2 April 2020
The COVID-19 pandemic that has infected to date around 1,000,000 people worldwide presents an extraordinary challenge to global health. SARS-CoV-2 therapeutic candidates, including (repurposed) direct acting antivirals and immunomodulating agents are being considered and investigated.
The rapid spread of SARS-CoV-2 requires prompt development for therapeutic candidates to enter clinical trials; additionally, the need of developing pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) is being addressed.
During the second global regulatory workshop on 2 April 2020, delegates from 25 countries, representing more than 28 medicines regulatory authorities globally, and experts from the WHO and the European Commission discussed regulatory considerations related to the development of SARS-CoV-2 therapeutic candidates. The discussion was co-chaired by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) and the European Medicines Agency (EMA).
The meeting was structured around one presentation and a roundtable discussion between representatives of global medicines regulators.
The following represents generally agreed positions among global regulators in attendance.
Regulators emphasised that within the current COVID-19 disease pandemic, no specific medicinal product has yet clearly demonstrated efficacy. With the threat affecting all countries, regulators expressed the need for collecting robust and reliable evidence to establish safety and efficacy for the proposed medicines, so as to serve the patients’ needs in the fastest fashion possible.
Various therapeutic candidates have been prioritised for inclusion in large well-designed randomized clinical trials aimed at evaluating the treatment of COVID-19 patients. They include, based on a WHO-initiated landscape analysis of therapeutics, remdesivir, lopinavir/ritonavir with or without interferon–𝛽, and chloroquine/hydroxychloroquine. Other antivirals (e.g. monoclonal antibodies, hyperimmune sera) and immunomodulating agents such as IL-6 and IL-1 inhibitors are likewise considered for development.
However, for all these medicines, the pharmacological rationale, potential benefits and risks even in context of clinical trials, e.g. increased risk of infection with use, require careful attention.
It was agreed that randomised controlled trials (RCTs) with an appropriate control arm (i.e. not including antivirals or immune modulators), appropriately designed to generate data that meet regulatory requirements for approval, could lead to timely regulatory decisions, and could guide clinicians in defining promptly the best treatment options for COVID-19.
To this effect, multi-arm clinical studies investigating different agents simultaneously have the potential to deliver results as rapidly as possible across a range of therapeutic options, according to the same evaluation criteria.
Participants acknowledged that small studies or compassionate use programmes are unlikely to be able to generate the required level of evidence to allow clear-cut recommendations.
Nevertheless, regulators concurred that compassionate use programmes, which allow access to potential therapies for patients in need, have a beneficial public health impact on the pandemic and should be allowed, as long as they do not pose a threat to clinical trials recruitment.
Regulators expressed concern due to the multitude of ongoing trials and access programmes, which may lead to shortages of investigational products, and recommended this to be carefully monitored. It was acknowledged that preservation of access to medicines approved in indications other than COVID-19 and used as well in COVID-19 investigations might be critical in these situations, posing ethical issues of equitable distribution.
It was agreed that as clinical trial data emerge from relevant studies, sharing of information would be of uttermost importance globally. This group will reconvene within 2-3 months to take stock of the evolving therapeutic landscape.
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