Friday, February 20, 2015

Delamanid: A few words


Tuberculosis is a topic that I have talked about a longtime ago. It a topic that is very hard to be kept track of. With an encouraging drug approval in the TB pipeline, after a staggering 40 years, there is a sudden increase in interest in new drugs and combination of drugs all aimed at reducing the current longterm treatment strategy.

In my earlier post, I talked about Anti TB drugs in some new combinations. In the post, I mentioned in passing a compound code named- OPC-67683. The compound was then under development by Otsuka Pharmaceutical Co. Ltd. The drug has now come sufficiently far in research to claim equivalence with drugs such as Bedaquiline. The drug is now known as Delamanid. The drug is a member of nitroimidazole class which attacks Mycolic acid synthesis pathway. The drug has received much attention after its approval from European medicines agency (EMA), Japan and Korea for the treatment of MDR-TB. Like other classic Anti- Mycobacterial's it is a prod drug. It is activated by the enzyme deazaflavin dependent nitroreductase. Currently it is seen as a strong candidate for Anti-TB and planned to be used in combination therapy. One of the strong contenders for combination is bedaquiline.

Fig 1: Structure of Delamanid. Source
With a huge interest of research in developing new Anti-TB drugs are making its appearance in clinical pipeline. As I have discussed previously (Link), the problem in treating TB is the period required to treat rather than the organism. Patients refuse to comply for a very long time. New set of drugs in pipeline are aggressive drugs and supposed to reduce treatment duration. However, all the new drugs are reserved for treating MDR TB. This because like any other drug, over use of this drug will lead to resistance and we will be back in square zero. This has led to some debates. On one hand you have a drug that can cure faster, thereby reducing the treatment time and thus avoiding emergence of resistance by eliminating problems with patient compliance. On the other there is a risk of resistance inducement owing to widespread use. I found some serious flaws in this arguments. The studies are showing that Anti TB drugs have better outcomes when given for 6 months in comparison with a 2 month regimen. So it is still a good idea to have them as drugs for MDR's which is difficult to otherwise treat.
Gruber K (2015). Access sought to tuberculosis drug from nutraceutical company. Nature medicine, 21 (2) PMID: 25642939

Xavier AS, & Lakshmanan M (2014). Delamanid: A new armor in combating drug-resistant tuberculosis. Journal of pharmacology & pharmacotherapeutics, 5 (3), 222-4 PMID: 25210407

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 (2012). Delamanid for multidrug-resistant pulmonary tuberculosis. The New England journal of medicine, 366 (23), 2151-60 PMID: 22670901

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