EU/3/05/314 - orphan designation for treatment of tuberculosis

(1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol bedaquiline

Overview

On 26 August 2005, orphan designation (EU/3/05/314) was granted by the European Commission to Tibotec Pharmaceuticals Ltd., Ireland, for (1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol for the treatment of tuberculosis.

The sponsorship was transferred to Tibotec BVBA, Belgium, in December 2008 and to Janssen-Cilag International N.V., Belgium, in September 2012.

(1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol has been authorised in the EU as Sirturo since 5 March 2014.

This medicine is now known as bedaquiline.

What is tuberculosis?

Tuberculosis is an infection caused by a group of bacteria called Mycobacterium. It spreads from person to person by inhaling the infected airborne droplets generated by sneezing and coughing. The manifestation of the disease is variable and not all patients who are infected will develop the disease. The disease is characterised by fever, cough and breathing difficulties. Granulomas (accumulations of large numbers of cells leading to chronic inflammatory lesions) can develop in any body tissue, but most often in the lungs (pulmonary tuberculosis) but can also affect the central nervous system (meningitis), lymphatic system, genitourinary system, bones and joints. Tuberculosis is a life-threatening condition.

What is the estimated number of patients affected by the condition?

At the time of designation, tuberculosis affected not more than 2 in 10,000 people in the European Union (EU)*. This was equivalent to a total of not more than 92,000 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).

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*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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 466,600,000 (Eurostat 2005).

What treatments are available?

Treatment consists of the administration of a combination of antibiotics for long periods of time.

Several medicinal products were authorised for the condition in the Community at the time of submission of the application for orphan designation. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that (1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol might be of potential significant benefit for the treatment of tuberculosis mainly because it might improve the long-term outcome of the patients. The assumption of benefit will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

(1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol is, according to the sponsor, an antimycobacterial agent. It acts by blocking (inhibiting) a protein involved in the energy generation of the mycobacteria and this could potentially kill the microorganisms themselves.

What is the stage of development of this medicine?

The effects of (1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with tuberculosis were ongoing.

(1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol was not authorised anywhere worldwide for the treatment of tuberculosis or designated as an orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted a positive opinion on 13 July 2005 recommending the granting of the above-mentioned designation.

Update: (1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol (Sirturo) has been authorised in the EU since 05 March 2014. Sirturo is indicated for use as part of an appropriate combination regimen for pulmonary multidrug resistant tuberculosis (MDR TB) in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. Consideration should be given to official guidance on the appropriate use of antibacterial agents.

More information on Sirturo can be found in the European public assessment report (EPAR).

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 Community) 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.

EU/3/05/314: Public summary of positive opinion for orphan designation of (1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol for the treatment of tuberculosis

AdoptedReference Number: EMA/COMP/247350/2005 Rev.4

Key facts

• Active substance:
  (1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol bedaquiline
• Medicine name:
  Sirturo
• Intended use:
  Treatment of tuberculosis
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/05/314
• Date of designation:
  26/08/2005
• Sponsor:

  Janssen-Cilag International NV; Turnhoutseweg 30; B-2340 Beerse; Belgium; Tel. [phone]; Fax [phone]

Review of designation

During its meeting of 7 to 9 January 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/05/314 for Sirturo (bedaquiline)¹ as an orphan medicinal product for the treatment of tuberculosis. 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 satisfactory methods of treatment. As other methods of treatment for patients with this condition are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designation of the medicine be maintained².

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¹Previously known as (1R,2S)6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol.
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 a comparable therapeutic indication cannot be placed on the market.