Efficacy results of Otsuka’s delamanid (Deltyba™) for XDR-TB published in the New England Journal of Medicine

Delamanid plus a background treatment regimen rendered more patients non-infectious after two months compared to placebo plus a background treatment regimen. ⁱ

By 2014, 100 countries, including the U.S., reported at least one case of XDR-TBⁱ, 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.ⁱⁱ

TOKYO, July 15, 2015--Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announced that data from a post-hoc subset analysis of its Phase IIb clinical trial 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)ⁱ. 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=0.1108).ⁱ

“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 if confirmed, 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.ⁱⁱ 100 countries have reported at least one case of this dangerous strain, including the U.S.,ⁱⁱⁱ where contact tracing is currently ongoing after an infected patient exposed individuals in at least three states to the disease.ⁱⁱⁱ

“The study’s important findings reaffirm Otsuka’s commitment to continued research into 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 potential progress against this deadly strain.”

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

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 to those with placebo added (29.6%).^x

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.^xi

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.ⁱⁱⁱ 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.^xi Approximately 480,000 people developed MDR-TB in 2013.ⁱⁱⁱ

About Otsuka Pharmaceutical Co., Ltd.

Otsuka Pharmaceutical 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. Otsuka Pharmaceutical, Japan’s second-largest drug company, is a wholly owned subsidiary of Otsuka Holdings Co., Ltd. The Otsuka Group employs approximately 43,000 people globally and its products are available in more than 80 countries worldwide.

For more information about Otsuka visit: https://www.otsuka.co.jp/en/

ⁱ World Health Organization (WHO). XDR-TB: Extensively Drug-resistant TB. http://www.who.int/tb/challenges/mdr/xdr/en/ (Accessed June 2015)
ⁱⁱ World Health Organization (WHO). Global Tuberculosis Report 2014. http://apps.who.int/iris/bitstream/10665/137094/1/9789241564809_eng.pdf (Accessed June 2015)
ⁱⁱⁱ Reuters. U.S. health officials seek people who may have contacted TB patient. June 10, 2015. http://in.reuters.com/article/2015/06/09/us-usa-health-tuberculosis-idINKBN0OP1W420150609 (Accessed June 2015).
^iv Matsumoto M, Hashizume H, Tomishige T, 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.
^v European Medicines Agency. Deltyba’s European public assessment report (EPAR) summary for the public. EMA/731960/2013 EMEA/H/C/002552 http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/002552/WC500166235.pdf (Accessed June 2015)
^vi Pharmaceuticals and Medical Devices Agency (PMDA). New Drugs Approved in June 2014. http://www.pmda.go.jp/files/000197902.pdf (Accessed June 2015).
^vii Korea Food and Drug Administration (KFDA). http://ezdrug.mfds.go.kr/kfda2 (Accessed July 2015.)
^viii World Health Organization (WHO). Interim guidance on the use of delamanid in the treatment of MDR-TB. October 2014. http://www.who.int/tb/features_archive/delamanid/en/ (Accessed June 2015)
^ix World Health Organization (WHO). Executive Summary: The Selection and Use of Essential Medicines (2015). Report of the 20^th WHO Expert Committee on the Selection and Use of Essential Medicines. 20-24 April 2015. http://www.who.int/medicines/publications/essentialmedicines/Executive-Summary_EML-2015_7-May-15.pdf (Accessed June 2015)
^x Gler MT, Skripconoka V, Sanchez-Garavito E, et al. Delamanid for multidrug-resistant pulmonary tuberculosis. N Engl J Med. 2012;366:2151-60
^xi World Health Organization (WHO). Shorter treatment regimens for multidrug-resistant tuberculosis. May 2013. http://www.who.int/tb/publications/Short_TB_regimens.pdf (Accessed June 2015).

Source: Otsuka Pharmaceutical Co., Ltd.