JAKARTA (TheInsiderStories) – In the absence of a vaccine, effective therapeutics for COVID-19 and its complications are urgently being sought to help mitigate the most serious consequences of infection and to reduce the duration of virus shedding and infectivity. This is especially important since the timeline for approval of a repurposed known medicine would be much shorter than that for a vaccine, since basic safety should already be established.
There has been a major research effort worldwide, with hundreds of trials and investigations having been initiated for a wide range of existing and novel compounds, although success so far has been relatively limited. IHS Markit has evaluated current evidence and status for a selection of promising medicines, together with current high-profile anti-viral, that are under evaluation for COVID-19 infection and its complications.
Many of the drugs under the closest scrutiny currently are repurposed versions of existing medicines that have established safety profiles and could be approved relatively quickly, once the evidence base is confirmed to be adequate. Medicines that are currently receiving are highly likely to be superseded by more effective products – some with similar mechanisms – as results from controlled trials become available.
Latest developments for COVID-19 therapeutics in the week ending 16 July are Australia’ Therapeutic Goods Administration has granted provisional approval to Gilead Sciences (US)’ remdesivir for hospitalised adults and adolescents with severe COVID-19 symptoms. The approval, which was based on preliminary clinical data, is the country’s first for a COVID-19 treatment.
A comparative analysis of data from the SIMPLE-Severe clinical trial versus a real-world retrospective cohort of patients has suggested that Veklury (remdesivir) treatment was associated with an improvement in clinical recovery and a 62 percent reduction in the risk of mortality compared with standard of care. Furthermore, 74.4 percent of patients treated with Veklury recovered (on a seven-point scale) by day 14, compared with 59.0 percent of the standard-of-care cohort (defined as improvement in clinical status on a seven-point scale).
Researchers in Japan have reported “inconclusive results” from a completed trial investigating Fujifilm (Japan)’s Avigan (favipiravir) as a treatment for COVID-19. While patients receiving the drug early in the trial showed more improvement that those treated following a delay, the results did not reach statistical significance.
The trial enrolled 89 patients across Japan between March and May 2020. Progress of the trial had been delayed because of a shortage of patients in Japan, although versions of favipiravir have already been approved for treatment in countries such as India and Russia. There are 25 trials still in progress, investigating favipiravir for COVID-19, and the Russian developer of the Avifavir version, ChemRar, has claimed that data from its own trials may indicate significant efficacy.
Positive results have been reported for repurposed IL6 inhibitor Actemra (tocilizumab; Roche, Switzerland) in peer-reviewed results from a 154-patient controlled US trial, reported in Clinical Infectious Diseases. In the trial, mechanically ventilated COVID-19 patients who received a single intravenous dose of Actemra showed 45 percent reduced risk of death versus controls.
In addition, patients who had received Actemra were more likely than controls to have been discharged from hospital or removed from a ventilator one month after treatment. However, Actemra treatment was associated with a risk of additional infections in ventilated patients, despite the lower mortality findings.
A new study by Dutch researchers has indicated a potential risk in the therapeutic use of convalescent plasma from patients who have had severe COVID-19. In plasma from certain patients, elevated levels of an anti-spike IgG antibody with aberrant glycosylation were detected, and this antibody type was linked with the stimulation of dangerous hyper-inflammatory responses in recipients.
These results suggested that plasma donations from severe patients could be too risky to use in hospitalised patients and would need to be screened carefully. However, the authors have also found that this could be reversed in vitro with a Syk inhibitor, such as the approved product fostamatinib, which is about to enter a trial for other COVID-19 complications.
The repurposed Syk inhibitor Tavalisse (fostamatinib; Rigel, US), currently used to treat thrombocytopenia, is entering an investigator-sponsored clinical trial at Imperial College London to evaluate efficacy for the treatment of COVID-19 pneumonia.
Tavalisse was isolated from a mass screening for compounds that decreased MUC1 levels, indicating potential in treating COVID-19-related lung injury. It preferentially depleted MUC1 from epithelial cells in vitro without affecting cell viability. Additionally, in a separate study in vitro, Tavalisse reversed the hyper-inflammatory effect of abnormally glycosylated anti-spike IgG antibodies found in convalescent plasma from severely ill COVID-19 patients.
The repurposed plaque psoriasis drug Alzumab (itolizumab) from Biocon Biologics (India) has received emergency accelerated approval in India for the treatment of cytokine release syndrome (CRS) in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) because of COVID-19. It is an anti-CD6 IgG1 monoclonal antibody.
Twenty-three COVID-19 vaccine candidates are currently in clinical trials (as of 16 July), and these and other promising candidates are listed in the table below. To date, three vaccine candidates from AstraZeneca (UK), Sinovac and Sinopharm (China) have entered Phase III development, three are in Phase II, and several more are in Phase I/II and Phase I. The success of any of these will depend on safety, level of immunogenicity, and duration of protection.
“We expect the most dramatic developments in the R&D landscape here not to come from remdesivir, hydroxychloroquine, or other repurposed treatments, although we do see a critical role for existing treatments being repositioned to deal with the various effects of COVID-19,” said IHS Markit.
by Gustav Ando and Janet Beal from IHS Markit