Where are we in the development process?
Words By Eleanor Deane
The COVID-19 online clinical trials tracker reports the thousands of trials currently investigating treatments for COVID-19 and fiercely racing for a vaccine. On 11 August 2020, Russia became the first country in the world to approve a vaccine for the novel coronavirus, although since then only phase 1/2 results (76 participants) have been published.
Vaccines must pass through 3 phases of clinical trials before being assessed for regulatory review and approval. ‘Ad5-nCoV’ is a vaccine being tested in trials in China. Results from phase 1 trials showed the vaccine was able to cause an immune response in most participants, without serious side effects. Phase 2 trials were also positive, and it has been announced that phase 3 trials have been initiated. A further vaccine, known as ‘AZD1222’, is a vaccine that carries the COVID-19 spike protein. A phase 3 trial in the UK was provisionally halted in September due to an adverse reaction. The trial has since been reinstated following regulatory approval.
Currently, moderate and severe cases are largely managed in hospitals by supporting symptoms, using previous knowledge of supporting patients with severe infections. Results from the RECOVERY trial have informed the use of the corticosteroid Dexamethasone in patients with severe COVID-19.
One of the potential treatments with many trials ongoing is convalescent plasma. Plasma is a component of blood that is rich in antibodies – the molecules that combat viruses. In the treatment of COVID-19, convalescent plasma would be the plasma of someone that had previously been infected with covid. This means that people who have had coronavirus can register to support these trials by donating their plasma. A meta-analysis and systematic review which included 5444 patients found some evidence of reduced mortality, however, the evidence is of limited quality. Due to the current limitations of studies, the National Institute of Health judges the evidence insufficient to recommend convalescent plasma in their guidelines.
Hydroxychloroquine and chloroquine are two drugs which are used in malaria treatment and have shown some activity against coronavirus at the laboratory stage. However, a systematic review of the literature published in late August shows that there is little evidence to support the use of these drugs. This has led to the discontinuation of hydroxychloroquine in several trials including the UK RECOVERY trial.
Lopinavir/ritonavir is one of a class of drugs known as protease inhibitors which are used in certain treatment regimens for HIV. Results from the UK RECOVERY trial did not find a benefit in terms of mortality or progression to ventilation. However, there is some evidence to suggest Lopinavir/ritonavir may reduce time to symptom resolution.
The process by which drugs move through clinical trials is slow, with many vaccines having taken 10 to 15 years to develop. This largely due to the logistics of clinical trials and the need to adequately prove both safety and efficacy. The number of trials focused on coronavirus will hopefully accelerate this timeline. Undoubtedly, alternative methods of prevention such as the use of face coverings, screening and distancing have a vital part to play in the meantime.