EU/3/10/826

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Orphan designation

On 17 December 2010, orphan designation (EU/3/10/826) was granted by the European Commission to Lucane Pharma SAS, France, for para-aminosalicylic acid for the treatment of tuberculosis.

The sponsorship was transferred to Lucane Pharma SA, France, in February 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 (TB) is an infectious disease caused by bacteria called Mycobacterium tuberculosis. People become infected by inhaling infected droplets from the cough or sneeze of people who have the disease. TB primarily affects the lungs (when it is called pulmonary TB) but it can also spread to other parts of the body, such as the bones or the nervous system. The symptoms of TB include persistent cough, fever, weight loss and night sweats. Not everyone infected will develop the symptoms of the disease.

TB is a long-term debilitating disease. When left untreated, the disease may be life-threatening, mainly because of the severe damage to the lungs that does not allow the patient to breathe normally, and because the bacteria causing the disease are often resistant to existing treatments.

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

At the time of designation, TB affected approximately 2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 101,000 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. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

What treatments are available?

At the time of designation, several antibiotics were authorised in the EU to treat TB. These were used in combination and for long periods of time, normally at least six months.

The sponsor has provided sufficient information to show that para-aminosalicylic acid might be of significant benefit for patients with TB because it is expected to improve the treatment of patients with TB that is resistant to many other medicines, and because it will be available as a gastroresistant granule formulation that is expected to cause fewer side effects. These assumptions 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?

Medicines containing para-aminosalicylic acid have been used in combination with other medicines to treat TB since the 1940s. Para-aminosalicylic acid is a ‘bacteriostatic’. This means that it prevents the bacteria from growing and multiplying without actually killing them. It does this by blocking the synthesis (manufacture) of folic acid, which the bacteria need to grow and multiply, and of mycobactin, a component of their cell wall. These actions have the effect of stopping the growth of bacteria also in patient with TB that is resistant to other antibiotics like streptomycin and isoniazid.

In this medicine, para-aminosalicylic acid is expected to be available as gastroresistant granules that allow the para-aminosalicylic acid to reach the intestine without being released in the stomach, thus avoiding irritation in the stomach and causing fewer side effects.

What is the stage of development of this medicine?

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

At the time of submission of the application for orphan designation, clinical trials with para-aminosalicylic acid in patients with TB had finished.

At the time of submission, para-aminosalicylic acid was authorised in the United States and Russia for TB.

At the time of submission, the medicine was not authorised anywhere in the EU for TB. Orphan designation of para-aminosalicylic acid for TB had been granted in the United States.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 October 2010 recommending the granting of this designation.

Update: para-aminosalicylic acid (Para-aminosalicylic acid Lucane) has been authorised in the EU since 7 April 2014 for use as part of an appropriate combination regimen for multi-drug resistant tuberculosis in adults and paediatric patients from 28 days of age and older when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.

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.

Name Language First published Last updated
EU/3/10/826: Public summary of opinion on orphan designation: Para-aminosalicylic acid for the treatment of tuberculosis (English only) 20/01/2011 19/06/2014

Key facts

Product details for <p>Para-aminosalicylic acid</p>
Active substancePara-aminosalicylic acid
Medicine NamePara-aminosalicylic acid Lucane
Disease/conditionTreatment of tuberculosis
Date of decision17/12/2010
OutcomePositive
Orphan decision numberEU/3/10/826

Review of designation

During its meeting of 4 to 6 February 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/10/826 for Para-aminosalicylic acid Lucane (para-aminosalicylic acid) 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 maintained1.


1 The 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 Para-aminosalicylic acid Lucane for:

‘use as part of an appropriate combination regimen for multi-drug resistant tuberculosis in adults and paediatric patients from 28 days of age and older 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 2010. Tuberculosis remains a condition that is debilitating in the long term and life threatening, particularly due to the irreversible lung damage that can occur and the fact that some tuberculosis bacteria are resistant to existing treatments.

Prevalence of the condition

The sponsor provided data from population-based studies in Europe obtained by the European Centre for Disease Control (ECDC) and the World Health Organisation. On the basis of these data and the knowledge of the COMP, the COMP concluded that the prevalence of tuberculosis 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 estimated to be approximately 1.4 people in 10,000. This is equivalent to a total of around 72,000 people in the EU.

Existence of other satisfactory methods of treatment

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

Significant benefit over existing treatments

The COMP concluded that the claim of a significant benefit of Para-aminosalicylic acid Lucane in tuberculosis is justified on the basis of data from the literature showing the benefits of the active substance, para-aminosalicylic acid, when used in combination with other medicines to treat multi-drug resistant tuberculosis. This was supported by additional data showing that Para-aminosalicylic acid Lucane was effective in clearing the tuberculosis bacteria in patients’ sputum, including in patients with tuberculosis that was resistant to other treatments.

Medicines containing para-aminosalicylic acid had been widely used in the past but were largely discontinued due to adverse effects on the stomach. Para-aminosalicylic acid Lucane contains gastro-resistant granules, designed to allow para-aminosalicylic acid to reach the intestine without being released in the stomach, and thus reduce the potential for side effects.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Para-aminosalicylic acid Lucane 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 Para-aminosalicylic acid Lucane still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Sponsor’s contact details

Lucane Pharma SA
172 rue de Charonne
75011 Paris
France
Tel. +33 1 53 86 87 50
Fax +33 1 47 34 56 72
E-mail: info@lucanepharma.com

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.