New tuberculosis drugs approved by European Medicines Agency
The European Medicines Agency has recommended marketing authorisations for three new drugs used for the treatment of multidrug-resistant tuberculosis.
At the end of 2013, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended granting conditional marketing authorisations1 for delamanid (Deltyba) and bedaquiline (Sirturo), and recommended granting a marketing authorisation for Para-aminosalicylic acid Lucane (para-aminosalicylic acid), for use in combination with other medicines against multidrug-resistant tuberculosis. The three marketing authorisations are all pending decisions by the European Commission.
Delamanid received a positive opinion for the conditional marketing authorisation for the treatment of adult patients with pulmonary infections due to multidrug-resistant tuberculosis when an effective treatment regimen cannot otherwise be devised for reasons of resistance or tolerability (2). It exerts its activity by inhibiting the synthesis of the mycobacterial cell wall components, methoxy-mycolic and keto-mycolic acid.
The authorisation was based on one main study involving 481 patients with pulmonary multidrug-resistant tuberculosis (3). Patients in the study were given delamanid or placebo for two months in combination with a background drug regimen developed according to World Health Organization guidelines. Among patients who received a background drug regimen plus delamanid, 44% had sputum-culture conversion at 2 months, as compared with 30% of patients who received a background drug regimen plus placebo. Most adverse events were mild to moderate in severity and were evenly distributed across groups. QT prolongation was significantly more frequently in the groups that received delamanid.
The CHMP took the view that although it cannot be assumed that the study results showing effectiveness at two months automatically predict effectiveness at six months (intended duration of prescription), this was considered likely. In addition, an on-going clinical study will examine responses at six months and should provide confirmation of the long-term effectiveness and safety. The CHMP recommended that an additional study should be carried out to confirm that the current recommended dose is the most appropriate dose. A pharmacovigilance plan for delamanid will be implemented as part of the marketing authorisation.
Para-aminosalicylic acid Lucane
The positive opinion for the marketing authorisation for Para-aminosalicylic acid Lucane is for the treatment of multidrug-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. Para-aminosalicylic acid Lucane is a new formulation of para-aminosalicylic acid.
In December 2013, the CHMP recommended the granting of a conditional marketing authorisation for the medicinal product bedaquiline for the same indication as delamanid. Bedaquiline was approved by the U.S. Food and Drug Administration in December 2012.
The studies presented to the CHMP showed bedaquiline to be efficacious in terms of sputum culture conversion. They also seem to indicate that bedaquiline currently does not show cross-resistance to any available tuberculosis medicines.
The marketing authorisation is conditional because additional studies are required to further define the optimal use of the agent, both with regards the number and types of agents that are needed in combination, and the optimal treatment duration. Also a pharmacovigilance plan for bedaquiline will be implemented as part of the marketing authorisation.
Multi-drug resistant tuberculosis in the European Union
Of the 72,334 tuberculosis cases notified in the European Union and European Economic Area in 2011, 1,522 were known to be resistant to rifampicin and isoniazid and were thus classified as multi-drug resistant tuberculosis3. Of the total number of multi-drug resistant tuberculosis patients notified in 2009, only 32% were successfully treated. The availability of new drugs for treatment of multi-drug resistant tuberculosis can help in reaching better treatment results.
Activities related to the introduction of new tuberculosis drugs
The World Health Organization has published an interim policy guidance that provides advice on the inclusion of bedaquiline in the combination therapy of multidrug-resistant tuberculosis in accordance with the existing WHO Guidelines for the Programmatic Management of Drug-resistant TB.
The European Centre for Disease Prevention and Control plans to conduct stakeholder and expert consultations and develop a guidance document to assist Member States with the introduction of new tuberculosis drugs.
- A conditional marketing authorisation is granted to a medicinal product that fulfils an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. The marketing authorisation holder should carry out the additional studies to find out more about the medicine’s benefits and safety in the long term.
- Gler MT, Skripconoka V, Sanchez-Garavito E, Xiao H, Cabrera-Rivero JL, Vargas-Vasquez DE, Gao M, Awad M, Park SK, Shim TS, Suh GY, Danilovits M, Ogata H, Kurve A, Chang J, Suzuki K, Tupasi T, Koh WJ, Seaworth B, Geiter LJ, Wells CD. Delamanid for multidrug-resistant pulmonary tuberculosis. N Engl J Med. 2012 Jun 7;366(23):2151-60. doi: 10.1056/NEJMoa1112433.
- European Centre for Disease Prevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2013. Stockholm: European Centre for Disease Prevention and Control, 2013.
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