百健艾迪和艾伯维单抗DAC——HYP多发性硬化症III期DECIDE研究达优越性疗效终点

/生物谷BIOON/ --百健艾迪(Biogen Idec)和艾伯维(AbbVie)6月16日公布了III期DECIDE临床试验的阳性顶线数据，该研究旨在评估每月一次皮下注射剂型高产工艺daclizumab(daclizumab high-yield process，DAC HYP，达克珠单抗HYP)作为一种潜在的药物用于复发缓解型多发性硬化症(RRMS)治疗时相对于肌肉注射干扰素β-1a(IFNβ-1a)的优越性。研究结果表明，与IFNβ-1a相比，DAC HYP使年度复发率(ARR)显著降低了45%(p<0.0001)，达到了优越性的主要终点。

DECIDE研究的结果令人振奋，与当前MS标准护理相比，DAC HYP表现出了强劲的疗效。DAC HYP具有新颖的作用机制，作为一种每月一次疗法，如果获批，将成为多发性硬化症(MS)患者的一个重要的治疗选择。

百健艾迪和艾伯维计划与监管当局共同合作，确定DAC HYP的监管提交时间表。该项研究的详细数据将提交至未来举行的科学会议。

关于DAC HYP：

高产工艺达克珠单抗(DAC HYP)是达克珠单抗(daclizumab)的皮下剂型，正调查用于多发性硬化症(MS)中最常见类型复发缓解型多发性硬化症(RRMS)的治疗。DAC HYP是一种新型人源化单抗，结合T细胞表面的受体亚基CD25。MS患者中，CD25呈高水平表达，T细胞被异常激活。DAC HYP能够调节IL-2信号通路，而不会引起免疫细胞的消耗。

T细胞据信在诸如MS等自身免疫疾病中异常激活。DAC HYP被认为通过降低异常激活的T细胞和促炎性淋巴组织诱导细胞、增加CD56bright NK 细胞发挥作用。NK细胞是一类重要的细胞，能够靶向作用于在MS中发挥关键作用的激活免疫细胞，帮助调节免疫系统。(生物谷Bioon.com)

英文原文：Biogen Idec and AbbVie Announce Positive Top-Line Results from Phase 3 Study Investigating Daclizumab High-Yield Process in Multiple Sclerosis

− DAC HYP DEMONSTRATED SUPERIORITY OVER INTERFERON BETA-1A IN ANNUALIZED RELAPSE RATE – − POSITIVE RESULTS SET STAGE FOR REGULATORY FILINGS –

Jun 16, 2014

CAMBRIDGE, Mass. and NORTH CHICAGO, Ill. – June 16, 2014 – Today Biogen Idec (NASDAQ: BIIB) and AbbVie (NYSE:ABBV) announced positive top-line results from the Phase 3 DECIDE clinical trial, designed to evaluate the superiority of once-monthly, subcutaneous daclizumab high-yield process (DAC HYP) when compared to intramuscular interferon beta-1a (IFN β-1a), as a potential treatment for relapsing-remitting multiple sclerosis (RRMS), the most common form of multiple sclerosis (MS). Results showed that DAC HYP was superior on the study’s primary endpoint, demonstrating a statistically significant 45 percent reduction in annualized relapse rate (ARR) compared to IFN β-1a (p<0.0001).

“The results of the DECIDE study are compelling, with DAC HYP demonstrating robust efficacy compared to a current standard of MS care,” said Gilmore O’Neill, vice president, Global Neurology Clinical Development, Biogen Idec. “As a potential once-monthly therapy with a novel mechanism of action, we believe that, if approved, DAC HYP will be an important treatment option for people living with MS.”

“The positive results in the DECIDE study represent achievement of an important milestone in the development of DAC HYP as a potential new treatment option for MS patients,” said Michael Severino, M.D. executive vice president, Research and Development and chief scientific officer , AbbVie. “Together, the companies are committed to working with regulatory agencies on filing plans for DAC HYP.”

