For the first time in 40 years a new medicine for the treatment of MDR TB appeared

The emergence of drug resistance is a major threat to global tuberculosis (TB) care and control. The World Health Organization (WHO) estimates that up to half a million new cases of multidrug-resistant tuberculosis (MDR-TB) cases (i.e. resistant to, at least, rifampicin and isoniazid) occur each year globally. In Ukraine in 2013, there were about 9700 patients with MDR-TB (18.7% patients with MDR-TB among all newly diagnosed TB cases, 38.8% patients with MDR-TB among re-treatment cases according to statistics), among whom about 1 000 TB with extensively drug-resistant tuberculosis (XDR-TB), which is recognized as resistance to any fluoroquinolones and at least to one of three injectable second-line drugs (capreomycin, kanamycin and amikacin) in addition to the MDR-TB.  Current treatment regimens for MDR-TB are far from satisfactory: high cost of drugs, long-term overall treatment (duration is 20 months or more), necessity of taking of the drugs that are more toxic and less effective than those used to treat drug-susceptible TB. And as a result - low percentage of successful treatment.

Among MDR-TB patients started treatment in 2009 all over the world, only 48% were treated successfully (in Ukraine in 2009-2010 treatment efficiency was 27.5% and 29.3% accordingly). The mortality rate remains high among patients with XDR-TB: the global average of 2009 - 15%. In Ukraine, the mortality rate in 2009-2010 was 31.2% and 33.1% accordingly. Because of the increase of adverse reactions after taking the  drugs for the XDR-TB treatment and other factors, in 2009 28% of patients were lost to follow-up. In Ukraine in 2009-2010 this rate was 32% and 28.1% accordingly. In a subset of 200 extensively drug-resistant tuberculosis (XDR-TB) patients in 14 countries, treatment success reached only 33% overall and 26% of the patients died. New drugs that would help build a better, safer, less toxic, shorter and cheaper regimen are therefore urgently needed to reduce patient suffering and mortality.

The landscape of TB drug development has evolved dramatically over the past ten years New drugs for the treatment of MDR-TB are entering to Phase III of clinical trials. Among these, a new drug, bedaquiline, has recently (December 2012) been granted accelerated approval by the United States Food and Drug Administration (US-FDA) based on Phase IIb of clinical trials. Similar submissions are currently being made to other national regulatory authorities worldwide. Bedaquiline is already used in several countries in Europe, Asia, USA and Russia.

In 2013, the World Health Organization (WHO) has published interim guidelines for Bedaquiline use in the treatment of MDR-TB for adults.

Particularly high hopes for a new and effective drug have countries with a high burden of MDR TB, including Ukraine. This drug could be one of the key factors to overcome the growing threat of MR-TB epidemic.

It should be emphasized that the development and implementation of new drugs in the TB treatment is one of the five priority development areas for acceleration of goals achievement by 2015 according to the WHO recommendations.

Bedaquiline (Syrturo, TMC207) - TB drug with a new mechanism of action that affects the livelihoods of Mycobacterium tuberculosis (Mycobacterium tuberculosis) by inhibiting ATP synthase - an enzyme that is necessary for the  bacteria’s cell energy supply. Inhibition of ATP synthesis leads to loss of Mycobacterium tuberculosis in humans.

Bedaquiline can be assigned to adult patients with MDR-TB, along with other treatment recommended by WHO under the following conditions:

• in case of inability to prescript effective treatment regimens that according to WHO recommendations contains four second-line drugs and pyrazinamide;
• in case  if there is documentary evidence of multiple drug resistance and resistance to any drug fluoroquinolones group.

According to results of clinical trials, the percentage of cured patients with a diagnosis of MDR TR, which received in the treatment regimen Bedaquiline, is 57.6% and in the placebo group - 31.8%. Below are summarized  evidences of Bedaquilineu efficiency in treatment of patients with MDR-TB, negative results of AFS microscope  (conversion of Culture) is taken as a basis.

Summary of evidence for the efficacy of Bedaquiline in the treatment of MDR-TB

This drug has passed the second of 4 phases of clinical trials, which entitles the manufacturer to register it at government authorities for use in the treatment of patients with MDR TB.

The situation in Uk raine with bedaquiline comments manager of the Program « Stop TB in Ukraine» Inna Motrych, MD. «In Ukraine bedaquiline is still not registered, because according to Ukrainian legislation drug should be submitted to the registration by the natural or legal entity responsible for the supply of the drug. Registration of the drug is associated with additional costs for the supplier for inclusion in the state register of medicinal products and expert report of State Scientific Advisory Centre of drugs (Ministry of Health). Due to the small number of patients who need this drug, importing this drug is not profitable for the supplier. In view of the above its a vicious circle, on the one hand, the state cannot conduct procurement of an unregistered drug, and on the other provider does not register a new drug due to lack of financial interest. To purchase bedaquiline for state funds there is another obstacle - it is necessary to submit it to drug nomenclature list. New drug is very difficult to add to the list of nomenclature, due to the fact that the state will need to purchase them, but the state as usual have a shortage of money. Cost of bedaquiline treatment (8 months) is almost 40 000 UAH ($ 3000) – the price of Global Medicinal Fund.

There is another possible way of importation of the drug - based on the individual decision of Ministry of Health (Article 17, part 6, Law on medicines) on the import of unregistered drug due to epidemic diseases, which includes tuberculosis.

Patients with XDR-TB had the opportunity to get bedaquiline for the Global Fund costs, but the working group has decided to give 70% of funds to fight HIV infection and only 30% left for TB activities. This small sum is not enough to purchase bedaquiline.

In view of the above, patients with the most severe form of TB (XDR-TB) in 2014 left without a chance to get the modern treatment with bedaquiline.»