Deltyba（delamanid）——时隔40年首次批准抗结核上市新药.
2014年5月2日，大冢制药（Otsuka Pharmaceutical）宣布，结核新药Deltyba（delamanid）获欧盟委员会（EC）批准，用作组合方案的一部分，用于肺耐多药结核病（MDR-TB）成人患者的治疗。此前，欧洲药品管理局（EMA）于2008年授予Deltyba孤儿药地位。
Deltyba是一种具有新颖作用模式的杀菌剂，能够干扰结核分枝杆菌（MTB）细胞壁的代谢。该药在体外实验中，对多种不同的MTB菌株均具有很高的杀菌活性，包括耐一线抗结核药物（如异烟肼和利福平）的菌株。
来自9个国家的临床试验数据表明，与安慰剂相比，Deltyba（100mg，BID即每日2次）联合一种优化的背景疗法（Optimized Background Regiment，OBR）在痰培养转化（sputum culture conversion，SCC）方面取得了统计学意义的显著增加（45.4% vs 29.6%）。SCC是一种评价措施，用于判断患者不再受感染。
结核病（tuberculosis）是由结核杆菌（Mycobacterium tuberculosis）引发的一种传染性疾病，主要影响肺部。在欧盟，结核病是一种罕见病，据2011年预计数据，结核病在欧盟的发病率约为万分之2.3。耐多药结核病是指至少对异烟肼（ isoniazid）和利福平（rifampicin）耐药的结核病，这2种药物是用于结核病标准治疗中的2种主要的抗结核药物。据估计，在全球范围内，每年发生约45万例耐多药结核病病例，相当于全球每年结核病的5%。
近年来，由于缺乏新的治疗选择，耐药性结核病所导致的公共健康问题迅速增加。耐多药结核病与高的死亡率相关，已构成了严重的公共健康威胁，因为感染了耐药菌株的患者无法获得充分的治疗，并有可能传播感染。
2014年3月，强生（JNJ）结核病新药Situro（bedaquiline）获欧盟委员会（EC）有条件批准（conditional approval），作为组合疗法的一部分，用于因耐药性或耐受性使得一种有效治疗方案不能用于其临床治疗的肺部耐多药结核病（MDR-TB）成人患者的治疗。
注：本品可采购（采购者请提前20个工作）

Otsuka Wins European Marketing Authorization for Deltyba™ (delamanid)

First grant of a marketing authorization of Otsuka’s novel drug for multidrug-resistant tuberculosis (MDR-TB).
Deltyba is a new treatment option for MDR-TB. Globally, only half of MDR-TB cases experience successful outcomes, which leads to 170,000 deaths annually, according to WHO.
TB was one of the first research areas pursued by Otsuka’s research institute when it was established in 1971 by then-president Akihiko Otsuka. Otsuka is currently the largest funder of TB drug development worldwide.
TOKYO--(BUSINESS WIRE)--Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announced that the European Commission has granted a marketing authorization for Deltyba™ (delamanid) for use as part of an appropriate combination regimen for pulmonary multidrug-resistant tuberculosis (MDR-TB) in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability.
Deltyba is a bactericidal agent with a novel mode of action that interferes with the metabolism of 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.
Deltyba was designated as an orphan medicine in 2008 meaning that it is a medicine used to treat a rare disease. Clinical trial results from  countries showed that study subjects treated with Deltyba 100mg twice daily together with an optimized background regimen (OBR) achieved a statistically significant increase in sputum culture conversion (SCC) after two months (45.4% of study subjects) compared to those treated with a placebo (29.6% of study subjects). SCC is a measurement used to determine when a patient is no longer infectious.
Akihiko Otsuka, Chairman of Otsuka, stated, “It is very pleasing to me that a new drug developed by Otsuka Pharmaceutical has become available to patients in Europe with MDR-TB. Currently, MDR-TB is a serious problem there. When rifampicin was developed half a century ago, it seemed that the world’s TB problem was over. But I specifically selected TB as a research theme for our company. I knew that someone had to do this research because TB was still a huge public health issue in Asia.”
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 potential side effects.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. With a treatment success rate of less than 50% globally, the treatment of MDR-TB patients using only existing anti-TB drugs has created an urgent unmet medical need.
“The TB community has waited a long time for a new medication for MDR-TB,” said Dr. Wiel de Lange, an MDR-TB expert at the University Medical Center in Groningen, the Netherlands. “With increasing rates of resistance to existing medications and globally less than half of all MDR-TB cases successfully treated, Deltyba is clearly a welcome new option.”
Taro Iwamoto, President of Otsuka Pharmaceutical, commented, “I am very gratified that Deltyba has been granted a marketing authorization as a first-in-class, anti-TB drug in Europe – a dream we have held since the establishment of our research institute. There are still many patients throughout the world who suffer from MDR-TB. I hope Deltyba will contribute to the improvement of TB treatment.”
To ensure that in the future patients can continue to benefit from Deltyba, Otsuka has invested in the creation of a Responsible Access Programme (RAP) to help safeguard against the possible emergence of resistance to the medicine. The RAP includes strict distribution control, professional medical education about the proper administration of Deltyba in combination with other MDR-TB drugs, and a comprehensive patient registry to track the safety and efficacy of Deltyba. Otsuka remains committed to providing access to Deltyba in underserved populations and will apply for marketing authorization in high burden countries and countries in which clinical trials have taken place.
About Deltyba
Deltyba is indicated for use as part of an appropriate combination regimen for pulmonary multidrug-resistant tuberculosis (MDR-TB) in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. The recommended dose for adults is 100 mg twice daily for 24 weeks.3 Clinical trial results showed 45.4% of study subjects treated with Deltyba 100 mg twice daily plus OBR, achieved sputum culture conversion (SCC), a measurement by which a patient is no longer infectious, after two months compared to 29.6% of those treated with placebo plus OBR, representing a statistically significant 53% increase.
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 compared to 3.8% of patients receiving placebo plus OBR. This was not accompanied by any clinical symptoms such as syncope or arrhythmias.5
About TB/MDR-TB
According to the WHO, tuberculosis is the second leading cause of death among infectious diseases. Every year, approximately 8.6 million people become sick, and nearly 1.3 million people die from TB or TB-related causes.1 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.8 Treatment resistance emerges from the misuse of TB therapies, including poor drug supply, poor drug quality, or patients’ inability to complete their treatment regimens.6 Twenty-seven countries around the world account for 90% of the MDR-TB burden.