Decision

Summary of the Public Assessment Report for Ronapreve

Updated 19 November 2021

The Public Assessment Report summarises the initial assessment at the time of approval in August 2021. The text in the original report remains unchanged.

Our advice is regularly updated on the basis of significant new data and our latest advice can be found in the Summary of Product Characteristics.

1. Lay Summary Ronapreve 120 mg/mL solution for injection or infusion

casirivimab, imdevimab

This is a summary of the Public Assessment Report (PAR) for Ronapreve 120 mg/mL solution for injection or infusion. It explains how this product was assessed and its authorisation recommended, as well as its conditions of use. It is not intended to provide practical advice on how to use this product.

This product will be referred to as Ronapreve in this lay summary for ease of reading.

For practical information about using Ronapreve, patients should read the Patient Information Leaflet (PIL) or contact their doctor or pharmacist.

1.1 What is Ronapreve and what is it used for?

This application is a full-dossier application. This means that the results of pharmaceutical, non-clinical and clinical tests have been submitted to show that this medicine is suitable for treating the specified indications.

Ronapreve is used to treat patients with confirmed acute Covid-19 infection and to prevent acute Covid-19 infection.

1.2 How does Ronapreve work?

Ronapreve is a combination of two active substances ‘casirivimab’ and ‘imdevimab’. Casirivimab and imdevimab are a type of protein called ‘monoclonal antibodies’. Casirivimab and imdevimab bind to part of the spike protein receptor binding domain (RBD) of SARS-CoV-2. Casirivimab and imdevimab, individually and combined, block RBD binding to the human angiotensin converting enzyme-2 (ACE2) receptor thereby preventing SARS-CoV-2 from entering human cells and consequentially stopping Covid-19 infection.

Ronapreve is intended to compensate/substitute for endogenous antibodies in those individuals who have yet to mount their own immune response to block infection.

1.3 How is Ronapreve used?

This medicine is a solution for injection/infusion (sterile concentrate) and the route of administration is intravenous infusion or subcutaneous injection.

The dosage is 600 mg of casirivimab and 600 mg of imdevimab administered together either as a single intravenous (IV) infusion via pump or gravity (where the pressure of gravity delivers Ronapreve into the IV line at a steady and safe rate using a manually operated clamp) or by subcutaneous (SC) injection.

Casirivimab and imdevimab should be given concurrently as soon as possible following exposure to SARS-CoV-2.

For individuals who require repeat dosing for ongoing prevention, i.e. those who have a medical condition making them unlikely to respond to or be protected by vaccination:

• the initial dose is 600 mg of casirivimab and 600 mg of imdevimab by IV infusion or SC injection.
• subsequent doses are 300 mg of casirivimab and 300 mg of imdevimab by IV infusion or SC injection once every 4 weeks.
• repeat dosing regimens for prevention of Covid-19 allow for switching from IV infusion to SC injection or vice versa over the course of treatment.

The rate of infusion may be slowed, interrupted or discontinued if the patient develops any signs of infusion-associated events or other adverse events.

Doses should not be missed and the dosing regimen should be adhered to as closely as possible. If a dose of Ronapreve is missed it should be administered as soon as possible. The schedule of administration should be adjusted to maintain the appropriate interval between doses.

The safety and efficacy of Ronapreve in children < 12 years of age has not yet been established and no data are available. No dosage adjustment is recommended in paediatric individuals ≥ 12 years of age and older and weighing ≥ 40 kg.

For further information on how Ronapreve is used, refer to the Patient Information Leaflet (PIL) and Summary of Product Characteristics (SmPC) available on the Medicines and Healthcare products Regulatory Agency (MHRA) website.

This medicine can only be obtained with a prescription.

The patient should ask the administering healthcare practitioner if they have any questions concerning the medicine.

1.4 What benefits of Ronapreve have been shown in studies?

In Study COV-20145 Ronapreve was studied in adult outpatients with SARS-Cov-2 infection following a single IV or single subcutaneous dose of Ronapreve. Patients who took Ronapreve had a statistically significant reduction in viral load compared to placebo. The largest reductions in viral load relative to placebo were measured in patients with high viral load.

