C21 shows promise against COVID-19 where other drugs have failed

By Carl-Johan Dalsgaard, CEO of Vicore Pharma

The rapid development, and now distribution, of COVID-19 vaccines is welcome progress in the global fight against this pervasive and mutating virus. But we are far from being out of the woods yet. Recent data show that the Pfizer and Moderna vaccines are far less effective against the new South African strain than they are against the UK strain.¹ Vaccine-induced titres of neutralising antibodies show 6.5-8.3-fold reductions in those infected with the South African strain compared with those infected with the UK strain.¹

Across the world, hundreds of thousands of people are contracting this disease every day – on the 4th of February, there were 465,405 new cases² – with many of those in high-risk groups being admitted to hospital for specialist care. It is these patients who need effective drugs to beat the infection. A major effort is being put into testing existing drugs which have been repurposed as potential candidates to treat patients with COVID-19, and novel drugs are also in clinical trials for this purpose, including Vicore’s C21. In the US, President Joe Biden released an executive order on 21 January stating that they plan to put in place measures ‘to enhance the Nation’s ability to quickly develop the most promising COVID-19 interventions.’³ The urgency for this is clear.

Recent results for four leading repurposed drugs have been disappointing (only corticosteroids have shown clear benefit, mainly in more severe disease), while Vicore’s novel drug, C21, appears to show promise according to new data from the ATTRACT trial, soon to be published.

In the WHO Solidarity trial – the largest study at the time of repurposed drugs for COVID-19 – 11,330 adults with coronavirus infection at 405 hospitals in 30 countries were enrolled to investigate the therapeutic benefit of remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a.⁴ Unfortunately, the interim results indicate that all of the drug regimens appeared to have little or no effect on 28-day mortality. Furthermore, none of the drugs delayed the need for ventilation or shortened the stay in hospital.⁴

The latest data from Vicore’s ATTRACT (Angiotensin II Type Two Receptor Agonist in COVID-19 Trial) study are giving us cause for optimism, as the results show that C21 can restore respiratory function in COVID-19 patients.⁵ This randomised, double-blind, placebo-controlled, phase 2 trial was carried out between 21 July and 29 September 2020 at eight sites in India. Hospitalised patients aged 19-69 years with confirmed SARS-CoV-2 infection and with signs of acute respiratory infection, but not requiring invasive or non-invasive mechanical ventilation, were enrolled. A total of 106 patients were randomised to oral C21 (100 mg twice-daily) or placebo for 7 days, in addition to standard of care, including glucocorticoids and remdesivir.

The results were significant. C21 was well-tolerated, and at day 14 after the start of treatment, only one patient in the C21 group needed supplementary oxygen, compared with 11 patients in the placebo group – a reduction of 90%.⁵ In addition, only one patient on C21 required mechanical ventilation, compared with four patients on placebo. There were also fewer deaths in the C21 group: one, compared with three in the placebo group.⁵

As well as reducing the risk for extended need of supplementary oxygen, C21 may have prevented patients from progressing to more severe respiratory disease, as suggested by the lower proportion of patients requiring mechanical ventilation, and indeed the fewer deaths due to respiratory failure.

These data are very encouraging, and provide a firm foundation for a pivotal randomised controlled trial.

References

1. Evercore ISI. COVID: more evidence on the South African strain. 27 Jan, 2021
2. https://ourworldindata.org/grapher/daily-cases-covid-region?tab=table&time=2020-01-21..latest
3. The White House. Executive Order on Improving and Expanding Access to Care and Treatments for COVID-19. Presidential Actions. January 21, 2021. Available at: https://www.whitehouse.gov/briefing-room/presidential-actions/2021/01/21/executive-order-improving-and-expanding-access-to-care-and-treatments-for-covid-19/
4. WHO Solidarity Trial Consortium, et al. Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results. N Engl J Med. 2020 Dec 2:NEJMoa2023184. doi: 10.1056/NEJMoa2023184. Epub ahead of print.
5. Tornling G, et al. The angiotensin type 2 receptor agonist C21 restores respiratory function in COVID19 – a double-blind, randomised, placebo-controlled Phase 2 trial. 2021. In Press.