Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

The antiviral remdesivir - an example of expedited approval procedures in the USA within the Covid-19 pandemic ***

Francesca Haaf (Abschlußjahr: 2021)

Summary
Language: English
The COVID 19 pandemic has challenged researchers worldwide to find a treatment of SARS COV 2 virus as quickly as possible. The research focus has been on direct-acting antiviral drugs. Based on the example of the antiviral remdesivir, this thesis shows which expedited regulatory pathways exist in the USA to make new or repurposed drugs available to patients before approval or to approve them in order to counteract the pandemic.
Concerning the regulatory background for the development of antivirals in the USA the FDA has issued several antiviral guidance documents. One basic guidance was issued 2006. Two COVID 19 specific guidances were published, one of them concerns drug development with a focus on antivirals. The FDA has also established the Coronavirus Treatment Acceleration Program (CTAP), providing direct contact between developers and the relevant FDA department. For comparison, the EMA has also released guidance and an initiative for the development of treatments against COVID-19.
There are several potential targets of antivirals in the life-cycle of SARS-COV-2 virus. Remdesivir’s mechanism of action is to inhibit RNA-dependent RNA polymerase (RdRP).
It is a repurposed drug that had already been clinically tested against Ebola virus disease. It was possible to refer back to the nonclinical and clinical trials with remdesivir for this disease and soon start testing its antiviral activity against SARS COV 2 and also to rapidly initiate phase III trials for COVID 19. To date there have been five important phase III trials with remdesivir. Three of them led to approval of remdesivir in the USA in October 2020 for the treatment of COVID 19 in patients requiring hospitalisation.
In addition to the requirements for antiviral development early access to investigational drugs and expedited approval pathways had already been in place in the USA. These are intended, among others, for drugs for the needs in a public health emergency. Early access to remdesivir even before and during clinical trials was initially made possible by "Expanded Access", which was then replaced by the "Emergency Use Authorisation". One expedited approval procedure applied for remdesivir was the "Fast-track Designation", with the benefits of more intensive communication with the FDA and a "Rolling review" by submitting parts of the NDA (New Drug Application) that are reviewed by FDA as they come in. Another one was the "Priority review" of the remdesivir NDA, that reduced the review time by FDA to barely 3 months after the last NDA section was submitted instead of the standard 10 months. The early access to investigational drugs or accelerated approval pathways available in the EU were briefly compared.
The development of remdesivir and its approval in the USA was directed by general and COVID 19 specific antiviral guidelines and programs as well as existing regulatory mechanisms enabling early access of remdesivir during clinical trials and expedited regulatory pathways already available.
In order to have an even faster availability of drugs in a pandemic, the exchange between the FDA and the EMA could be intensified, scientific data could be shared and the review of certain submitted data could be split between the FDA and the EMA.
Pages: 73