Bedaquiline - use, potential problems, South Africa & India

What is bedaquiline?

Bedaquiline is the active substance in a new TB drug which is also sometimes known by the trade name of Sirturo. It belongs to a group of drugs known as diarrylquinolines. It is the first new TB drug for 40 years. There is more about the history of TB drugs.

How does it work?

Bedaquiline a new drug for the treatment of tuberculosis

Bedaquiline a new drug for the treatment of tuberculosis

Bedaquiline works by blocking an enzyme inside the bacteria that cause TB. Enzymes are molecules which speed up chemical reactions in the body. The particular enzyme which is blocked is one that is used by the bacteria to generate energy. Without the ability to generate energy, the TB bacteria die and the patient’s condition should start to improve.1S Deoghare, "Bedaquiline: A new drug approved for treatment of multidrug-resistant tuberculosis", Indian Journal of Pharmacology, 2013, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793534/

When is bedaquiline used?

Bedaquiline should only be used in combination with other TB drugs to treat pulmonary TB in adults when they have multi drug resistant TB (MDR-TB). MDR-TB is when the TB bacteria that a person is infected with, are resistant to two of the main TB drugs isoniazid (INH) and rifampicin (RMP). This means that the drugs don’t work

It is essential that it is only used when effective TB treatment cannot otherwise be provided. It is usually used when other drugs cannot be used because of their side effects or when a person has bacteria that are resistant to other drugs, which means that the drugs won't work.

It should also always be used in combination with at least 3 other TB drugs which drug susceptibility testing has shown that the patient is susceptible to. If drug susceptibility testing is not available then bedaquiline should be used with at least 4 other drugs to which the patient is likely to be susceptible.

If a TB patient is to take bedaquiline, then this must always be done under the supervision of an experienced doctor.

What are the potential problems with the misuse of bedaquiline

If a new drug is inappropriately used, for example if bedaquiline was to be used with just one other drug, then it is possible that the TB patient (or to be technically correct their bacteria) could develop drug resistance. That drug resistant form could then be passed on to other patients, for whom bedaquiline would no longer be effective.

So in order to ensure that as many people as possible benefit from bedaquiline and other new TB drugs, it is essential that the use of new TB drugs is carefully controlled. So bedaquiline must be only prescribed and taken by patients in accordance with World Health Organisation and National Treatment Program guidelines.2"Antimicrobial resistance", World Health Organisation, https://www.who.int/topics/antimicrobial_resistance/en/

When did bedaquiline first become available?

New drugs become available in different countries at different times.

In the United States the US Food and Drug Administration (FDA)  granted approval on 28th December 2012 for bedaquiline to be used to treat drug resistant TB.3FDA News Release, 31st December 2012 www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/

In October 2013 the CDC issued new federal guidelines on the use of the drug, for the treatment of multi drug resistant TB.4“Provisional CDC Guidelines for the Use and Safety Monitoring of Bedaquiline Fumarate (Sirturo) for the Treatment of Multidrug-Resistant Tuberculosis”, CDC October 2013 www.cdc.gov/mmwr/preview/mmwrhtml

The new guidelines offered advice on the use of the drug for the treatment of TB in children, pregnant women and individuals with other health complications.

In June 2013 the World Health Organisation issued interim guidance on the inclusion of bedaquiline in combination drug therapy for people with MDR TB.5“Janssen-Cilag files for EU approval of bedaquiline in MDR-TB”, The Pharma Letter,
www.thepharmaletter.com/file/116136/janssen-cilag-files-for-eu-approval-of-bedaquiline-in-mdr-tb

Worldwide approval

By 2015 the drug had received approval for use in the United States, the EU, South Korea, South Africa, India, the Russian Federation and Peru.6“First time in decades: New antibiotic to treat Multidrug-Resistant Tuberculosis (MDR-TB) receives approval in Peru”, Stop TB Partnership, 2015, www.stoptb.org/news/frompartners/2015/fp15_012.asp However, by October 2016 only 5,700 patients had been able to receive the drug.7“Access: MSF reports on use of the new tuberculosis drugs bedaquiline and delamanid”, MSF,
http://www.msf.org/en/article/access-msf-reports-use-new-tuberculosis-drugs-bedaquiline-and-delamanid

The cost of bedaquiline

In most low and middle income countries the aim is to provide TB diagnosis and treatment free of charge within public health services. 8"Financial burden for tuberculosis patients in low and middle income countries: a systematic review, 2014, European Respiratory Journal 2014, https://erj.ersjournals.com/content/43/6/1763 But a patient will usually have to pay the cost of getting to the health centre. With a new drug this may often be some distance from where a patient lives. A patient may also need to pay for any tests required to find out if the TB treatment has been successful.9"Personal communication" There is more about the cost of TB treatment.

