Paul-Ehrlich-Institut

Coronavirus and COVID-19

Biomedicines

Concurrent to the continuing development of preventive vaccines against COVID-19, scientists worldwide are also researching various medicines for COVID-19 treatment. Some of them have already received marketing authorisation and have been successfully used to treat other viral infections. All of these medicines must be scientifically evaluated for quality, safety and effectiveness.

Here is an overview of the different therapeutics:

Antibodies from persons who have recovered from a COVID-19 (convalescent plasma and hyperimmunoglobulins)

The administration of serum from COVID-19 recovered persons or of purified antibodies against SARS-CoV-2 (hyperimmunoglobulins) to those infected with the virus is a passive form of immunisation. The antibodies bind and neutralise the virus and thereby support the immune system in the fight against infection.

COVID-19 patients form antibodies specifically directed against SARS-CoV-2. The antibodies remain in their blood even after convalescence (recovery) accompanied by the elimination of the SARS-CoV-2 virus from their body. Blood plasma from COVID-19 recovered individuals containing these antibodies is therefore infused for therapy in persons with severe cases of COVID-19, with consideration to the patient’s blood type. It is also possible to isolate and concentrate antibodies from blood plasma in order to produce targeted immunoglobulins, which are also used for COVID-19 therapy. The prerequisite for plasma donation is that the former COVID-19 patient is proven to be recovered and virus-free and that their body has produced specific antibodies in sufficient quantities.

Clinical trials are imperative in order to assess this therapy in a structured manner and to develop it into applicable authorised medicinal products.

Mesenchymal stem cells

Mesenchymal stem cells are precursors to many different cell types in the human body. After a patient with a severe case of COVID-19 receives a transplant, the cells are meant to generate an anti-inflammatory effect, thus protecting healthy lung tissue and regenerating damaged lung tissue. In Germany, the production of these cells for use in humans always requires a manufacturing permit pursuant to must Good Manufacturing Practice (GMP).

Immunotherapy with monoclonal antibodies

Anti-inflammatory monoclonal antibodies bind to surface molecules on cells and interrupt intercellular and intracellular signalling pathways, e.g. via the interleukin-6 receptor. The aim is to prevent or inhibit an excessive immune response, which often is observed during the course of COVID-19.

On 7 December 2021, the European Commission extended the area of application for the monoclonal antibody RoActemra (tocilizumab) for the treatment of adults with severe COVID-19. Tocilizumab binds specifically to IL-6 receptors and inhibits IL 6R-mediated signal transduction and thus inflammatory reactions. A decrease in CRP levels to levels within the normal range was already observed on day 7 in COVID-19 patients treated with a dose of tocilizumab 8 mg/kg intravenously.

SARS-CoV-2 (neutralising) monoclonal antibodies

Several drugs with monoclonal antibodies and antibody combinations are available in Germany for the treatment or prophylaxis of COVID-19. Detailed information on neutralisation activity against variants of SARS-CoV-2 can be found in the product information of each drug.

The antibody combination casirivimab/imdevimab, which has now been authorised under the name Ronapreve, is available for treatment. However, it is not yet distributed via the usual distribution channels in Germany – via Roche Pharma AG or via pharmaceutical wholesale trade – but instead it is provided by the Federal Ministry of Health (BMG) within the framework of the Supply Assurance for Medical Needs Ordinance (Medizinischer Bedarf Versorgungssicherstellungsverordnung, MedBVSV) under the name Regn-CoV2. The drug composition of Regn-CoV2 corresponds to that of Ronapreve, which has been authorised in the EU since 12 November 2021. Regn-CoV2 should be used in accordance with the product information approved in the centralised European authorisation process. In vitro neutralisation assays of the monoclonal antibodies Ronapreve/Regn-CoV2 (casirivimab/imdevimab) show markedly reduced neutralisation activity against the Omicron variant of SARS-CoV-2 and indicate lower effectiveness.

The monoclonal antibody Regkirona (regdanvimab) from the company Celltrion has also been authorised in the European Union since 12 November 2021, but it is not yet available in Germany.

The monoclonal antibody Xevudy (sotrovimab) from the company GlaxoSmithKline (GSK) was authorised for COVID-19 therapy in the EU on 17 December 2021 and has been available in Germany since the end of January 2022.
Evusheld (tixagevimab and cilgavimab) is another monoclonal antibody combination for the pre-exposure prophylaxis of COVID-19. It has been available since the end of February 2022. This drug has been centrally authorised in the EU since 25 March 2022 and should be used according to the product information approved during the authorisation process. So far, Evusheld has not been distributed in Germany via the usual distribution channels – via AstraZeneca AB or via the pharmaceutical wholesale trade – but has instead been made available for use by certain groups of people in limited quantities by the BMG within the framework of the MedBVSV.

