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TB Alliance推进结核病治疗方案PaMZ进入里程碑III期临床

2014年4月24日讯 /生物谷BIOON/ --全球结核病药物研发联盟(TB Alliance)4月23日宣布,基于早期研究的积极数据,将推进新型结核病治疗方案PaMZ至里程碑意义的全球III期临床。该公告由微软联合创始人、比尔和梅琳达·盖茨基金会(Bill & Melinda Gates Foundation)联合主席比尔盖兹(Bill Gates)宣布。

PaMZ由新的结核病候选药PA-824、抗生素莫西沙星以及现有的结核药吡嗪酰胺组成,该疗法旨在显著缩短和简化药物敏感性(drug-sensitive)和耐药性(drug-resistant)结核病(tuberculosis,TB)的治疗。

早期阶段的研究表明,PaMZ方案治愈时间更短,更简单,更安全,且与现在的多重耐药性结核(MDR-TB)药物相比更加便宜。全球结核病药物研发联盟预计,PaMZ方案有望极大缩短治愈多重耐药性结核(MDR-TB)的时间,从2年时间缩短至短短6个月,同时将淘汰注射剂的使用,并可使MDR-TB治疗费用降低高达90%。此外,PaMZ方案有望与常用的HIV药物兼容,并帮助数以百万计的TB/HIV共感染者。

TB联盟总裁兼CEO Mel Spigelman指出,结核病患者,尤其是耐药性结核病患者,迫切需要一种无需注射、服药更少、毒性更低、给药更简单、成本低得多的治疗方案。

III期STAND研究将在横跨非洲、亚洲、东欧和拉丁美洲的50个研究点展开,将测试新型三合一方案PaMZ作为一种更短、更简单、更安全的疗法用于药物敏感性和耐药性结核病的治疗。2012年7月发表于《柳叶刀》的一项II期研究表明,PaMZ方案可在2周内杀死患者体内超过99%的结核杆菌。

PaMZ方案的早期研究得到了比尔和梅琳达·盖茨基金会(BMGF)、英国国际开发部(DFID)、澳大利亚署外事(DFAT)、美国国际开发署(USAID)、爱尔兰援助机构(Irish Aid)以及国际合作总司(DGIS)提供。

在全球范围内,结核病是继艾滋病之后的第二大成年人杀手,每年有近二百万人死于结核病。(生物谷Bioon.com)

英文原文:New Tuberculosis Drug Regimen Will Move to Landmark Phase 3 Clinical Trial

STAND trial will test the first regimen designed to significantly shorten and simplify the treatment of drug-sensitive and drug-resistant TB

Based on positive results from earlier clinical studies, TB Alliance is advancing the first-ever drug regimen designed to treat both drug-sensitive and some forms of multi-drug resistant tuberculosis (TB) to a global Phase 3 clinical trial.

The announcement by Bill Gates, co-chair of the Bill & Melinda Gates Foundation, accompanied a commitment of significant funding by the Gates Foundation to determine the safety and efficacy of the new drug regimen, which is known as PaMZ. Mr. Gates called on other organizations to support the effort to develop new treatments for TB, a disease that kills an estimated 1.3 million people annually and remains a leading cause of death globally, especially among people who are co-infected with HIV.  

"The results from early phase research suggest that this new drug regimen could provide the breakthrough we need to accelerate progress against this deadly and dangerous disease," said Mr. Gates. "PaMZ could dramatically reduce the time required to cure drug-resistant TB from two years to just six months, and it could cut the cost of curing drug-resistant TB in low-income countries from thousands of dollars to just a fraction of that cost. Now we need funders to step forward to make next-generation TB drugs like PaMZ a reality."

Limitations in standard treatment for TB remain a strong barrier to TB control. The treatment and cure of a typical case of drug-sensitive TB currently takes between six and nine months and the drug therapy is long, complicated, and can cause severe side effects. Currently, people with drug-resistant TB require a minimum of 18 to 24 months of treatment. This more extensive therapy requires more than 12,000 pills and daily injections for at least 6 months. The long duration of MDR-TB treatment, combined with the pain and side effects that treatment causes, help to explain why only just over half (53 percent) of patients who currently enter therapy for MDR-TB complete their full course of medicines.

The PaMZ regimen shows promise to significantly shorten therapy, particularly for some forms of MDR-TB. It will be tested in a Phase 3 clinical trial named STAND (Shortening Treatments by Advancing Novel Drugs). If successful, the regimen would eliminate the need for injectable drugs and reduce the cost of MDR-TB therapy in some countries by more than 90 percent in those patients whose TB organisms are sensitive to the three drugs. It also promises to be compatible with commonly used HIV drugs, helping the millions of people co-infected with TB/HIV.

“TB patients, especially those with drug-resistant TB, urgently need cures  that eliminate the need for injectable therapies, require taking fewer pills for a shorter period of time, are less toxic, simpler to administer and cost much less money,” said Dr. Mel Spigelman, president and CEO of TB Alliance, an international non-profit working to develop improved TB treatments. “The STAND trial brings us closer to an era of high-impact drug regimens instead of where we are today, relying on the relics of the mid-20th century.”

The STAND trial will span some 50 study sites across Africa, Asia, Eastern Europe and Latin America. It will test the novel three-drug regimen PaMZ as a shorter, simpler and safer treatment for drug-sensitive and drug-resistant TB. The development of the PaMZ regimen is projected to save years of time by having tested new drugs simultaneously as a “drug regimen” instead of one-by-one.

PaMZ is a three-drug regimen comprised of two candidate drugs that are not yet licensed for use against TB: PA-824 (Pa) and moxifloxacin (M), and one existing antibiotic used in TB treatment today, pyrazinamide (Z). Earlier study results show PaMZ’s potential to treat both drug-sensitive and drug-resistant patients with the same oral therapy, and to dramatically shorten treatment times for some patients. In July 2012, a two-week study published in The Lancet showed that PaMZ appeared to kill the patients’ bacteria more quickly than standard therapy after starting treatment. Findings from a subsequent two-month study are expected to be published later this year.

Support for earlier research of the PaMZ regimen was provided by the Bill & Melinda Gates Foundation (BMGF), the United Kingdom Department for International Development (DFID), the Australia Department for Foreign Affairs (DFAT), US Agency for International Development (USAID), Irish Aid, and the Directorate-General for International Cooperation (DGIS).

While the TB Alliance hopes to launch the STAND trial by the end of this year, Spigelman noted the date will be subject to obtaining adequate funding commitments.

“We thank all our supporters to date, as without their investment, the highly promising PaMZ regimen would not have reached this critical stage,” said Spigelman. “We need new and expanded commitments for the STAND trial, however, if we are to realize the significant potential of this treatment to save millions of lives.”

关键词:结核病,多耐药结核,TB,PaMZ

信息来源:生物谷