lung and Blood Institute shows fostamatinib, an oral spleen kinase (SYK) inhibitor from Rigel Pharmaceuticals, reduced the incidence of serious adverse events (SAEs) by half in hospitalized patients with COVID-19. The study randomized 30 patients to fostamatinib plus standard of care and 29 patients to placebo plus standard of care. At day 29, a total of three SAEs were reported in the fostamatinib arm compared with six events in the placebo plus standard-of-care group. There were no deaths in the fostamatinib arm by day 29, but three deaths were reported in the placebo group at the follow-up date. Treatment with fostamatinib was also associated with a more rapid reduction in the number of inflammatory markers compared with placebo.

A greater proportion of nonmechanically ventilated patients with severe COVID-19 who were treated with Kiniksa Pharmaceuticals’ investigational fully human monoclonal antibody mavrilimumab were alive and free of mechanical ventilation by day 29 in a phase 2 trial. The achievement of this primary endpoint was 12.3 percentage points higher in patients treated with mavrilimumab vs. placebo. Treatment with mavrilimumab was associated with a 65 percent reduction in the risk of mechanical ventilation compared with placebo, a difference that was statistically significant. Additionally, patients in the mavrilimumab arm experienced a 61 percent reduction in the risk of death. Based on positive data from this study, Kiniksa has started to enroll patients in a phase 3 portion of the trial. More than 250 patients are expected to participate in the late-stage study.

Initial results of a phase 3 clinical trial show treatment with investigational candidate NT-300 (300 mg nitazoxanide extended-release tablets) in patients with mild-to-moderate COVID-19 is associated with an 85 percent reduction in progression to severe disease. The multicenter trial included 1,092 people aged 12 years and older who had respiratory symptoms suggestive of COVID-19. Patients in this study were enrolled at outpatient centers in the U.S. within a 72-hour period from symptom onset. Participants received either two NT-300 tablets or placebo, both of which were administered twice daily for five days. Only 379 participants with laboratory-confirmed SARS-CoV-2 infection at baseline were included in efficacy analyses. A higher proportion of patients at high risk of severe illness progressed in their disease if they were treated with placebo vs. NT-300 (5.6 percent vs. 0.9 percent, respectively). Overall, NT-300 was well-tolerated. Romark Laboratories, the company investigating NT-300, expects to submit the full trial results to a peer-reviewed journal in the near future.

The NIH has launched a phase 2 study of IC14, an investigational monoclonal antibody from Implicit Bioscience. The study will evaluate the candidate’s ability to treat hospitalized patients with COVID-19 who present with respiratory disease and low blood oxygen levels. The trial, dubbed the COVID-19 anti-CD14 Treatment Trial (CaTT), is set to enroll 300 to 350 adults who have been hospitalized with COVID-19 at 10 to 15 centers in the U.S. Participants will be randomized to intravenous infusions of either placebo or IC14 for four days. All participants will also receive intravenous infusions of Gilead Sciences’ remdesivir for five consecutive days. Researchers will follow patients for up to 60 days to see if IC14 lowers the time needed for patients to recover from COVID-19-related respiratory disease and be discharged.

COVID-19 Vaccines:

Pfizer and BioNTech recently reported that their COVID-19 vaccine was 100 percent effective at preventing COVID-19 in 2,260 adolescents. The vaccine was capable of generating strong antibody responses and was well-tolerated. Investigators involved in this phase 3 study will follow participants for up to two years after their second dose. Given these positive findings, Pfizer and BioNTech have requested a revised Emergency Use Authorization from the FDA to allow its vaccine to be used in adolescents between 12 and 15 years of age. The two-dose vaccine is currently authorized in the U.S. for people age 16 years and older. The two companies said they will soon submit a similar revised authorization request to the European Medicines Agency, among other regulators across the globe.

Newly released data from a late-stage trial show Moderna’s COVID-19 vaccine is highly effective at preventing infection for up to six months after the second dose. The updated preliminary data from the phase 3 trial show the two-dose mRNA-1273 vaccine is more than 90 percent effective against COVID-19 infection and more than 95 percent effective against severe disease for up to six months. According to Moderna, the new data include more than 900 COVID-19 cases and more than 100 cases of severe COVID-19. The trial is ongoing, and the company says it plans to release further updates throughout the year. Additionally, Moderna says it hopes to release findings on the vaccine’s efficacy for preventing asymptomatic infection. Moderna may be close to filing for a biologics license application for its vaccine, considering the company seems to have met the FDA’s six-month requirement for additional study data.

An NIH trial is looking to determine whether highly allergic people or those with a mast-cell disorder are at an increased risk of sudden allergic reactions to the Pfizer-BioNTech or Moderna COVID-19 vaccines. The study is built on reports of rare, severe reactions in people with a history of allergies who have received the vaccines. Up to 3,400 people between 18 and 69 years of age will be enrolled in the new study, which will be conducted at up to 35 allergy research centers in the U.S. Approximately 60 percent of participants will be enrolled if they have a history of severe allergic reactions or a diagnosis with a mast-cell disorder. The remaining 40 percent of patients will not have a history of allergic reactions or a mast-cell disorder diagnosis. The investigators will randomize participants to receive either the Pfizer-BioNTech or Moderna vaccine or a placebo. Given that many allergic reactions to the vaccines have occurred in women, around two-thirds of the study cohort will consist of female participants. The researchers will investigate the biological mechanism underlying allergic reactions and will seek to identify predictive markers for these reactions. Findings from this study are expected to be available in late summer 2021.

Sinovac’s COVID-19 vaccine CoronaVac was 50.7 percent effective at preventing symptomatic COVID-19 in a phase 3 clinical trial in Brazil. The study included 9,823 healthcare workers who received the two-dose vaccine. A separate study from Brazil that involved more than 46,800 healthcare workers found that CoronaVac was 49.6 percent effective at reducing the risk of symptomatic infection in the two weeks following the first dose. The second study was conducted in a region where the P1 variant has been spreading rapidly. The efficacy rates of this vaccine are markedly lower than the mRNA vaccines from companies such as Moderna and Pfizer-BioNTech, both of which have shown their products to be more than 90 percent effective at preventing COVID-19.