The monoclonal antibody combination Evusheld (tixagevimab and cilgavimab) maintained full to almost complete neutralisation activity against pseudovirus and/or live virus SARS-CoV-2 variant strains containing all spike amino acid substitutions that were identified in the variants Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Delta [+K417N] (AY.1/AY.2), and Omicron (BA.2). On the other hand, pseudotyped virus-like particles (VLP) expressing the spike protein and the authentic SARS-CoV-2 Omicron variant BA.1 (B.1.1.529) and Omicron BA.1.1 (B1.1.529 [+ R346K]) showed reduced neutralisation sensitivity to Evusheld (tixagevimab and cilgavimab). Pre-exposure prophylaxis with Evusheld is not a substitute for vaccination in individuals for whom COVID-19 vaccination is recommended.

The medicines Regn-CoV2 (Ronapreve, see above, casirivimab/imdevimab), Xevudy (sotrovimab) and Evusheld (tixagevimab/cilgavimab), which were procured centrally within the framework of the MedBVSV, continue to be dispensed via star and satellite pharmacies, which are listed on the website of the Robert Koch-Institut:

RKI - star and satellite pharmacies (authorised bodies according to § 2 paragraph 1 MedBVSV) (German only)

Further information on medicines procured centrally by the BMG can be found here:

RKI - General information on COVID-19 biomedicines (German only)

Reports of suspected adverse reactions to monoclonal antibodies against SARS-CoV2 should completed via the reporting form:

Reporting form - reporting suspected cases of side effects of monoclonal antibodies against SARS-CoV-2 (German only)

Further instructions for treatment with the different monoclonal antibodies are prepared by medical professional associations and STAKOB/COVRIIN The information is published on the RKI website:

RKI - COVID-19: Therapeutic information and recommendations (German only)

RKI - COVID-19: Provision of selected medicinal products by the BMG (German only)
German Federal Gazette - Announcement of the general ruling on the purchase and use of monoclonal antibodies and on the purchase and dispensing of antiviral oral medicinal products against COVID-19 (04.January 2022) (German only)
FAQ Vaccines and Biomedicines - Monoclonal Antibodies

Antivirals

Antivirals inhibit the activity, structure, and replication of the virus in the human body (e.g. protease inhibitors, RNA-polymerase inhibitors).

Further Information

Authorisation Granted for the Monoclonal Antibody Combination Evusheld (Tixagevimab and Cilgavimab) for COVID-19 Prevention
Use of Monoclonal Antibodies against COVID-19 – Xevudy (Sotrovimab) Available in Germany
Reduced Efficacy of Ronapreve (Casirivimab/Imdevimab) against Omicron Variant
European Commission grants EU Marketing Authorisations for SARS-CoV-2 Neutralising Monoclonal Antibodies Ronapreve (casirivimab/imdevimab) and Regkirona (regdanvimab)
CHMP Recommends Authorisation of SARS-CoV-2 Neutralising Monoclonal Antibodies Ronapreve (casirivimab/imdevimab) and Regkirona (regdanvimab) against COVID-19
EMA Ends Rolling Review for Bamlanivimab/Etesevimab Monoclonal Antibody Cocktail Following Withdrawal by Eli Lilly
Use of Monoclonal Antibodies against COVID-19
Monoclonal Antibody Cocktails against COVID-19 in Rolling Review
Paul-Ehrlich-Institut Approves First COVID-19 Therapy Study with Convalescent Plasma
RECOVER – the Paul-Ehrlich-Institut Authorises another COVID-19 Therapy Study with Reconvalescent Plasma
Recommendation of the Paul-Ehrlich-Institut for the Collection and Manufacture of COVID-19 Convalescent Plasma
Therapy against COVID-19 Symptoms under Development - Clinical Trials for Sarilumab authorised

Content

  1. Role of the Paul-Ehrlich-Institut
  2. COVID-19 Vaccines
  3. Proof of vaccination within the meaning of the Infection Protection Act (IfSG)
  4. FAQ Coronavirus
  5. Biomedicines
  6. Safety of COVID-19 Vaccines
  7. Research Work
  8. SARS-CoV-2 Test Systems