Otsuka Holdings Co. (4578)’s experimental tuberculosis drug was effective against patients with infections resistant to older medications in a study, findings that may lead to the first new TB treatment in 40 years.
Patients with pulmonary multidrug resistant TB, or MDR-TB, were given Otsuka’s delamanid or a placebo twice daily for the first two months of treatment in combination with older drugs. At least 42 percent of those taking delamanid didn’t have the bacteria in mucous from the lungs compared with 29.6 percent for those who took placebo, according to a company-funded trial published today in the New England Journal of Medicine.
Tuberculosis caused 1.4 million deaths worldwide in 2010, making it the second-greatest infectious disease killer after HIV, according to the World Health Organization. If successful, Otsuka’s treatment may help control the growing threat of drug- resistant infections. About 650,000 cases of MDR-TB were reported globally in 2010, with about 150,000 dying from the infection, the Geneva-based agency said.
“I’m very excited,” Manfred Danilovits, a doctor at Tartu University Hospital in Estonia and the principal investigator of the study, said in a telephone interview. “It showed quite good effectiveness, it reduced infectiousness, meaning they won’t spread the disease to other people anymore.”
The trial involved 481 patients at 17 centers in nine countries ages 18 to 64 who had tested positive for multidrug- resistant TB. Patients either took 100 milligrams or 200 milligrams of delamanid or a placebo twice daily for two months, with a background drug regimen developed according to the WHO guidelines.
Most of the side effects were mild to moderate and evenly distributed across groups, though, irregular heartbeat reported to be significantly more frequent in groups taking delamanid, the study said.
“Generally, it seems to be a safe drug,” Danilovits said. The increase in irregular heartbeat needs to be studied more, he said.
Otsuka, based in Tokyo, filed for regulatory review of the medicine in Europe in December and is negotiating with Japanese and American authorities on terms for the filings, said Masuhiro Yoshitake, head of the global TB projects at Otsuka’s drug unit in an interview on June 5.
TB is a contagious bacterial infection and usually treated with a regimen of drugs taken for six months to two years, according to the National Institute of Allergy and Infectious Diseases. Symptoms include weight loss, fever and loss of appetite and infected patients can develop coughs, chest pain and bloody mucous coughed up from the lungs.
TB became possible to cure in the mid-1940s with the discovery of the antibiotic streptomycin. Almost all the drugs used to fight it were found in the next two decades. Their effectiveness has been hampered by HIV. TB can flourish in HIV sufferers because the AIDS-causing virus attacks T-cells, the body’s immune defenders crucial in keeping tuberculosis at bay.
MDR-TB is a form of drug-resistant TB in which the bacteria can’t be killed by at least the two antibiotics isoniazid and rifampin, the most powerful standard treatments, according to the WHO. It’s curable by using second-line drugs, though options are limited, can be costly and cause severe side effects, the agency said.
At least two other experimental medicines to fight TB are in development. Bedaquiline from New Brunswick, New Jersey-based Johnson & Johnson (JNJ) and PA-824, which a company now owned by Swiss drugmaker Novartis AG (NOVN) licensed to the TB Alliance, a New York- based nonprofit group supported by the Gates and Rockefeller Foundations, are in the second stage of three trials generally required for regulatory approval.
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