The donation program involves the company Janssen providing free bedaquiline to be used in low and middle income countries. The program was set up in March 2015 when USAID and the company Janssen Therapeutics signed an agreement to provide the drug free to eligible MDR-TB patients. Under the agreement Janssen would donate $30 million worth (30,000 treatment courses) of the drug over a four year period to be used for the treatment of drug resistant TB. It was said at the time that this would enable over 100 low and middle income countries to have the drug available for free within their existing national MDR-TB programs.10“The Bedaquiline Donation Program”, Stop TB Partnership, 2015, www.stoptb.org/gdf/drugsupply/bedaquilineDonation.asp

Bedaquiline cost in high income countries

For high income countries the situation is very different, with bedaquiline costing US$30,000 in the United States. This is equivalent to £18,800 in the UK.11Wolfson, L “Cost-effectiveness of Adding Bedaquiline to Drug Regimens for the Treatment of Multidrug-Resistant Tuberculosis in the UK”, PLoS One 2015, www.ncbi.nlm.nih.gov/pubmed/25794045

Bedaquiline use in South Africa

In December 2012 the South African Medicine Control Council (MCC) approved a national program to treat selected drug resistant TB patients with bedaquiline. This program began in March 2013. The program operated at five South African sites and was subsequently extended to twelve sites. In October 2014 the MCC approved the use of bedaquiline within the national TB programme12“Good outcomes within the National Bedaquiline Clinical Access programme in South Africa”, HIV treatment bulletin, January 2015, http://i-base.info/htb/27735

By 2017 about two thirds of patients taking bedaquiline were in South Africa. Of the approximately 11,000 patients being treated for drug resistant TB, about 7,000 are now being treated with the drug.

In South Africa patients with XDR-TB are now automatically given bedaquiline as soon as they start treatment. MDR-TB patients only have access to the medicine if doctors find out that their drug regimen is causing serious side-effects.13“The fightback against tuberculosis starts now”, Health-e News, 18 June 2018,
https://www.dailymaverick.co.za/article/2018-06-18-the-fightback-against-tuberculosis-starts-now/#.Wyd1nKknZBw

In July 2018 the South African minister of Health, Dr Aaron Motsoaledi announced that the government of South Africa and Janssen, the manufacturer, had agreed a lower price of US$400 (from US$750) for a six month course of Bedaquiline.14“South Africa announces lower price for TB drug bedaquiline”, 2018, The Union, https://www.theunion.org/news-centre/news/south-africa-announces-lower-price-for-tb-drug-bedaquiline

Bedaquiline availability in India

In February 2016 it was announced that bedaquiline is to be made available in India.15“India set to roll out bedaquiline to combat extensively drug-resistant TB”, The Pharma Letter,
www.thepharmaletter.com/article/india-set-to-roll-out-bedaquiline-to-combat-extensively-drug-resistant-tb
The drug will be available as part of second line treatment for patients suffering from MDR-TB and XDR-TB. The drug recently underwent clinical trials at the national level in certain hospitals for safety and efficacy. There is more about the treatment of drug resistant TB in India.

Bedaquiline is a promising new TB drug but it must be carefully introduced and monitored. I have already seen media reports from India which call bedaquiline a ‘miracle drug’. This worries me – terms like ‘miracle drug’ should not be used lightly as it can raise expectations and also encourage abuse. More evidence is needed on how bedaquiline fits in with existing and other new drug regimens. It is not intended to be used alone”

Dr Madhukar Pai, Director of McGill Global Health Programme Canada16Mascarenhes, Anuradha,”The roll out of a TB curing miracle drug bedaquiline”, The Indian Express, March 2016,
http://indianexpress.com/article/explained/tuberculosis-bedaquiline-new-medicine-for-tb-cure/

There is also an issue about the private sector in India. More than half the TB patients in India seek care in the private sector. There is concern about whether the Indian government is engaging sufficiently with private health care providers about the use of the drug.

Janssen, the Belgain pharamaceutical company that manufactures bedaquiline, had a Compassionate Use Program between 2013 and 2016. This was previously used by the Hinduja Hospital in Mumbai to obtain bedaquiline for its patients with MDR TB. The hospital has prescribed the drug to 40 patients, with a 70% success rate.

Now that the drug is available from the RNTCP the compassionate use program has ended. However, the RNTCP has what is considered by some people to be a restrictive policy on the use of bedaquiline because of the fear of resistance developing. The team at Hinduja hospital is buying the drug for individual patients through the South African distribution branch. Dr Zarir Udwadia at Hinduja hospital believes that the drug should be made available to many more patients.17Shelar, Jyoti,”To save lives, hospital to import anti-TB drug from South Africa”, The Hindu, April 13, 2018,
www.thehindu.co-import-anti-tb-drug-from-south-africa/

By the end of 2019 the Indian government had rolled out the new oral regimens including Bedaquiline across seven states. The estimate is that the regimes will be rolled out nationally in the first quarter of 2020.18Maitri Porecha, Come 2023, generic companies will be able to manufacture anti-tuberculosis drug Bedaquiline, 2019, https://www.thehindubusinessline.com/companies/come-2023-generic-companies-will-be-able-to-manufacture-anti-tuberculosis-drug-bedaquiline-jansssen-india-managing-director/article29899749.ece#

In 2023, generic companies in India will be able to manufacture Bedaquiline.

Page Updating

This page was last updated in January 2020.

Photo copyright Getty Images/Science Photo Library RF/Creator Molekuul/Science Photo Library
Author Annabel Kanabus

Social Media

If you have found this page useful please tell other people about TBFacts.org and if you have a website please link to us at tbfacts.org/bedaquiline/

Would you like to send us a comment about this page?

You might like to read more about: