Otsuka Pharmaceutical Co., Ltd.

March 27, 2013

Otsuka's Novel Treatment for Multidrug-Resistant Tuberculosis, Delamanid,
Submitted For Regulatory Approval in Japan -- Half Century Since Last Drug Was Approved in Japan for Tuberculosis

  • Delamanid, discovered and developed by Otsuka, has been filed in Japan for the treatment of multidrug-resistant tuberculosis (MDR-TB), following the application in Europe in 2011. This is the first drug application in Japan seeking an indication for treatment of MDR-TB.
  • According to WHO, tuberculosis is one of the three most common infectious diseases. Every year, approximately 8.7 million people become sick, and nearly 1.4 million people die from TB or TB-related causes. It is estimated that 440,000 new cases of MDR-TB emerge each year, leading to 150,000 deaths annually.
  • Otsuka has been working in the TB field for more than 40 years and in 2011 was recognized as the world's lead investor in TB drug development.*i Otsuka is driven by the dream to create a novel drug for tuberculosis.

Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announced it filed an application with the Pharmaceutical and Medical Devices Agency in Japan (PMDA) to market its novel compound delamanid for the treatment of pulmonary multidrug-resistant tuberculosis (MDR-TB) in combination with an optimized background regimen (OBR) according to WHO and Ministry of Health, Labour and Welfare (MHLW) guidelines in adult patients. The MHLW has designated delamanid as an Orphan Drug.

The PMDA filing is based on the combined, published results of a robust phase 2 trial (trial 204) in 481 MDR-TB patients at 17 centres in nine countries, and two long-term extension trials (trials 208 and 116). In trial 204, delamanid plus OBR demonstrated a 53% increase in sputum culture conversion (SCC) at two-months, compared to 29.6% treated with placebo plus OBR alone. SCC is an indication of when a patient is no longer infectious. A combined analysis of results from trials 204, 208 and 116 found that 74.5% of patients treated with delamanid for six months experienced favorable outcomes, compared to 55% among those treated with delamanid or placebo for two months. A seven-fold reduction in mortality was also seen. Among patients with extensively drug-resistant tuberculosis (XDR-TB), higher rates of sustained conversion, a reduction in mortality, and improved final treatment outcomes were reported.

Delamanid was also well-tolerated among study subjects in the phase 2 trial, with a comparable adverse event profile across treatment groups. Study subjects receiving delamanid experienced a higher incidence of QT prolongation on electrocardiogram than those in the placebo group. These events were not associated with any clinical manifestations such as syncope or arrhythmias.

A global, randomized controlled six-month Phase 3 trial is currently enrolling patients to explore treatment with delamanid plus OBR in patients with MDR-TB, including those with co-existing HIV infection.

This is the second major regulatory filing for delamanid. A Marketing Authorization Application (MAA) is currently under review by the European Medicines Agency (EMA) and Otsuka also plans to submit delamanid for approval with the U.S. Food & Drug Administration.

Otsuka has been working the TB field for more than 40 years and has been a recognized leader in tuberculosis research through its commitment to the discovery and development of new tuberculosis compounds as well as the building of a clinical infrastructure within the developing countries affected by the disease.


Tuberculosis is a highly contagious airborne infection. Approximately one-third of the world's population is estimated to be infected with TB. According to the latest WHO Global Tuberculosis Control report, in 2011 approximately 8.7 million people became sick, and nearly 1.4 million people died from TB or TB-related causes.*ii Despite substantial efforts to control TB, the disease remains a significant public health burden; in the past two decades, this burden has increased with the rise of multidrug-resistant TB, or MDR-TB, a hard-to-treat form of the disease that is resistant to first-line therapies. This resistance emerges from the misuse of TB therapies, including poor drug supply, poor drug quality, or patients' inability to complete their treatment regimens. It is estimated that 440,000 new cases of MDR-TB emerge each year, leading to 150,000 annual deaths. Twenty-seven countries around the world account for 86% of the MDR-TB burden. *iii