FDA Decision Alerts March 16, 2021
CDER-Approved NDA for VEKLURY® (remdesivir)
On October 22, 2020, the FDA approved Gilead Sciences’s VEKLURY® (remdesivir) for the “treatment of coronavirus disease 2019 (COVID-19) requiring hospitalization” in patients 12 years of age and older. Of note: Gilead received Priority Review and Fast Track designations as well as a Material Threat Medical Countermeasure Priority Review Voucher.
One randomized controlled trial (RCT), ACTT-1 (NCT04280705, n=1,062) and two randomized, open-label trials—GS-US-540-5774 (NCT04292730, n=1,113) and GS-US-540-5773 (NCT04292899, n=4,891)—provided substantial evidence of efficacy. The applicant also submitted emergency use authorization (EUA) data, expanded access program data, and four additional studies (three RCTs and one open-label mass-balance study) as additional evidence of safety and efficacy.
Emergency Use Authorization
Intent of the RWE study: The applicant submitted EUA data to support remdesivir’s safety profile. The FDA issued an EUA for remdesivir on May 1, 2020, and revised the EUA on August 28, October 1, and October 16, 2020.
Protocols for RWE generation: The applicant collected EUA data in accordance with the terms of the authorization. The EUA data provided information on medication errors and adverse events (AEs), including death and serious AEs.
Outcome of the RWE submissions: The Office of Surveillance and Epidemiology (OSE) conducted two reviews of the available safety data related to EUA use of remdesivir. On July 9, 2020, OSE identified 402 FDA Adverse Event Reporting System (FAERS) case reports. Of those 402 cases, 114 (28%) reported elevated transaminase levels. The FDA could not establish a causal link between remdesivir and this AE due to confounders such as underlying comorbidities, concomitant medications, and liver injury occurring in COVID-19 patients. OSE conducted another review on August 28, 2020, finding 600 cases of potential hepatotoxicity, none of which were non-confounded. The FDA’s review of relevant literature confirmed a potential hepatotoxicity safety signal.
The FDA identified multiple additional AEs in the EUA population, including administration site extravasation, rash, anaphylaxis, angioedema, infusion-related reactions, and hypersensitivity. Remdesivir’s label notes these AEs occurred in the EUA population.
Expanded Access Program
Intent of the RWE study: The applicant submitted expanded access data to support the safety profile of remdesivir.
Protocols for RWE generation: The applicant’s expanded access program included 163 adult patients who received remdesivir from January 26 to March 14, 2020. The program data also included a number of pregnancy cases and adolescent data (39 patients between 12 and 18 years of age received the drug from March 21 to April 22, 2020).
Outcome of the RWE submissions: The FDA considered the expanded access data, but concluded that it should not be used to assess remdesivir’s safety and efficacy due to limited available clinical data. Remdesivir’s label notes the pediatric and pregnancy data (n=122) were insufficiently detailed to allow for evaluation in those populations.
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