- Otsuka’s Deltyba is the first tuberculosis (TB) drug approval in Japan in over 40 years, and the only drug approval with an indication for MDR-TB.*1 Regulatory approval in Japan follows granting of a marketing authorization in Europe in April.
- The number of tuberculosis patients in Japan has declined year by year; however with an estimated 20,000 patients, the country still has one of the highest TB rates among highly developed countries.*2 The cure rate for MDR-TB has not improved over the past decade, complicating the elimination of TB in Japan. Declining efficacy of existing TB drugs has led to extended hospital stays by MDR-TB patients and cure rates between 40 and 70%, creating a strong desire for new drugs to combat the condition and potentially reduce hospital stays.*3
- In clinical trials Deltyba demonstrated efficacy and improved long-term treatment outcomes when used in combination with a WHO-recommended background treatment regimen.
- Globally, only 20% of the approximately 450,000 MDR-TB cases are started on treatment and of those, less than half are treated successfully. This low success rate contributes to 170,000 MDR-TB deaths annually.*4
Tokyo, Japan (July 4, 2014) – Otsuka Pharmaceutical Co., Ltd. (Otsuka) today received regulatory approval from the Ministry of Health, Labour and Welfare (MHLW) for Deltyba® (delamanid) as part of an appropriate combination regimen for pulmonary multidrug-resistant tuberculosis (MDR-TB) in adult patients.
Deltyba is a bactericidal agent with a novel mode of action based on the interference of mycolic acid biosynthesis in the Mycobacterium tuberculosis (MTB) cell walls. It also has high activity in vitro against various MTB strains, including those resistant to first-line anti-TB drugs such as isoniazid and rifampicin.*5 Deltyba has been designated as an orphan medicine by the MHLW, meaning that it is a medicine used to treat a rare disease.
The incidence of TB in Japan is 17 per 100,000 people, still a higher rate than in other highly developed countries.*6 Resistance to anti-TB drugs can occur for a number of reasons including misuse or mismanagement, such as failure to complete a full course of treatment due to side effects.*7 The emergence of MDR-TB has become a major global concern imposing a burden on patients to comply with treatment regimens that can last for a minimum of 20 months.*8
With treatment success rates between 40 and 70 percent in Japan, the treatment of MDR-TB patients using only existing anti-TB drugs has created a longstanding yet urgent unmet medical need.*3 This lack of available treatment options contributes to a mortality rate of 21.6% within 5 years and 36.7% within 10 years.*9 Due to low tolerability and emerging resistance to existing therapies, Japan is also characterized as having a high proportion of extensively drug-resistant TB (XDR-TB) cases among its MDR-TB population compared with other Asian countries.*10,*11
Clinical trial results from nine countries showed that 45.4% of study subjects including XDR-TB patients treated with Deltyba 100mg twice daily together with an optimized background regimen (OBR) achieved sputum culture conversion (SCC; a measurement used to determine when a patient is no longer infectious) after two months, a statistically significant increase compared to 29.6% of subjects treated with placebo plus OBR.*12 Importantly, adding Deltyba to an OBR for 6 months was also shown to decrease the mortality rate and improve long-term treatment outcomes for both MDR and XDR-TB patients.*13 Clinical trial results demonstrated that adverse events were evenly distributed in the Deltyba and placebo treatment groups with the exception of QT prolongation. Electrocardiogram QT prolongation was reported in 9.9% of patients receiving Deltyba as 100 mg twice daily plus OBR compared with 3.8% of patients receiving placebo plus OBR. This was not accompanied by any clinical symptoms such as syncope or arrhythmias.*12
Masuhiro Yoshitake, Executive Operating Officer of Otsuka and TB Global Project Leader, stated, “As a Japanese company, we are especially proud that Deltyba is now available in our home country. It took the ingenuity of a large team of Otsuka researchers to arrive at this important milestone. Our work is not yet done, but today’s decision reflects Otsuka’s commitment to patients battling this disease and our long-term goal of stopping MDR-TB nation by nation.”
