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Prothena治疗罕见病AL型淀粉样变性药物NEOD001临床前期研究取得进展

  1. AL型淀粉样变性
  2. NEOD001
  3. Prothena
  4. 罕见病

来源:生物谷 2014-12-04 15:01

--Prothena公司最近宣布,公司正在开发的一种用于治疗名为AL型淀粉样变性的罕见病药物NEOD001最近在一项临床I/II期研究中表现出良好的效果。

2014年12月4日讯 /生物谷BIOON/ --Prothena公司最近宣布,公司正在开发的一种用于治疗名为AL型淀粉样变性的罕见病药物NEOD001最近在一项临床I/II期研究中表现出良好的效果。这也坚定了Prothena公司进一步将其推入临床三期研究的决心。在此次有14名患者参加的早期临床研究中,超过半数的患者在NT-proBNP的指标上有显著下降,这一指标也是衡量AL型淀粉样变性患者死亡的重要参数。此外,有6名患者的蛋白尿程度下降了42.9%之多。这一指标也表明患者的肾小球透过功能有了显著的提升。

目前,等待Prothena公司进行的工作还有很多。研究人员正在进行七种不同剂量的患者组,以确定不同器官出现问题的AL型淀粉样变性患者能否对药物做出反应;同时研究人员还将在即将开始的临床三期研究中考察这种药物对患者心血管和肾脏的潜在影响。预计这一研究将在欧洲和美国超过50个地点同时进行,研究人员预计整个志愿者招募工作将花费18-30个月,而随后的临床三期研究时间将在12-18个月之间。Prothena公司希望这一药物能为正饱受这一疾病困扰的患者提供新的希望。

公司CSO Gene Kinney介绍说,根据历史数据统计,此前患者接受未受批准的疗法时,分别有26.5%和24%的患者出现了心血管和肾脏问题。

Prothena公司是2012年从Elan公司独立出的新公司,公司的总部设在爱尔兰首都都柏林,并在旧金山设有实验室。此前Elan公司一直是业内著名的阿尔兹海默症等神经退行性疾病药物的研发者。而众所周知,淀粉样蛋白在这些疾病中都起到了关键作用。因此,Prothena公司在这一领域中可以说已经有了丰富的经验。(生物谷Bioon.com)

详细英文报道:

A small Phase I/II study of Prothena's lead drug produced an encouraging round of initial responses among patients with AL amyloidosis, a rare threat to organs. And now company execs say they're going straight into a Phase III study of NEOD001 so they can build a case for regulators.

Among 14 cardiac patients who were evaluable at this stage, the biotech says that half demonstrated a significant reduction in levels of NT-proBNP, a biomarker they used which can indicate their risk of dying. And 6 of 14 evaluable renal patients--42.9%--had a significant drop in proteinuria in the absence of estimated glomerular filtration rate (eGFR) worsening.

Historical rates of response "would have predicted 26.5% cardiac and approximately 24% renal response rates in patients treated solely with off-label standard of care," said Chief Scientific Officer Gene Kinney.

Shortly after the company released the early data and plans for late-stage work on Tuesday evening, the news from the company took a sudden and unexpected twist. Prothena CEO Dale Schenk, the former CSO at Elan, posted a letter alerting investors to his recent diagnosis of pancreatic cancer. "I am pleased to report that the cancer was caught early and I am doing well," he wrote, adding that he expected to stay active with the company as he underwent treatment. Being a scientist, he added, was a great benefit at a time like this.

Prothena ($PRTA) was spun out of Elan (which was later acquired for its royalty stream) back in 2012, giving the biotech a chance to sort through its R&D assets to come up with an optimal portfolio of experimental therapies. Longtime observers of the biotech scene will recall that Elan was an early pioneer in Alzheimer's, advancing one of the first amyloid beta drugs (bapineuzumab) under J&J's guidance through a high-profile Phase III flop. And Kinney is the former head of research at J&J's Janssen Alzheimer Immunotherapy R&D group.

But there was still a decade's worth of work on amyloid and amyloid diseases to back up their efforts on AL amyloidosis, says Kinney. The disease is caused by the misfolding of a protein, with amyloid deposits building up in organs like the heart and kidneys and causing them to fail.

Prothena is an unusual transatlantic hybrid, with the company based in the low-tax environs of Dublin and a lab in the South San Francisco biotech hub. Neil Woodford, who's been getting more deeply involved in biotech investing, recently gambled $50 million on Prothena's pipeline.

The study now being discussed is being done in two parts. The first was an open-label study doing dose-escalation work on 7 cohorts of patients with any systemic organ involvement where investigators were looking at biomarkers of the disease. The second, upcoming segment will run parallel with the Phase III with a closer focus on cardiac and renal involvement.

"We'll be initiating Phase III when we make this announcement," Kinney toldFierceBiotech. The Phase III will be run as a multinational study with 50 to 60 sites in the U.S. and Europe. Investigators will have 18 to 30 months for recruitment and then expect to follow patients for 12 to 18 months of therapy.

Kinney says there are about 15,000 cases of AL amyloidosis  in the U.S. and Europe, though he suspects that the disease is underdiagnosed right now. And the biotech isn't alone in the field. Takeda has the most advanced program in the clinic for amyloidosis with ixazomib, and is also jumping from Phase I straight into Phase III after getting a "breakthrough" drug designation from the FDA.

"NEOD001 potentially holds significant promise for patients with AL amyloidosis as we now see clinically meaningful decreases in both cardiac and renal biomarkers with monthly NEOD001 infusions," said Tufts Professor Raymond L. Comenzo. "NEOD001 appears to be the first agent that works directly to address the buildup of light-chain (AL) amyloid in organs. The results presented today strongly support moving into a Phase III trial, which I believe is designed to test whether or not NEOD001 provides meaningful clinical benefit for patients with AL amyloidosis."

 

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