EU/3/12/1080: Orphan designation for the treatment of chronic lymphocytic leukaemia

4-(4-{[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (venetoclax)

Overview
Key facts
Review of designation

Overview

Please note that this product (marketed as Venclyxto) was withdrawn from the Community Register of designated orphan medicinal products in October 2018 upon request of the marketing authorisation holder at the time of the granting of a change to the terms of the marketing authorisation.

On 6 December 2012, orphan designation (EU/3/12/1080) was granted by the European Commission to AbbVie Ltd, United Kingdom, for 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide for the treatment of chronic lymphocytic leukaemia.

4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide has been authorised in the EU as Venclyxto since 5 December 2016.

The sponsorship was transferred to AbbVie Deutschland GmbH & Co. KG, Germany, in March 2018.

This medicine is now known as venetoclax.

: Chronic lymphocytic leukaemia (CLL) is cancer of a type of white blood cell called B-lymphocytes. In this disease, the lymphocytes multiply too quickly and live for too long, so that there are too many of them circulating in the blood. The cancerous lymphocytes look normal, but they are not fully developed and do not work properly. Over a period of time, the abnormal cells replace the normal white cells, red cells and platelets (components that help the blood to clot) in the bone marrow (the spongy tissue inside the large bones in the body).
CLL is the most common type of leukaemia and mainly affects older people. It is rare in people under the age of 40 years. CLL is a long-term debilitating and life-threatening disease because some patients develop severe infections.

: At the time of designation, CLL affected approximately 3 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 152,000 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 506,300,000 (Eurostat 2011).

: Treatment for CLL is complex and depends on a number of factors, including the extent of the disease, whether it has been treated before, and the patient's age, symptoms and general state of health. Patients whose CLL is not causing any symptoms or is only getting worse very slowly may not need treatment. Treatment for CLL is only started if symptoms become troublesome. At the time of designation, the main treatment for CLL was chemotherapy (medicines to treat cancer).
The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with CLL because it works in a different way to existing treatments and early studies show that it might improve the outcome of patients whose disease does not respond or has come back after previous treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

: This medicine is expected to work by blocking proteins called Bcl-2. These proteins allow cells to stay alive by preventing the natural process that leads to cell death (apoptosis). Bcl-2 proteins can be found in high concentration in cancer cells. By blocking the action of these proteins, the medicine is expected to make cancer cells more responsive to this natural process, causing their death and slowing the growth of the cancer. As Bcl-2 proteins have been shown to be associated with resistance to conventional chemotherapy, it is expected that this medicine will reduce resistance and allow other medicines to be more effective in their treatment.

: The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with CLL were ongoing.
At the time of submission, this medicine was not authorised anywhere in the EU for CLL. Orphan designation of the medicine has been granted in the United States for CLL.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 November 2012 recommending the granting of this designation.

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.

Key facts

Active substance	4-(4-{[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (venetoclax)
Medicine name	Venclyxto
Intended use	Treatment of chronic lymphocytic leukaemia
Orphan designation status	Withdrawn
EU designation number	EU/3/12/1080
Date of designation	06/12/2012
Sponsor	AbbVie Deutschland GmbH & Co. KG Knollstrasse 67061 Ludwigshafen Am Rhein Germany Tel. +49 621 589 3382 E-mail: eu-orphan-drug@abbvie.com

Review of designation

The Committee for Orphan Medicinal Products reviewed the orphan designation of Venclyxto at the time of marketing authorisation.

The sponsor formally requested the withdrawal of the orphan designation prior to the Committee’s final opinion. More information is available in the withdrawal assessment report – orphan maintenance .

On 14 October 2016, the Committee for Orphan Medicinal Products (COMP) completed the review of the designation EU/3/12/1080 for Venclyxto (venetoclax¹) as an orphan medicinal product for the treatment of chronic lymphocytic leukaemia. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with chronic lymphocytic leukaemia. The COMP recommended that the orphan designation of the medicine be maintained².

¹Previously known as 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide.

²The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with the same therapeutic indication cannot be placed on the market.

Documents related to this orphan designation evaluation

EU/3/12/1080 : Public summary of opinion on orphan designation: 4-(4-{[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-... (PDF/160.9 KB)

Adopted

First published: 25/01/2013
Last updated: 22/11/2018
EMA/COMP/720294/2012

Recommendation for maintenance of orphan designation at the time of marketing authorisation: Venclyxto (venetoclax) for the treatment of chronic lymphocytic leukaemia (PDF/94.62 KB)

Adopted

First published: 21/12/2016
Last updated: 22/11/2018
EMA/700601/2016

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.

EU register of orphan medicines

The list of medicines that have received an orphan designation in the EU is available on the European Commission's website:

European Commission: Community Register of orphan medicinal products