EU/3/13/1156

On 15 August 2013, orphan designation (EU/3/13/1156) was granted by the European Commission to CRO-PharmaNet Services GmbH, Germany, for recombinant human monoclonal antibody against hepatitis-B virus for the prevention of hepatitis-B re-infection following liver transplantation.

The sponsorship was transferred to inVentiv Health Germany GmbH, Germany, in July 2014.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What is hepatitis-B re-infection following liver transplantation?

Hepatitis B is an infectious disease that affects the liver, caused by the hepatitis-B virus. People who have been infected may not look or feel ill or may have mild flu-like symptoms, although some people can become very ill. Most people fully recover from the disease, but some remain infected (‘carriers’) and may go on to develop serious liver disease, such as cirrhosis (liver scarring) and liver cancer. If this happens, liver transplantation may be needed. However, since the virus is found in body fluids (such as blood) of hepatitis-B-virus carriers, the transplanted liver is likely to become infected in turn.

Hepatitis-B re-infection following liver transplantation is chronically debilitating and life-threatening because it may cause the transplanted liver to be damaged or rejected by the patient’s body.

What is the estimated number of patients at risk of developing the condition?

At the time of designation, the number of patients at risk of hepatitis-B re-infection following liver transplantation was estimated to be less than 0.1 people in 10,000 in the European Union (EU). This was equivalent to a total of fewer than 5,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

---

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 509,000,000 (Eurostat 2013).

What methods of prevention are available?

At the time of designation, several immunoglobulin preparations were authorised in the EU for the prevention of hepatitis-B re-infection following liver transplantation. In addition, antiviral medicines were also sometimes given.

The sponsor has provided sufficient information to show that recombinant human monoclonal antibody against hepatitis-B virus might be of significant benefit for patients at risk of hepatitis-B re-infection following liver transplantation, because early experimental studies have shown it to be effective against different types of hepatitis-B virus, including types that are difficult for the body’s natural defences to control and which are resistant to currently authorised immunoglobulin treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

This medicine is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a structure on the surface of the hepatitis-B virus called hepatitis surface antigen (HBsAg). By binding to the virus the medicine is expected to neutralise it and prevent it from re-infecting the cells of the transplanted liver.

The monoclonal antibody in this medicine is made by a method known as ‘recombinant DNA technology’: it is made by cells into which a gene (DNA) has been introduced that makes them able to produce the antibody.

What is the stage of development of this medicine?

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with recombinant human monoclonal antibody against hepatitis-B virus had been started in patients at risk of hepatitis-B re-infection after liver transplantation.

At the time of submission, the medicine was not authorised anywhere in the EU for prevention of hepatitis-B re-infection after liver transplantation. Orphan designation has been granted in the United States for prevention of hepatitis-B recurrence following liver transplantation.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 June 2013 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.