当前位置：药品说明书与价格首页 >> 罕见病治疗药物 >> 新药动态 >> 欧盟批准Kanuma（sebelipase alfa）首款治疗LAL-D患者

欧盟批准Kanuma（sebelipase alfa）首款治疗LAL-D患者

2015-10-29 01:28:13 作者：新特药房来源：互联网浏览次数：0 文字大小：【大】【中】【小】

简介： 2015年7月，亚力兄制药宣布，欧盟委员会已批准Kanuma（sebelipase alfa）在所有年龄的溶酶体酸脂酶缺乏（LAL-D）患者中用于长期的酶替代治疗（ERT）。 Kanuma是一种新型ERT，它是欧盟批准的首款用于LAL-D ...

关键字：sebelipase alfa商品名Kanuma 首款用于罕见代谢性疾病

2015年7月，亚力兄制药宣布，欧盟委员会已批准Kanuma（sebelipase alfa）在所有年龄的溶酶体酸脂酶缺乏（LAL-D）患者中用于长期的酶替代治疗（ERT）。
Kanuma是一种新型ERT，它是欧盟批准的首款用于LAL-D患者的治疗药物，LAL-D是一种遗传性、进展性的极其罕见代谢性疾病，患有此病的患者会遭受多器官损伤及过早死亡。亚力兄制药预计于10月份在德国开始为患者提供这款药物，目前该公司正与主要欧盟国家的医保机构商谈报销程序。
今天的批准对LAL-D患者来说是一个重要的里程碑，这种严重疾病可能对所有年龄的患者导致灾难性的后果，Kanuma 关键研究的研究者、医学博士、哲学博士 Valayannopoulos 称。
在临床研究中，67%的以Kanuma治疗的婴儿活过了1岁，但如果没有这种治疗，这些患者可能会面临几乎可以肯定的致命后果。在儿科及成年患者中，Kanuma也显示能够降低肝损伤标志物及脂质积聚，脂质积聚可导致严重及危及生命的并发症。
LAL-D是一种遗传性、慢性及进展性的代谢疾病，患有该病的婴儿、儿童及成年人会遭受多种器官的损伤及过早死亡。这是一种极其罕见的疾病，这种病在每100万普通人群中的发病人数不会超过。
LAL-D患者通常会经历危及生命疾病临床体征的发作，其类似于其它的肝脏疾病，许多患者在经历该疾病的一种严重后果之前可能是无症状的。LAL-D由基因突变引起，这种基因突变会导致多种人体组织溶酶体中LAL酶活性降低或丧失，从而导致胆固醇酯和甘油三酯在肝脏、血管壁及其它组织内的长期积聚。
我们非常高兴欧盟委员会批准 Kanuma 用于所有年龄的LAL-D患者，这可以让我们用这款首次获批用于这种极其罕见、严重及危及生命疾病的治疗药物来拯救欧洲的婴儿、儿童及成年患者，亚力兄制药首席执行官Hallal称。
如果没有任何有效药物治疗，LAL-D患者将面临灾难性的病状，包括肝衰竭及过早死亡。我们感谢研究者、患者及他们参与到临床试验的家人，这使得该药物的获批成为可能，我们现在正与整个欧洲的医保机构讨论报销程序，以确保LAL-D患者可以尽快获得Kanuma这样一款改变生命的治疗药物。
Kanuma是一种高度创新性的酶替代疗法（ERT），它旨在解决LAL-D的病因。Kanuma 的批准施用于所有28个欧盟成员国，以及爱尔兰、挪威及列支敦士登，这款药物是在加速审评程序下获得批准的。
在此之前，人用医药产品委员会（CHMP）对这款药物给予了积极的意见。此外，美国 FDA授予Kanuma治疗LAL缺乏婴儿患者突破性治疗药物资格，FDA还授予Kanuma的生物制剂许可申请优先审评资格。
New Drugs Online Report for sebelipase alfa
Information
Generic Name: sebelipase alfa
Trade Name: Kanuma
Synonym: SBC 102
Entry Type: New molecular entity
Development and Regulatory status
UK: Launched
EU: Launched
US: Pre-registration (Filed)
UK launch Plans: Available only to registered users
Actual UK launch date: September 2015
Comments
Sep 15: Launched in UK, available for order from Alexion Pharma UK only [19].
05/10/2015 14:12:27
Sep 15: FDA delays its decision by another 3 months in order to examine some requested additional information on manufacturing of sebelipase [17].
07/09/2015 10:06:38
Sep 15: Approved in EU [16].
03/09/2015 12:34:36
Jun 15: EU positive opinion for long-term enzyme replacement therapy in patients of all ages with LAL deficiency [15].
26/06/2015 12:21:10
May 15: Alexion is to buy Synageva, with the deal expected to complete by mid-2015 [14].
07/05/2015 14:02:01
Feb 15: The FDA has granted the company′s request for Priority Review and target action date of September 8, 2015 under the Prescription Drug User Fee Act (PDUFA) set. [12]
24/02/2015 09:57:50
Dec 14: Company annouced submission of a Marketing Authorization Application (MAA) in the EU for sebelipase alfa for LAL Deficiency, which is subject to the validation process by the European Medicines Agency (EMA). The EMA recently granted the company′s request for accelerated assessment, which has the potential to shorten the EMA′s regulatory review time [11].
03/12/2014 09:53:01
Oct 14: FDA receives rolling submission of licensing application for sebelipase alfa for treatment of patients with lysosomal acid lipase deficiency. EU application expected to be filed by end Jan 15 [9].
27/10/2014 10:37:25
May 13: Granted ′breakthrough therapy′ status in the US for treatment of lysosomal acid lipase deficiency [6].
21/05/2013 08:42:03
Jun 11: Granted fast track status in the US [2].
27/06/2011 17:39:24
June 11: Orphan drug designation in US and EU. [1]
23/06/2011 16:52:34
Trial or other data
While its pricing strategy has not yet been revealed, according to a Barclays analyst, it will be priced at around $375,000 a year [16].
28/09/2015 16:38:30
Sep 15: Results of PIII trial (NCT01757184), published in NEJM, found that at 20 weeks, alanine aminotransferase level was normal in 11 of 36 patients (31%) in sebelipase alfa group and in 2 of 30 (7%) in placebo group (p=0.03), with mean changes from baseline of ?58 U/L vs. ?7 U/L, respectively (p<0.001) [18].
16/09/2015 12:57:53
