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百健艾迪Zinbryta关键III期击败全球TOP2药物Avonex

来源:生物谷 2014-09-13 12:44

2014年9月13日讯 /生物谷BIOON/ --百健艾迪(Biogen Idec)和合作伙伴艾伯维(AbbVie)近日公布了多发性硬化症(MS)单抗药物Zinbryta(daclizumab,达克珠单抗,高产工艺)III期DECIDE研究的完整数据,该项研究在复发缓解型多发性硬化症(RRMS,最常见类型)患者中开展,Zinbryta每月皮下注射一次,数据表明,与每周一次肌肉注射药物Avonex(干扰素β-1a)相比,Zinbryta在减少疾病活动方面表现出了统计学意义的显著改善,包括降低年度复发率和新的脑部损伤的形成。

Avonex是百健艾迪最畅销的多发性硬化症(MS)药物,位列MS市场全球TOP 2,2013年销售额高达30亿美元,该药每周肌肉注射一次,目前百健艾迪也推出了长效版Avonex,每2周注射一次。DECIDE研究的结果令人振奋,与当前MS标准护理相比,Zinbryta表现出了强劲的疗效。Zinbryta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。

DECIDE是一项为期2-3年的全球性、随机、双盲III期研究,在1800多例RRMS患者中开展,调查了Zinbryta在特定临床终点方面是否能提供优越于Avonex的临床预后。数据表明,与Avonex治疗组相比,Zinbryta治疗组年度复发率(ARR)降低45%,数据具有统计学显著差异(p<0.0001),达到了研究的主要终点。次要终点方面:(1)96周时,Zinbryta在减少新发或新扩大的T2高信号病灶数目方面表现出了优越性,减少幅度比Avonex高54%,具有统计学显著差异(p<0.0001);(2)96周时,Zinbryta治疗组有73%的患者无复发,Avonex治疗组患者比例为59%,数据具有统计学显著差异(p<0.0001);(3)与Avonex相比,Zinbryta使多发性硬化症机体影响方面有意义的恶化风险(MSIS-29量表机体得分>7.5)降低24%(p=0.018);(4)根据扩展残疾状态量表(EDSS)测定的3个月确证残疾进展风险,与Avonex相比,Zinbryta降低16%,无统计学显著差异(p=0.016)。

高产工艺Zinbryta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。daclizumab是一种新型人源化单抗,结合T细胞表面的受体亚基CD25。多发性硬化症(MS)患者中,CD25呈高水平表达,T细胞被异常激活。daclizumab能够调节IL-2信号通路,而不会引起免疫细胞的消耗。

T细胞据信在诸如多发性硬化症(MS)等自身免疫疾病中异常激活。daclizumab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,能够靶向作用于在多发性硬化症(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)

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英文原文:Detailed Results from Biogen Idec and AbbVie's Pivotal Phase 3 Decide Study Further Define the Efficacy and Safety Profile of ZINBRYTA™ (Daclizumab High-Yield Process)

− Data Confirm ZINBRYTA™ is Superior to AVONEX® in Reducing Annualized Relapse Rate –

− First Presentation of Full DECIDE Results at ACTRIMS-ECTRIMS Meeting –

Today Biogen Idec (BIIB) and AbbVie (ABBV) announced the full results from the Phase 3 DECIDE clinical trial, which show ZINBRYTA™ (daclizumab high-yield process), dosed subcutaneously once a month, demonstrated a statistically significant improvement in reducing disease activity in people with relapsing-remitting multiple sclerosis (RRMS) compared to AVONEX®(interferon beta-1a).

These results are being presented at the Sixth Triennial Joint Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis and the European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS) in Boston.

"The full results from DECIDE demonstrate that ZINBRYTA significantly improved key measures of multiple sclerosis disease activity compared to AVONEX, including reducing annualized relapse rate and new brain lesion development," said Ludwig Kappos, M.D., chair, Department of Neurology and head, MS-Research Group, University Hospital, Basel, Switzerland, and lead investigator for DECIDE. "These results help us better understand ZINBRYTA as a potential treatment option for people with relapsing-remitting MS."

DECIDE Detailed Efficacy Results

DECIDE was a two- to three-year, Phase 3, global, randomized, double-blind study that evaluated whether ZINBRYTA would provide superior outcomes for certain clinical endpoints compared to AVONEX. The study enrolled more than 1,800 patients with RRMS.

Primary Endpoint:

Patients on ZINBRYTA demonstrated a statistically significant 45 percent reduction in annualized relapse rate (ARR) compared to patients treated with AVONEX (p<0.0001).