DAC HYP showed superiority on the first secondary endpoint, number of new or newly enlarging T2-hyperintense lesions at week 96, with a 54 percent reduction relative to IFN β-1a (p<0.0001). On the second secondary endpoint, DAC HYP reduced the risk of three month confirmed disability progression as measured by the Expanded Disability Status Scale (EDSS) by 16 percent over IFN β-1a, which was not statistically significant (p=0.16). Using a pre-specified sensitivity analysis that accounted for 67 patients who did not have a confirmatory disability assessment, DAC HYP showed a 21 percent reduction in the risk of sustained disability progression (p=0.047).

The safety profile of DAC HYP in the study was consistent with what has been observed in prior studies. The overall incidence of adverse events was comparable across the DAC HYP and IFN β-1a treatment groups. In patients treated with DAC HYP compared to IFN β-1a, there was an increased incidence of serious infections (4 percent vs. 2 percent), serious cutaneous reactions (2 percent vs. < 1 percent), and elevations of liver transaminases greater than 5 times the upper limit of normal (6 percent vs. 3 percent). There were 4 deaths in the IFN β-1a group and 1 death in the DAC HYP group, none of which was considered treatment related.

Biogen Idec and AbbVie plan to work with regulatory agencies to determine appropriate timelines for filing. The companies intend to present detailed results from DECIDE at a future medical conference.

About DECIDE

DECIDE was a two to three year, Phase 3, global, randomized, double-blind, multicenter study designed to determine if DAC HYP would provide superior outcomes for certain clinical endpoints compared to treatment with IFN β-1a. The study enrolled more than 1,800 people with RRMS in 28 countries. DECIDE was an active comparator study with two groups: 150 mg of subcutaneous DAC HYP every four weeks was compared to IFN β-1a 30 mcg intramuscular injection once weekly.

The primary endpoint in DECIDE was the reduction in ARR. Secondary endpoints included the number of new or newly enlarging T2-hyperintense lesions, the proportion of patients with sustained disability progression (EDSS), the proportion of relapse-free patients and the proportion of patients who experienced a worsening physical impact score on the Multiple Sclerosis Impact Scale (MSIS-29).

After completing the DECIDE study, patients have the option to participate in an open-label extension study called EXTEND.

The DAC HYP development program also includes the previously completed pivotal, placebo controlled, double-blind SELECT study.

About Daclizumab High-Yield Process

DAC HYP is a new form of humanized monoclonal antibody that binds to CD25, a receptor subunit that is expressed at high levels on T-cells that become abnormally activated in MS. DAC HYP modulates IL-2 signaling without causing general immune cell depletion. DAC HYP is believed to work by decreasing abnormally-activated T-cells and pro-inflammatory lymphoid tissue inducer cells, and increasing CD56bright natural killer (NK) cells, important cells that help regulate the immune system.

Biogen Idec and AbbVie are jointly developing DAC HYP.

About Avonex® (Interferon b-1a)

AVONEX is one of the most prescribed treatments for relapsing forms of MS worldwide. AVONEX is indicated for the treatment of patients with relapsing forms of MS to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. Patients with MS in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with MS.

Symptoms of depression, suicidal ideation, or psychosis, and cases of suicide, have been reported with increased frequency with patients receiving AVONEX. Severe hepatic injury, including cases of hepatic failure has been reported rarely in patients. Rare cases of anaphylaxis have been reported.

While beta interferons do not have any known direct cardiac toxicity, cases of congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure have been reported in patients without known predisposition. Decreased peripheral blood counts have been reported from post-marketing experience. Seizures have been reported in patients using AVONEX, including patients with no prior history of seizure.

Autoimmune disorders of multiple target organs have been reported. Routine periodic blood chemistry, hematology, liver function, and thyroid function tests are recommended. AVONEX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The most common side effects associated with AVONEX treatment are flu-like symptoms, including chills, fever, myalgia, and asthenia.