Two cocktails of SARS-CoV-2-neutralising monoclonal antibodies for the COVID-19 prevention or therapy are in the rolling review process of the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA). The rolling review has begun for both Regeneron Pharmaceuticals Inc. and F. Hoffman-La Roche's Casirivimab/Imdevimab (REGN-COV2) combination and Eli Lilly's Bamlanivimab/Etesevimab antibody combination. The monoclonal antibodies bind to different epitopes of the SARS-CoV-2 spike protein, thus neutralising the virus and reducing new cell infection.
A medicine is granted an authorisation for the European market only after a complex evaluation process by the CHMP. This process usually takes longer than a year, including the time it takes for the applicant to respond to queries. During this process, data on the medicine’s quality, safety and efficacy are reviewed and evaluated. Now, the rolling review process is also being used for the cocktails of two SARS-CoV-2 neutralising monoclonal antibodies: Casirivimab/Imdevimab (REGN-COV2) and Bamlanivimab/Etesevimab. A rolling review is used to expedite COVID-19-related assessment procedures in particular, with a view to potential approval. For example, the evaluation of pharmaceutical and nonclinical development data packages starts before the full data on the clinical trial results are available for the formal regulatory submission.
The CHMP's decision to begin ongoing evaluation of the two antibody combinations is based on the reviews of preliminary results from laboratory studies as well as early clinical trials in adults.
The companies are currently conducting additional human clinical trials to determine the safety and efficacy of the neutralising monoclonal antibodies. As soon as sufficient data are available, the CHMP will review and evaluate them with respect to the benefit-risk balance. Ongoing review of additional data packages will continue until all data required for a formal marketing authorisation application are available.
The monoclonal antibodies Casirivimab, Imdevimab, Bamlanivimab and Etesevimab are IgG1 monoclonal antibodies that bind to the spike protein of SARS-CoV-2, blocking the interaction of viruses with the human ACE2 receptor. This inhibits and possibly prevents viral entry into human cells. The antibodies were isolated from specific immune cells from the blood of recovered patients. The antibodies are obtained in a special cell culture system, followed by numerous purification steps. The generation of human antibodies from COVID-19-genes and early clinical trial data indicate that efficacy can be expected. Furthermore, since these are antibodies that have already circulated in the human organism, a good safety profile can be assumed.
Both Casirivimab/Imdevimab and Bamlanivimab are already being used in Germany. This is made possible by the German Statutory Regulation on the Ensurance of Medical Supplies (Medizinischer Bedarf Versorgungssicherstellungsverordnung, MedBVSV). Drugs urgently needed in the SARS-CoV-2 epidemic can be procured by the Federal Ministry of Health (Bundesgesundheitsministerium, BMG) and used in the provision of care. The assessment of the Paul-Ehrlich-Institut was included in the BMG's decision on procurement and marketing. As stipulated in the regulation, the Paul-Ehrlich- Institut had determined with regard to these monoclonal antibodies that the quality is assured and its use is expected to have a positive benefit-risk ratio for the prevention or treatment of COVID-19 in certain patient groups based on the findings of medical science. Etesevimab has not yet been evaluated by the Paul- Ehrlich-Institut.
Updated: 11.03.2021
