TB drug trial yields gains in drug-resistant disease treatment

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A study following patients who had  participated in a trial of a potential new treatment for drug-resistant tuberculosis has shown heartening results, with nearly three-quarters of patients who took the medicine for six months or longer showing “favorable outcomes”  — cured  or completed treatment —  according to a study published in the European Respiratory Journal.

Of 481 original trial participants, 421 — 87 percent — were followed for the study of Otsuka pharmaceutical company’s delamanid compound. Of 192 patients who received delamanid for 6 months or more, 143 showed favorable outcomes. Of 229 patients who took delamanid for two months or less, 126 — just 55 percent — showed favorable outcomes. Of the patients taking delamanid for six months or more, two died –one percent of those patients. This relatively low mortality rate, for patients with multidrug-resistant, and extensively drug-resistant tuberculosis was significant, and contrasted with 19 deaths — 8 percent — among the patients who took the drug for a shorter term. In the long term group, no one with extensively drug resistant tuberculosis died, while in the short term group, three of the patients who died were sick with extensively drug resistant tuberculosis.

While researchers at Otsuka were optimistic following the original trial results, the results of the followup study  exceeded expectations,  Lawrence Geiter, a vice president of Otsuka told Science Speaks.

“I was pleased,” he said. “To give you a feel for that survival number, mortality rate is usually in the range of 10-to-15 percent. One percent is definitely statistically significant.”

No new treatment of tuberculosis has been introduced in nearly half a century, while the development of strains of disease increasingly resistant to existing therapies has grown into a major global public health crisis. With treatment to combat these strains lengthy, toxic, expensive, and formidably difficult for patients — particularly those living in poverty — to maintain, the search for new treatment has gained impetus in recent years.

Otsuka became the first drug maker in nearly half a century to submit a new tuberculosis medicine to a regulatory authority when it filed with the European Medicines Agency in 2011, seeking approval for the medicine to be used to treat drug-resistant tuberculosis.  It could be approved by the middle of the next year, Geiter said. Another drug maker, Janssen-Cilag International, has since filed with both the EMA and the U.S. Food and Drug Administration, for approval for another new tuberculosis treatment, bedaquiline.

Bedaquiline has been made available for “compassionate use” — a conditional program in which a drug still under investigation is made available to patients with whom other treatment has been unsuccessful — in several European countries, and advocates have petitioned to have it accepted for use under that status in South Africa, which is home to one of the highest rates of multidrug-resistant tuberculosis in the world.

Delamanid has not been made available for compassionate use, but, Geiter said, Otsuka has been in discussions with organizations and agencies, including national tuberculosis control programs, that would be responsible for administering the drug under a compassionate use program. The company’s concern, he said, is that the drug be administered in a setting that would allow for directly observed therapy. Directly observed therapy, known as DOTS, is the World Health Organization standard for tuberculosis treatment, in which medicine is administered by, and taken in the presence of a healthcare worker or community care worker, to ensure that a treatment course is followed correctly.

“We need to ensure that delamanid not only gets to the patients who need it but that it is used appropriately, so we don’t generate resistance to it before it is even widely available,” he said. While the priority of pharmaceutical companies often is to generate rapid uptake of new medicines, he added, “That is not our motivation, at all.”

Making a drug available that will effectively address the epidemic that continues to evolve, is, he added.

“The development of drug resistance is a big threat for any drug introduced for treatment of tuberculosis.”



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