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Delamanid – Use, dose, trials, side effects & availability

Delamanid is the active substance in a new TB drug treatment.  Delamanid (formerly called OPC-67683) is also known by its trade name of Deltyba. It is the first in a new class of TB drugs called nitroimidazoles. It is currently being developed by the Otsuka pharmaceutical company as a treatment for MDR TB.

Use

Delamanid for the treatment of MDR-TB

Delamanid for the treatment of MDR-TB

Delamanid is given to adults with TB that is affecting the lungs, and which is multi drug resistant (MDR). This means that it is resistant to at least isoniazid and rifampicin, two standard anti-tb drugs. It is used together with other standard medicines, and it must not be taken on its own. It is used when other drug combinations cannot be used either because the TB bacteria are resistant to the other drugs or because of the side effects of these other drugs.

Dose

It is available as 50mg tablets and the recommended dose is two tablets taken twice a day with food.1“Deltyba delamanid Summary of the European public assessment report (EPAR) for Deltyba”, European Medicines Agency 2013 www.ema.europa.eu It needs to be taken for six months.

Delamanid clinical trials

The main results of clinical trials come from a phase IIB trial together with studies of safety and efficacy.

Phase IIB trial

In July 2012 the results of a phase 2B trial showed delamanid plus a background regimen resulted in more study subjects becoming non-infectious after two months than a placebo plus a background regimen. The trial was conducted in 17 centres in nine countries.2“The New England Journal of Medicine Publishes Efficacy Results of Otsuka’s Delamanid for Multidrug-Resistant Tuberculosis”, Business Wire, www.businesswire.com/news/home/20120606005698/en/England-Journal-Medicine-Publishes-Efficacy-Results-Otsukas

Among patients who received a background regimen plus 100 mg twice daily, 45.4% had culture conversion at two months as compared with 29.6% of patients who received background plus placebo.

Patients who took part in two earlier studies were also then able to take part in a 24 month observational study designed to look at treatment outcomes. This observational study found that favourable outcomes were observed in about three quarters of the patients who received delamanid for more than six months. This compared to about half of the patients who received delamanid for less than two months.

The Otsuka company has also started a phase three trial of Delamanid. The trial which started in September 2011, is designed to show if delamanid is both safe and effective when given as TB drug treatment over a six month period. The completion date for the first tests of effectiveness was August 2013.

Delamanid for the treatment of XDR TB

In July 2015 data was published on the effectiveness of delamanid  for the treatment of XDR TB. This was a further analysis of the earlier phase IIB study. XDR TB is defined by the World Health Organisation as strains of TB that are resistant to the drugs isoniazid and rifampicin. They must also be resistant to at least one drug in the fluoroquinolone group as well as another second line injectable drug.

Patients with XDR-TB who received delamanid in addition to a WHO recommended optimised background regimen (OBR), had a higher proportion of patients who had culture conversion at 2 months. This was when compared with patients receiving placebo plus OBR alone. As a result the patients who took delamanid had a greater likelihood of a successful treatment outcome.

“XDR-TB is one of the deadliest and most difficult forms of TB to treat. More new medicines are urgently needed to prevent XDR-TB from becoming a death sentence. If confirmed, the analysis shows that delamanid may be an effective option to improve the current standard of care.”
Dr Andra Cirule, lead study investigator

The Side Effects of Delamanid

The most common side effects are nausea, vomiting and dizziness. These may affect as many as a third of all patients. There is also a serious side effect called QT prolongation. QT prolongation is an alteration of the electrical activity of the heart. It can cause a life-threatening abnormality of the heart rhythm. Anxiety, pins & needles, and shaking are other important side effects.3“Deltyba delamanid Summary of the European public assessment report (EPAR) for Deltyba”, European Medicines Agency 2013 www.ema.europa.eu

Regulatory Approval

In April 2014 delamanid received “conditional approval” by the European Medicines Agency (EMA).4“Deltyba delamanid Summary of the European public assessment report (EPAR) for Deltyba”, European Medicines Agency 2013 www.ema.europa.eu This means that more evidence needed about the drug, and Otsuka is required to provide this. The company that markets Deltyba is to carry out further studies to confirm the long term effectiveness and safety of Deltyba.

In July 2014 delamanid was also approved by the Japanese regulatory authority.

In October 2014 the World Health Organisation (WHO) released its interim policy guidance for the use of the drug in the treatment of MDR-TB.

FighTBack Initiative

Otsuka, the manufacturer of has announced a “FighTBack Initiative”. This is a plan to provide delamanid for 20% of all diagnosed and treated MDR-TB patients, in quality management programmes by 2020.

Availability of delamanid

But there have been calls for Otsuka in practice to make delamanid more quickly widely available.

“The global TB community must rally together to ensure delamanid is widely and quickly accessible to those in need. This will involve coordinated efforts to ensure health systems have safeguards in place to ensure rational use and monitoring of delamanid. It will also require global coordination to ensure reliable, uninterrupted supplies of delamanid are provided at affordable prices.”
Dr Lucica Ditiu, Executive Director, Stop TB Partnership5“New Data on Delamanid Shows Promising Effects on XDR-TB Treatment”, Stop TB Partnership, http://www.stoptbb.org/news/stories/2015/ns15_032.asp

Global use

As part of efforts to improve treatment outcomes for MDR/XDR-TB, at least 39 countries had started using delamanid by the end of 2015. But by October 2016 only 405 patients had received delamanid.6“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

You can read more about:

Bedaquiline

Multi drug resistant TB

TB in India

References

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1. “Deltyba delamanid Summary of the European public assessment report (EPAR) for Deltyba”, European Medicines Agency 2013 www.ema.europa.eu
2. “The New England Journal of Medicine Publishes Efficacy Results of Otsuka’s Delamanid for Multidrug-Resistant Tuberculosis”, Business Wire, www.businesswire.com/news/home/20120606005698/en/England-Journal-Medicine-Publishes-Efficacy-Results-Otsukas
3. “Deltyba delamanid Summary of the European public assessment report (EPAR) for Deltyba”, European Medicines Agency 2013 www.ema.europa.eu
4. “Deltyba delamanid Summary of the European public assessment report (EPAR) for Deltyba”, European Medicines Agency 2013 www.ema.europa.eu
5. “New Data on Delamanid Shows Promising Effects on XDR-TB Treatment”, Stop TB Partnership, http://www.stoptbb.org/news/stories/2015/ns15_032.asp
6. “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