In Study COV-2067 Ronapreve was studied in adult outpatients with Covid-19 infection who received doses of Ronapreve up to 7 times the recommended dose. All patients had at least one risk factor for severe Covid-19. Patients who took Ronapreve had a 70% relative risk reduction in Covid-19-related hospitalisation or death compared to placebo. The median time to symptom resolution for patients who took Ronapreve was 10 days compared with 14 days for placebo.

In Study COV-2069 Ronapreve was studied in adult patients with a negative Covid-19 RT-PCR test result at enrolment into the study. Patients who took Ronapreve had an 81% relative risk reduction in the development of Covid-19 compared to placebo.

In the same study, Ronapreve was studied in asymptomatic adult patients with a positive Covid-19 RT-PCR test at enrolment into the study. Patients who took Ronapreve had 35% relative risk reduction in the development of Covid-19 compared to placebo.

In Study HV-2093 the effects of repeat SC doses (up to 6 monthly doses) of Ronapreve were studied in adult patients who were not infected with Covid-19 at the point of enrolment. During the 6-month period, patients who took Ronapreve had a 92% relative risk reduction in Covid-19 versus placebo.

1.5 What are the possible side effects of Ronapreve?

The most common side effects with Ronapreve (which may affect more than 1 in 10 people) are redness, itching, bruising, swelling, pain or itchy rash at the injection site. For the full list of all side effects reported with this medicine, see Section 4 of the PIL or the SmPC available on the MHRA website.

If a patient gets any side effects, they should talk to their doctor, pharmacist or nurse. This includes any possible side effects not listed in the product information or the PIL that comes with the medicine. Patients can also report suspected side effects themselves, or a report can be made on behalf of someone else they care for, directly via the Yellow Card scheme at www.mhra.gov.uk/yellowcard or search for ‘MHRA Yellow Card’ online. By reporting side effects, patients can help provide more information on the safety of this medicine.

1.6 Why was Ronapreve approved?

Ronapreve has been shown to be effective in the treatment of patients with confirmed acute Covid-19 infection and to prevent acute Covid-19 infection. Furthermore, the side effects observed with use of this product are considered to be typical for this type of treatment. Therefore, the MHRA decided that the benefits are greater than the risks and recommended that this medicine can be approved for use.

Ronapreve has been authorised with a Conditional Marketing Authorisation (CMA). CMAs are intended for medicinal products that address an unmet medical need, such as a lack of alternative therapy for a serious and life-threatening disease. CMAs may be granted where comprehensive clinical data is not yet complete, but it is judged that such data will become available soon.

1.7 What measures are being taken to ensure the safe and effective use of Ronapreve?

All new medicines that are approved have a Risk Management Plan (RMP) to ensure they are used as safely as possible. A Risk Management Plan (RMP) has been agreed for Ronapreve in the UK. Based on this plan, safety information has been included in the SmPC and the PIL, including the appropriate precautions to be followed by healthcare professionals and patients.

All side effects reported by patients/healthcare professionals are continuously monitored. Any new safety signals identified will be reviewed, and if necessary, appropriate regulatory action will be taken. To facilitate timely patient access to treatment, the MHRA has approved a batch specific variation for cartons of ‘casirivimab and imdevimab 120 mg/ml concentrate for solution for infusion’, which have been used around the world during the Covid-19 pandemic, for use in the UK under the conditions required for Ronapreve 120 mg/ml solution for injection or infusion. A Direct Healthcare Professional Communication (DHPC) has been agreed as part of this variation to highlight the difference between the labels approved as part of the PLGB conditional marketing authorisation and pandemic labels.

1.8 Other information about Ronapreve

A Conditional Marketing Authorisation for Ronapreve was granted in Great Britain (GB, consisting of England, Scotland and Wales) on 19 August 2021. A Regulation 174 is in place to supply Northern Ireland (NI).

The full PAR for Ronapreve is available here.

This summary was last updated in November 2021.