June 6 (Reuters Health) - Researchers who tested a novel type of antibiotic against multi-drug-resistant tuberculosis are reporting that nearly half of patients who were given the new drug cleared the bacteria from their lung fluid in two months.
The multinational clinical trial of experimental drug delamanid found that volunteers who received it, along with a standard regimen of other anti-TB medicines, were far more likely to see the bacteria disappear from their sputum than those who got just the older medicines.
That “conversion” of sputum cultures happened much more quickly in patients taking the new drug, according to Lawrence Geiter, a vice president at Otsuka Pharmaceutical Co, which developed delamanid, and an author of the study.
Otsuka also designed and financed the clinical trial, which took place in 17 medical centers across nine countries.
“We saw what we think is a reasonable safety profile,” Geiter told Reuters Health in a telephone interview. “(So) this could be the first new class of TB compounds that would be licensed in nearly a half century.”
The results, published in the New England Journal of Medicine, are being called “significant but modest” in an accompanying editorial by Drs. Richard Chaisson and Eric Nuermberger of the Johns Hopkins University School of Medicine in Baltimore.
“We’ve been looking for new chemical classes of drugs for tuberculosis for a while,” said Scott G. Franzblau, director of the Institute for Tuberculosis Research at the University of Illinois at Chicago, who was not connected with the study.
He told Reuters Health it is not surprising that a new drug would help against drug-resistant strains.
“That’s kind of a given. Any new class of TB drug is expected to work against drug resistant strains because they haven’t had a chance to become resistant to it. That’s the easier part in making a dent in TB,” he said.
“The harder part is, can you really get a drug that will help you shorten treatment? The preclinical data in mice suggested that this drug should be able to do that as well as others in its class, one of which is in clinical trial and the other is in a preclinical trial.”
Tuberculosis causes about 1.8 million deaths each year and about 440,000 cases worldwide involve bacteria that have learned to resist conventional drugs such as isoniazid and rifampin.
Patients with multi-drug-resistant TB have to take four to six expensive medications, some with significant side effects, for as long as two years at a cost of up to $5,000.
All of the 481 TB patients in the new study received conventional treatment with a drug combination developed by the World Health Organization.
Of the 161 who were also given 100 mg of delamanid twice daily, 45.4 percent had no trace of the TB bacterium in their lung fluid after two months. With a twice-daily dose of 200 mg, given to 160 people, the rate was 41.9 percent. That compares with 29.6 percent among the 160 volunteers given a placebo along with conventional treatment.
Headache, insomnia and upper abdominal pain affected at least one in five patients getting delamanid. Nausea and vomiting were reported by about a third. But the rate of both side effects was not significantly higher than among those receiving placebo.
A more serious concern was the risk of a heart abnormality known as a prolonged QT interval, which stretches out the period between heartbeats.
The researchers found that 13 percent of the patients getting the highest dose of delamanid had a prolonged QT interval, as did 10 percent on the lower dose - compared with just 3.8 percent in the placebo group.
The problem occurs at the point “when the heart is repolarizing and charging the battery to do the next beat,” Geiter said.
“If the interval gets really long, much longer than we observed, it’s not able to beat again in a functional manner so you start to get fibrillations or arrhythmias,” which affect the flow of blood and can cause fainting.
None of the patients had any heart symptoms, however.
“This is something we’ll continue to look at,” Geiter said.
A longer study that will examine the effect of six months of treatment with delamanid, and follow those patients for 30 months, is underway. SOURCE:New England Journal of Medicine, online June 6, 2012.