Secondary Endpoints:

ZINBRYTA demonstrated superiority in reducing the number of new or newly enlarging T2-hyperintense lesions at week 96, with a 54 percent reduction relative to AVONEX (p<0.0001).

The risk of three-month confirmed disability progression, as measured by the Expanded Disability Status Scale (EDSS), was reduced by 16 percent in patients treated with ZINBRYTA compared to those on AVONEX (p=0.16). This was not statistically significant.

Seventy-three percent of ZINBRYTA patients were relapse-free compared to 59 percent of AVONEX patients (nominal p<0.0001) at week 96.

The risk of meaningful worsening in the physical impact of multiple sclerosis (MS) (> 7.5 point worsening in the Multiple Sclerosis Impact Scale [MSIS-29] physical score) was reduced by 24 percent in the ZINBRYTA group compared to the AVONEX group (nominal p=0.018).

"For people living with multiple sclerosis, there continues to be a need for new medicines that work in different ways," said Gilmore O'Neill, vice president, Multiple Sclerosis Research and Development, Biogen Idec. "If approved, ZINBRYTA would offer a novel mechanism to treating MS, in a self-administered, once-monthly dosing regimen."

DECIDE Safety Results

The safety profile of ZINBRYTA in the DECIDE study was generally consistent with the Phase 2 studies. The overall incidence of adverse events was comparable across the ZINBRYTA and AVONEX treatment groups.

In patients treated with ZINBRYTA compared to AVONEX, there was an increased incidence of serious infections (4 percent vs. 2 percent). The pattern and types of infections seen in the ZINBRYTA group were consistent with what has been previously observed in the MS population.

Also consistent with previous studies, patients in the ZINBRYTA group had a greater incidence of cutaneous adverse events (37 percent vs. 19 percent) and serious cutaneous reactions (2 percent vs. < 1 percent); and elevations of liver transaminases greater than five times the upper limit of normal (6 percent vs. 3 percent). There were four deaths in the AVONEX group and one death in the ZINBRYTA group, none of which was considered treatment related.

Based on the efficacy and safety data from the ZINBRYTA clinical development program, Biogen Idec and AbbVie plan to file marketing applications for ZINBRYTA with regulatory authorities during the first half of 2015.

"The results from DECIDE further support the potential of ZINBRYTA and we look forward to submitting the data for this investigational therapy to regulatory agencies," said Michael Severino, M.D., executive vice president, Research and Development and chief scientific officer, AbbVie.

ZINBRYTA data will be presented:

Friday, Sept. 12 at 8:15 a.m. ET, Platform Presentation: Primary Results of DECIDE: A Randomized, Double-Blind, Double-Dummy, Active-Controlled Trial of Daclizumab HYP vs. Interferon β-1a in RRMS Patients (FC1.1)

Additional ZINBRYTA data were presented:

Thursday, Sept. 11 at 3:30 p.m. ET, Poster Presentation: Brain MRI Results of DECIDE: A Randomized, Double-Blind Trial of DAC HYP vs. IFNβ-1a in RRMS Patients (P051)

Thursday, Sept. 11 at 3:30 p.m. ET, Poster Presentation: Safety and Tolerability of Daclizumab HYP Treatment in Relapsing-Remitting Multiple Sclerosis: Results of the DECIDE Study (P094)

About DECIDE

DECIDE was a two- to three-year, Phase 3, global, randomized, double-blind, multicenter study designed to determine if ZINBRYTA would provide superior outcomes for certain clinical endpoints compared to treatment with AVONEX. The study enrolled more than 1,800 patients with RRMS in 28 countries. DECIDE was an active comparator study with two groups: 150 mg of subcutaneous ZINBRYTA every four weeks was compared to AVONEX 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). Secondary endpoints were rank ordered and tested with a sequential closed testing procedure to control inflation of type I error due to multiple endpoints. If a comparison was not statistically significant, then all endpoints of a lower rank were not significant per the closed testing procedure.

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

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

About ZINBRYTA™ (daclizumab high-yield process)

ZINBRYTA (daclizumab high-yield process) is an investigational drug and is a new form of a humanized monoclonal antibody that selectively binds to the high-affinity interleukin-2 (IL-2) receptor subunit (CD25) that is expressed at high levels on T-cells that become abnormally activated in MS. ZINBRYTA modulates IL-2 signaling without causing general immune cell depletion. ZINBRYTA 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 ZINBRYTA.

About AVONEX® (interferon beta-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.

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