根据4月12日发布的一项后期临床试验结果，Intercept制药公司开发的药物Obeticholic acid对主要发生在中年妇女中的一种罕见肝脏疾病体征有明显的改善，降低了患者的肝移植需求及死亡风险。

在接受Obeticholic acid治疗的原发性胆汁性肝硬化症患者中，大约有一半的患者达到了研究的主要目标，相比之下，接受安慰剂治疗的患者中只有10%的患者达到研究的主要目标。

临床研究的复合终点是碱性磷酸酶至少下降15%，血清碱性磷酸酶的活性低于正常上限的1.67倍，而胆红素在正常范围内， 碱性磷酸酶是用来表示肝脏疾病严重程度的一种生物标记物。

“ 碱性磷酸酶是生存期真正最好的预后因子，” Frederik Nevens在一次电话采访中说，他是这项研究的主要研究者，也是鲁汶大学肝脏病学系主任。他称试验结果“非常、非常重要。”这项由217名患者参与的3期Poise研究结果在伦敦举行的欧洲肝脏研究协会(EASL) 年会上得到发布。

原发性胆汁性肝硬化(PBC)是将胆汁酸从肝脏输出的导管出现自身免疫破坏，导致有毒的胆汁酸逐渐积聚而引起。该疾病引起渐进性肝损伤，常常导致需要肝移植或死亡。

Obeticholic acid是一种新型药物，研究用于那些对旧标准治疗药物熊去氧胆酸没有充分应答或不能耐受的患者。Intercept制药表示，该公司打算在今年晚些时候向美国和欧洲提交这款药物的上市申请。鉴于这款药物用于治疗罕见疾病，它被美国FDA授予孤儿药资格，如果获得上市批准，它将获得7年的市场专营权。

Obeticholic acid还在测试用来治疗一种更为常见的脂肪肝——非酒精性脂肪肝炎。该款药物一项用于治疗此种适应症的2期临床研究因其确切疗效而被提前中止。Nevens表示，他预测这款使用方便、日服一次的药片会改变原发性胆汁性肝硬化的医疗实践。

患者在长达一年的研究中病情变得更加温和，大多数患者使用老药已大约10年时间。在试验中，患者接受5mg或10mg或安慰剂治疗。5mg用药组中，经过6个月治疗后对药物没有充分应答的患者，在剩余的6个月剂量增加到10mg。

5毫克剂量组及那些转换到更高剂量的患者中有46%的人达到研究的主要目标，而最初接受10mg治疗的患者有47%的人达到研究的主要目标。对达到主要目标的患者进行肝脏检测，检测结果显示病情实现好转。相比之下，“安慰剂组患者的病情有恶化倾向。

使用这款药物时最常见副作用是严重瘙痒，这也是疾病本身的一种症状。低剂量时瘙痒往往没那么严重，在早期试验中测试更高剂量时，瘙痒更加糟糕。10mg剂量组有10%的患者因瘙痒在试验中出组，但在起始剂量为5mg，后来又转换成10mg的患者中，仅有1%的患者中止治疗。总体来说，这款药物是安全的。

Intercept's liver disease drug proves highly effective in study

A drug being developed by Intercept Pharmaceuticals Inc led to significant improvement in signs of a rare liver disease that primarily affects middle-aged women, likely reducing the risk of need for liver transplant and of death, according to results of a late-stage clinical trial presented on Saturday.

Nearly half the patients suffering from primary biliary cirrhosis who received the drug, obeticholic acid, achieved the primary goals of the study, compared with 10 percent for those who received a placebo, researchers said.

The composite main goal of the study was to achieve at least a 15 percent reduction in levels of alkaline phosphatase, a biomarker for severity of the liver disease, serum alkaline phosphatase activity of less than 1.67 times the upper limit of normal and bilirubin within normal limits.

"Reduction in alkaline phosphatase is really the best prognostic factor for survival," Dr. Frederik Nevens, the study's lead investigator and chairman of the department of hepatology at the University of Leuven, in Belgium, said in a telephone interview.

He called results "highly, highly significant."

Results of the 217-patient Phase III study, called Poise, were presented at the annual meeting of the European Association for the Study of the Liver (EASL) in London.

Primary biliary cirrhosis (PBC) is caused by autoimmune destruction of the ducts that transport bile acids out of the liver, resulting in toxic buildup of bile acids. The disease causes progressive liver damage and often leads to need for a liver transplant or to death.

Obeticholic acid, a first-in-class drug, is being studied for those who have an inadequate response to, or cannot tolerate, standard treatment with an older generic medicine called ursodeoxycholic acid.

Intercept said it plans to apply for approval later this year in the United States and Europe for the medicine, which has received orphan drug designation. In the United States orphan drug status, given to drugs that treat rare diseases, comes with seven years of marketing exclusivity if approved.

Obeticholic acid is also being tested to treat a much more common fatty liver disease called nonalcoholic steatohepatitis. When a Phase II study of the drug for that condition was stopped early because the medicine was clearly effective, Intercept's stock price nearly quadrupled to ab0ut $300 a share.

Nevens said he expects the convenient once-a-day pill to change medical practice for primary biliary cirrhosis.

"Patients are dying and needing liver transplants. If this drug comes on the market, I see no reason why we wouldn't use it," he said.

Patients in the year-long study had a moderate form of the disease, and most on average had been taking the older medicine for ab0ut 10 years.

They received either 5 milligrams or 10 mg of obeticholic acid or a placebo. Those in the 5 mg group who had not had an adequate response after six months were increased up to 10 mg for the final six months.

Forty-six percent in the 5 mg group and those who switched to the higher dose and 47 percent in the original 10 mg group achieved the primary goal of the study, researchers said.

Liver tests on those who achieved the primary goal fell to levels that correlate to improvement in the outcome of these patients, said Nevens. In contrast, "there was a tendency of worsening of liver disease in the placebo group," he said.

The most common side effect with the drug was severe itching, which is also a symptom of the disease. The itching tends to be less severe with lower doses and had been much worse in earlier trials testing far higher doses, Nevens said.

Ten percent of those in the 10 mg group dropped out of the trial due to itching, but only one patient who started on 5 mgs and later switched to 10 mg discontinued treatment.

"Overall the drug is safe," Nevens said.

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