Otsuka Pharmaceutical Co., Ltd.

July 16, 2015

Efficacy Results of Otsuka's Delamanid (Deltyba) for Extensively Drug-Resistant Tuberculosis (XDR-TB) Published in the New England Journal of Medicine

  • Analysis of data from Phase IIb trial showed that delamanid plus a background regimen appeared to be a promising treatment option in complex, difficult-to-treat XDR-TB patients.
  • Delamanid plus a background treatment regimen rendered more patients non-infectious after two months compared to placebo plus a background treatment regimen.
  • By 2014, 100 countries, including the U.S., reported at least one case of XDR-TB, which the WHO defines as resistance to first-line drugs isoniazid and rifampicin, as well as resistance to at least one fluoroquinolone and another second-line injectable.

Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announced that data from a post-hoc subset analysis of its Phase IIb clinical trials suggesting potential efficacy of delamanid for the treatment of extensively drug-resistant tuberculosis (XDR-TB) was reported in this week's New England Journal of Medicine. The analysis found that patients receiving delamanid, plus a World Health Organization (WHO)- recommended optimized background regimen (OBR), had a higher proportion of 2-month sputum culture conversion (SCC), a measurement by which patients are no longer infectious, compared to patients receiving placebo plus OBR alone (7/16, 43.8% vs. 1/10, 10%, p=0.0989). In this same open-label analysis, mortality trended lower when patients received six months or more of delamanid compared to patients treated for two months or less (0/17, 0% vs. 2/9, 22.2%, p=0.11).

"XDR-TB is one of the most deadly and difficult forms of TB to treat," said Dr. Andra Cirule, one of the lead study investigators and a tuberculosis specialist at Riga East University Hospital in Latvia. "More new medicines are urgently needed to prevent XDR-TB from becoming a death sentence and this analysis shows that delamanid may be an effective option to improve the current standard of care."

XDR-TB develops from misuse or mismanagement of second-line TB therapies, which severely limits treatment options. 100 countries have reported at least one case of this dangerous strain, including the U.S., where contract tracing is currently ongoing after an infected patient exposed individuals in at least three states to the disease.

"The study's important findings reaffirm Otsuka's commitment to continued research on this major global health threat," said Masuhiro Yoshitake, executive operating officer of Otsuka and TB Global Project leader. "For over 40 years, Otsuka has made it a priority to identify new treatment options for even the most challenging TB cases, and we look forward to continued progress against this deadly strain."

Delamanid is the first compound from a novel drug class (nitro-dihydro-imidazooxazoles) that is bactericidal and specific to Mycobacterium tuberculosis, including multidrug-resistant (MDR-TB) strains. It has received regulatory approval in the European Union, Japan and the Republic of Korea. In October 2014, the WHO released its interim policy guidance for the use of delamanid in the treatment of MDR-TB and in May 2015, the WHO added delamanid to its Essential Medicines List, which includes medicines based on the scientific evidence of their comparative effectiveness, safety, and cost-effectiveness.

More About This Study

The efficacy of delamanid was studied in a large, randomized, placebo-controlled phase 2 trial that included a 2-month treatment period and a 1-month follow-up of 481 MDR-TB patients (Trial 204), with 213 patients continuing to a 6-month open-label treatment trial (Trial 208), and concluding with a 24-month follow-up study of 421 out of the originally randomized 481 patients (Trial 116). Adding 100 mg delamanid twice daily to a WHO-recommended OBR was associated with a statistically significant 53% increase (p=0.008) in the percentage of patients achieving SCC at 2 months (45.4%) compared with those with added placebo (29.6%).
Clinical trial results demonstrated that adverse events were evenly distributed in the delamanid and placebo treatment groups with the exception of QT prolongation. Electrocardiogram QT prolongation was reported in 9.9% of patients receiving delamanid as 100 mg twice daily compared to 3.8% of patients receiving placebo plus OBR. This was not accompanied by any clinical symptoms such as syncope or arrhythmias.

About TB

According to the WHO, tuberculosis is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent. In 2013, an estimated 9 million people became sick with TB, and 1.5 million people died from TB or TB-related causes. Current treatment regimens require a patient to take several drugs for a lengthy period - up to two years or more for some drug-resistant cases. Approximately 480,000 people developed MDR-TB in 2013.