今日，Sobi和Novimmune SA公司联合宣布，美国FDA批准双方共同开发的干扰素γ（IFNγ）抗体Gamifant（emapalumab-lzsg）上市，用于治疗儿童或成年原发性噬血细胞淋巴组织细胞增多症（HLH）患者。这些患者患有复发/难治性疾病，在接受常规HLH疗法后疾病继续恶化，或对常规疗法不耐受。Gamifant是FDA批准的首例针对HLH的疗法，这代表着治疗原发性HLH领域24年来的首个重大突破。
原发性HLH是一种非常罕见，进展迅速，通常致命的高度炎症性综合征。INFγ的大规模过度表达被认为是导致免疫系统过分激活的主要原因，这最终会导致器官衰竭。原发性HLH患者的症状通常在出生后第一年就会出现，如果不加以治疗，患者的平均生存期不到两个月。前期治疗的目标是尽快控制住高度炎症的紧急状况，为患者进行造血干细胞移植（HSCT）做准备。HSCT是目前唯一治愈HLH的方法。目前在接受HSCT之前的常规疗法是使用类固醇或者化疗，但是这些疗法都不是针对HLH的获批疗法。
Gamifant是一种IFNγ的单克隆抗体。它能够与IFNγ结合并且中和它的作用。该药物已经获得FDA授予的突破性疗法认定和孤儿药资格，而且新药申请也获得了优先审评资格。Gamifant获得批准与类固醇疗法地塞米松（dexamethasone）联用，每周两次通过静脉滴注给药，直到患者接受HSCT。
这项批准是基于Gamifant在一项全球性，多中心，开放标签，单臂关键性2/3期临床试验中的表现。在这项试验中，27名原发性HLH患者接受了Gamifant和地塞米松的联合治疗。这些患者对常规疗法没有响应，响应不佳或者不耐受。试验结果表明，Gamifant达到了试验的主要终点，在接受治疗6个月后，患者的总缓解率达到63%（p=0.013）。而且，70%的患者继续接受了HSCT。
“HLH是一种免疫调节异常疾病，虽然很多细胞因子水平都出现失常，但是IFNγ在疾病发生中起到关键性作用。很久以来，虽然我们知道这一细胞因子在HLH中的关键性作用，但是在emapalumab获得批准以前，我们没有一款药物能够特异性打击这一靶点，”emapalumab临床研究的首席研究员，辛辛那提儿童医院医疗中心HLH卓越中心的Michael Jordan博士说：“Emapalumab代表着治疗原发性HLH的一种全新方法，它将帮助这些重病患者达到接受造血干细胞移植的阶段。”
“Gamifant是第一款有针对性地靶向并中和IFNγ的药物。基于对这一新靶点的临床验证，我们将进行更多临床试验，检验emapalumab在其它因IFNγ导致的疾病中的疗效。我们非常感谢参与这项临床试验的患者，他们的家属和医护人员，是他们的努力让今天的批准成为可能。”Novimmune公司首席医学官Cristina de Min博士说。 
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
GAMIFANT safely and effectively. See full prescribing information for
GAMIFANT.
GAMIFANTTM (emapalumab-lzsg) injection, for intravenous use
Initial U.S. Approval: 2018
INDICATIONS AND USAGE
GAMIFANT is an interferon gamma (IFNγ) blocking antibody indicated forthe treatment of adult and pediatric (newborn and older) patients with primary
hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent orprogressive disease or intolerance with conventional HLH therapy. (1)
DOSAGE AND ADMINISTRATION
For intravenous infusion only:
Recommended starting dosage: 1 mg/kg as an intravenous infusion over 1hour twice per week. (2.1)
Administer dexamethasone concomitantly with GAMIFANT. (2.3)
DOSAGE FORMS AND STRENGTHS
Injection:
10 mg/2 mL (5 mg/mL) solution in a single-dose vial (3)
50 mg/10 mL (5 mg/mL) solution in a single-dose vial (3)

CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
Infections: Monitor patients for signs and symptoms and treat promptly.
Test for latent tuberculosis. Administer prophylactic treatment againstHerpes Zoster, Pneumocystis jirovecii and fungal infections. (5.1)
Live Vaccines: Do not administer live or live attenuated vaccines topatients receiving GAMIFANT. (5.2)
Infusion-Related Reactions: Monitor patients for infusion-relatedreactions. Interrupt infusion for severe infusion reactions and instituteappropriate medical management. (5.3)
ADVERSE REACTIONS
The most common adverse reactions (≥ 20%) were: infections, hypertensioninfusion-related reactions, and pyrexia. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact 1-866-773-5274 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION
Revised: 11/2018
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FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing
2.2 Monitoring to Assess Safety
2.3 Pre-Medications and Concomitant Medication Information
2.4 Dose Modification Based on Response
2.5 Instructions for Preparation and Administration
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Infections
5.2 Increased Risk of Infection with Use of Live Vaccines
5.3 Infusion-Related Reactions
6 ADVERSE REACTIONS
6.1 Clinical Trial Experience
6.2 Immunogenicity
7 DRUG INTERACTIONS
7.1 Effect of GAMIFANT on Cytochrome P450 Substrates
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information
are not listed.
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FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
GAMIFANT is indicated for the treatment of adult and pediatric (newborn and older) patientswith primary hemophagocytic lympho