EU/3/05/314

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Orphan designation

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.

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

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).


*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.

Key facts

Product details for <p>(1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol</p>
Active substance(1R,2S) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol
Medicine Name
Disease/conditionTreatment of tuberculosis
Date of decision26/08/2005
OutcomePositive
Orphan decision numberEU/3/05/314

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.


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.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Sirturo for:

‘use as part of an appropriate combination regimen for pulmonary multidrug resistant tuberculosis in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability’.
This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of tuberculosis’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2005. Tuberculosis remains a condition that is debilitating in the long term and life threatening, particularly due to irreversible lung damage and the presence of drug resistant tuberculosis bacteria.

Prevalence of the condition

The sponsor provided updated information from tuberculosis surveillance in Europe from the European Centre for Disease Control (ECDC) and the World Health Organization (WHO).

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of tuberculosis in the EU remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was still estimated to be approximately 2 in 10,000. This is equivalent to a total of around 102,000 people in the EU.

Existence of other satisfactory methods of treatment

At the time of the review of the orphan designation, several other products were authorised in the EU for the treatment of tuberculosis either as combinations (e.g. ethambutol/isoniazid, isoniazide/rifampin and isoniazide/rifampin/pyrazinamide) or as products containing only one active substance (e.g. ethambutol, isoniazide, rifampin, pyrazinamide and streptomycin).

Significant benefit over existing treatments

The COMP concluded that the claim of a significant benefit of Sirturo in tuberculosis is justified on the basis of clinical study data on the effect of adding Sirturo to standard tuberculosis medicines in adults with multidrug resistant tuberculosis.

The data showed that adding Sirturo to standard treatment shortened the time needed for the tuberculosis bacteria to clear from the patients’ sputum (83 days versus 125 days in patients not given Sirturo). In addition, more patients who were given Sirturo in addition to standard treatments had negative sputum results after 24 weeks compared with those who were not given Sirturo (79% versus 58%) and the negative sputum results were sustained.

The COMP considered that the shorter time for the bacteria to clear from the sputum indicates that adding Sirturo to other treatments helps cure patients faster while also lowering the risk of the bacteria being transmitted to other people.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Sirturo is of significant benefit for patients affected by tuberculosis.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Sirturo still meets the criteria for designation as an orphan medicinal product and that Sirturo should remain in the Community Register of Orphan Medicinal Products.

Related information

Sponsor’s contact details

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium
Tel. +32 14 60 55 21
Fax +32 14 60 55 33

Patients' organisations

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

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