Remdesivir’s EU Approval For COVID-19 Due Within Days

Gilead Sciences’ Veklury (remdesivir) is expected to be approved in the EU for treating COVID-19 in a matter of days after the European Medicines Agency today decided that the product should be granted conditional marketing authorization (CMA).

The EMA’s decision to recommend approval for the investigational drug was made during the June meeting of the agency’s drug evaluation committee, the CHMP, which took place this week. (Also see "Remdesivir Races Through EU Review" - Pink Sheet, 22 Jun, 2020.)

The European Commission has the final say on authorization and will now fast-track its decision-making process. The EMA said the commission aimed to grant a decision on remdesivir’s approval “in the coming week, allowing the product to be marketed in the EU.”

Under the authorization, remdesivir, which is delivered intravenously, will be used to treat COVID-19 in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen – ie patients with severe disease.

A First In The EU For COVID-19

Remdesivir is the first medicine against COVID-19 to be recommended for authorization in the EU.

The antiviral drug is seen as one of the most promising potential therapies for COVID-19 and has already been made available under special mechanisms in countries including the US, Japan, and the UK.

The EMA evaluated the data on the product in an exceptionally short timeframe through a rolling review procedure, an approach the agency uses during public health emergencies to assess data as they become available.

A CMA will mean that Gilead will have to collect post-authorization evidence to support the approval.

Evaluating Effectiveness

The CHMP on 30 April began assessing data on quality and manufacturing, non-clinical data, preliminary clinical data and supporting safety data from compassionate use programs, well in advance of Gilead submitting its marketing authorization application on 5 June.

“The assessment of the dossier has now concluded with today’s recommendation, which is mainly based on data from study NIAID-ACTT-1, sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), plus supporting data from other studies on remdesivir,” the EMA said.

The NIAID-ACTT-1 study evaluated the effectiveness of a planned 10-day course of remdesivir in over 1,000 hospitalized patients with COVID-19. Remdesivir was compared with placebo and the main measure of effectiveness was patients’ time to recovery (defined as no longer being hospitalized and/or requiring home oxygen or being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care).

“Overall, the study showed that patients treated with remdesivir recovered after about 11 days, compared with 15 days for patients given placebo,” the EMA said. “This effect was not observed in patients with mild to moderate disease: time to recovery was 5 days for both the remdesivir group and the placebo group.”

For patients with severe disease, who constituted approximately 90% of the study population, time to recovery was 12 days in the remdesivir group and 18 days in the placebo group. However, no difference was seen in time to recovery in patients who started remdesivir when they were already on mechanical ventilation or ECMO (extracorporeal membrane oxygenation), the EMA said.

Data on the proportion of patients who died up to 28 days after starting treatment are currently being collected for final analysis.

Taking into consideration the available data, the EMA said it “considered that the balance of benefits and risks had been shown to be positive in patients with pneumonia requiring supplemental oxygen.”

Under the terms of the EU approval, the use of remdesivir will be limited to health care facilities where patients can be monitored closely. Liver and kidney function should be monitored before and during treatment, as appropriate. Treatment should start with a 200mg infusion on the first day, followed by one 100mg infusion a day for at least four days and no more than nine days.

Post-Approval Evidence

The CMA mechanism allows the EMA to recommend that a product be approved based on less complete data than would normally be expected, if the benefit of a medicine’s immediate availability to patients outweighs the risk inherent to the fact that not all the data are yet available.

In order to better characterize the effectiveness and safety of remdesivir, Gilead will have to submit the final reports of the remdesivir studies to the EMA by December 2020, and further data on the quality of the medicine, as well as the final data on mortality, by August 2020.

“As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of remdesivir once authorised across the EU,” the EMA said. “Further efficacy and safety data will be collected through on-going studies and post-marketing reports and will be regularly reviewed by the CHMP and EMA’s safety committee (PRAC). Since April 2020, the PRAC has also been reviewing safety data on patients treated outside clinical studies, which are being submitted as monthly safety reports; these will continue to be submitted and assessed after the medicine is on the market.”

During the assessment of remdesivir, the CHMP had the support of experts from the COVID-19 EMA pandemic task force (COVID-ETF). This was established to bring together the most relevant expertise from the European medicines regulatory network to assist member states and the commission in dealing with the development, authorization and safety monitoring of medicines and vaccines against COVID-19.