Dr. Takashi Yoshiyama, Deputy Chief, Center for Respiratory Diseases, Fukujuji Hospital, Japan Anti Tuberculosis Association, stated, "Today, tuberculosis is a curable disease, but because of the rise of MDR-TB and its devastative side effects, many patients – including young people - die or are forced to undergo long-term treatment. New treatment options will help lower the number of cases of this difficult-to-treat form of TB and reduce future infections.”
To help prevent the emergence of resistance to Deltyba and ensure that it remains an option for MDR-TB patients in the future, drug susceptibility testing has been established in specialized institutions and Otsuka has initiated a Responsible Access Program to help guide the proper use of Deltyba.
Earlier this year, Deltyba was granted marketing authorization by the European Commission for use as part of an appropriate combination regimen in adult patients with pulmonary MDR-TB. The company is currently facilitating access within the EU and developing access strategies in high burden countries and countries in which clinical trials have taken place.
About Otsuka Pharmaceutical Co., Ltd.
Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: 'Otsuka-people creating new products for better health worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leading firm in the challenging area of mental health and also has research programs on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate more powerfully than words how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.
Otsuka is a wholly owned subsidiary of Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group. The chairman Akihiko Otsuka is the third generation of Otsuka family members to lead the business, whose origins date from 1921. The Otsuka Group employs approximately 44,000 people globally and its products are available in more than 80 countries worldwide. Net revenues were approximately USD 14.1 billion for fiscal year 2013 (4/1/2013-3/31/2014). Otsuka Pharmaceutical warmly invites you to visit its global website at https://www.otsuka.co.jp/en/
- *1 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 [news release].Tokyo, Japan. Otsuka Pharmaceutical Co., Ltd. 27 March 2013. http://www.otsuka.co.jp/en/company/release/2013/0327_01.html
- *2 Japan MHLW Annual Report on Registrants With Tuberculosis, 2011 (Japanese)
- *3 Takashi Yoshiyama. 84th General Mini-Symposium, V. MDR-TB in Japan, 2. Treatment Outcomes of MDR-TB. Kekkaku. 2010;85(2):128-131 (Japanese)
- *4 WHO Global TB report 2013. http://www.who.int/tb/publications/global_report/en/ (Accessed March 2014)
- *5 Matsumoto M et al. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med. 2006 Nov;3(11):e466
- *6 Japan MHLW, 2013 data ; WHO data, 2012
- *7 CDC Factsheet. Multidrug-Resistant Tuberculosis (MDR TB). http://www.cdc.gov/tb/publications/factsheets/drtb/mdrtb.htm (Accessed March 2014)
- *8 Falzon D et al. WHO guidelines for the programmatic management of drug-resistant tuberculosis:2011 update. Eur Respir J 2011;38:516-528
- *9 Takashi Yoshiyama. 73rd General Symposium, I. Multidrug-Resistant Tuberculosis, 3. MDR-TB Epidemiology. Kekkaku. 1998;73(11):665-672 (Japanese)
- *10 WHO Stop TB Department, Multidrug and extensively drug-resistant TB (M/XDR-TB), 2010 Global Report on Surveillance and Response, World Health Organization
- *11 Tuberculosis Research Committee (Ryoken): Drug-resistant Mycobacterium tuberculosis in Japan: a nationwide survey, 2002. Int J Tuberc Lung Dis. 2007; 11: 1129-1135
- *12 Gler MT et al. Delamanid for multidrug-resistant pulmonary tuberculosis. N Engl J Med. 2012 Jun 7; 366(23): 2151-60
- *13 Skripconoka V, Danilovits M, Pehme L, Tomson T, Skenders G, et al. (2013) Delamanid Improves Outcomes and Reduces Mortality for Multidrug-Resistant Tuberculosis. Eur Respir J. 41: 1393-1400.
Information in this news release was current as of the original release date.