Nov 14: Positive top line data reported from PIII study of sebelipase alfa in 66 pts aged 4-58 with LAL deficiency. Pts received infusions of sebelipase alfa (1 mg/kg) or placebo every other week for 20 wks. in double-blind treatment period. Primary endpoint, normalisation of ALT (to 34-43 U/L) was met by 31% (11/36) of sebelipase alfa pts and 7% (2/30) of placebo pts (p=0.027). ALT decreased in all pts on sebelipase alfa vs placebo; -57.9 U/L vs. -6.7 U/L. Significant improvements in multiple disease-related parameters of dyslipidemia and liver injury were noted (e.g. reduction in hepatic fat fraction -32% vs. -4% [p<0.001]). Overall incidence of ADRs were similar for both groups with some ADRs more common in sebelipase alfa treated patients; headache (28% vs. 20%), pyrexia (25% vs. 23%), oropharyngeal pain (17% vs. 3%), nasopharyngitis (11% vs. 10%), abdominal pain (8% vs. 3%), constipation (8% vs. 3%), nausea (8% vs. 7%) and asthenia (8% vs. 3%) [10].
12/11/2014 13:01:12
Jan 14: The company has met the enrolment target (n=9) in the multicentre, open-label PII/III trial in infants with LAL Deficiency. Infants with growth failure before six months of age were eligible to enrol and receive weekly infusions with sebelipase alfa. The primary endpoint is survival at 12 months of age. Preliminary results will be presented at the LDN WORLD Symposium in Feb 14 [8]
07/01/2014 10:30:12
Dec 13: Enrollment (n=50) in ARISE completed. Top-line results will be available H2 2014 [7]
05/12/2013 13:15:39
May 13: 12-month results from an ongoing extension study with sebelipase alfa in adults with late onset Lysosomal Acid Lipase (LAL) Deficiency reported. Of 9 adults enrolled in the P1/2 trial, 8 continued treatment and 6 have completed the first 12 months of the study. Sebelipase alfa was generally well tolerated. The majority of AEs were gastrointestinal (diarrhoea, abdominal cramping) events of mild severity. One patient with a moderate (Grade 2) allergic type infusion-related reaction, who paused treatment 9 nine months remains off treatment with further tests pending. No anti-drug antibodies have been detected in any subjects tested. One patient developed acute cholecystitis and cholelithiasis which were treated with elective cholecystectomy. These two serious Aes were considered unlikely related to sebelipase alfa. This patient continues treatment with sebelipase alfa without a change in dosing and administration [5].
13/05/2013 09:37:48
Feb 13: First patient initiated treatment in the ARISE trial (Acid Lipase Replacement Investigating Safety and Efficacy), a global, Phase 3, randomised, double-blind, placebo-controlled study of sebelipase alfa in children and adults with late onset lysosomal acid lipase deficiency (LAL Deficiency). [4]
12/02/2013 09:11:00
Sep 11: Synageva BioPharma has announced it has expanded its ongoing global study of SBC 102 for infants with LAL deficiency to the US [3].
29/09/2011 09:39:03
Jun 11: SBC 102 is a recombinant human lysosomal acid lipase. This enzyme is responsible for the breakdown of cholesteryl esters and triglycerides. Late onset LAL deficiency, also called Cholesteryl Ester Storage Disease (CESD), affects both children and adults. In these patients, the build up of fatty material in the liver, spleen and blood vessel walls leads to complications resulting in significant morbidity and mortality. Early onset LAL deficiency, sometimes called Wolman Disease, causes growth failure in infants and almost always results in death in the first year of life. [1]
23/06/2011 16:52:04
Evidence Based Evaluations
NICE scope http://www.nice.org.uk/guidance/indevelopment/gid-lysosomalacidlipasedeficiencysebelipasealfaid737
EPAR http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004004/WC500192717.pdf
NHSC/NIHR http://www.hsc.nihr.ac.uk/topics/sebelipase-alfa-for-lysosomal-acid-lipase-deficien/
References
Available only to registered users
Category
BNF Category: Drugs used in metabolic disorders (09.08.01)
Pharmacology: recombinant human lysosomal acid lipase
Epidemiology: lysosomal acid lipase deficiency affects <0.2 in 10,000 people in the EU, equivalent to a total of fewer than 10,000 people
Indication: Lysosomal acid lipase deficiency
Method(s) of Administration
Intracerebral
Intravenous
Company Information
Name: Synageva BioPharma
US Name: Synageva BioPharma
Further Information
Anticipated commissioning route (England) NHSE
High cost drug list? Yes
Tariff Not routinely commissioned by NHSE - IFR approval [13]
In NICE timetable: Yes
When: Jun / 2016
Note: www.nice.org.uk/guidance/indevelopment?type=hst
Implications Available only to registered users