2012年5月1日，FDA宣布批准长效酶替代疗法taliglucerase alfa（Elelyso）用于治疗罕见遗传疾病——戈谢病。
戈谢病患者体内无法产生足够的葡萄糖脑苷脂酶。该酶的不足导致脂肪物质积蓄在脾、肝、肾等器官内。戈谢病的主要体征为肝脏或脾脏损害、贫血、血小板低和骨骼问题。
Elelyso是酶替代注射剂，由专业医护人员每隔一周给予1型（非神经性）戈谢病患者。在美国，预计大约有6,000名1型戈谢病患者。
由于该病影响到的人群较小，Elelyso疗效的评价在2项总共包含56名1型戈谢病患者的临床研究中进行，多数患者继续参加了后续扩展临床研究。
一项多中心、双盲、平行研究评价了Elelyso作为初始治疗用于31名没有接受过酶替代疗法的患者的作用。患者随机接受30或60units/kg剂量的Elelyso。两种剂量的Elelyso都有效减小了病人的脾脏体积（研究的首要终点），经过9个月的治疗，和基线相比，给予30 units/kg Elelyso的病人脾脏平均减小了29%，给予60 units/kg Elelyso的病人脾脏平均减小了40%。
另一项研究评价了Elelyso用于25名之前使用另一种酶替代治疗产品imiglucerase for Injection（注射用伊米苷酶，思而赞，Cerezyme）患者的作用。在这项多中心、开放式、单组研究中，之前这些至少使用了2年的imiglucerase的患者开始每隔一周给予和imiglucerase相同剂量的Elelyso。结果显示Elelyso在9个月评价期中有效维持了脾脏、肝脏体积、血小板计数和血红蛋白水平。
Elelyso临床研究最常见的不良反应为输液反应和过敏反应。输液反应的症状包括头疼、胸痛或不适、虚弱、疲劳、荨麻疹、皮肤发红、血压升高、背部疼痛、关节疼痛和脸红。和其他的静脉蛋白产品一样、Elelyso输液也出现过过敏反应。
其他常见的不良反应（>10%）包括上呼吸道感染，感冒样症状（鼻咽炎）、关节疼痛、流行性感冒、头疼、肢体末端疼痛、背部疼痛和尿道感染。
Elelyso由美国辉瑞负责生产销售，辉瑞是从Protalix BioTherapeutics获得的许可权。
Manufacturer:
Pfizer Inc.
Pharmacological Class:
Lysosomal glucocerebroside-specific enzyme.
Active Ingredient(s):
Taliglucerase alfa (recombinant) 200 Units; per vial; lyophilized pwd; for IV infusion after reconstitution; preservative-free.
Indication(s):
Long-term enzyme replacement therapy (ERT) for adults with Type 1 Gaucher disease.
Pharmacology:
Elelyso catalyzes the hydrolysis of glucocerebroside to glucose and ceramide. In clinical trials, Elelyso reduced spleen and liver size, and improved anemia and thrombocytopenia.
Clinical Trials:
In Study 1, the safety and efficacy of Elelyso was assessed in a 9-month multi-center, double blind, randomized study in patients with Gaucher disease-related enlarged spleens (>8 times normal) and thrombocytopenia (<120,000 /mm3). Sixteen patients had enlarged livers and ten patients had anemia at baseline. All patients were naïve to ERT. Patients were randomized to receive Elelyso at a dose of either 30 Units/kg (n=15) or 60 Units/kg (n=16). At baseline, for the respective 30 Units/kg and 60 Units/kg dose groups, mean % body weight (%BW) and multiples of normal (MN) spleen volumes were 3.1 and 3.3 (%BW) and 15.4 and 16.7 (MN); liver volumes were 4.2 and 3.8 (%BW) and 1.7 and 1.5 (MN); hemoglobin concentrations were 12.2 and 11.4 g/dL and platelet counts were 75,320 and 65,038/mm3. At endpoint, the changes in clinical parameters after 9 months of treatment: mean (SD) spleen volume (%BW) were -0.9 (0.4) and -1.3 (1.1), (MN) were -4.5 (2.1) and -6.6 (5.4); mean hemoglobin were 1.6 (1.4) g/dL and 2.2 (1.4) g/dL; mean liver volume (%BW) were -0.6 (0.5) and -0.6 (0.4), (MN) were -0.2 (0.2) and -0.3 (0.2); mean platelet count were 11,427 (20,214) /mm3 and 41,494 (47,063)/mm3, for the 30 Units/kg and 60 Units/kg dose groups, respectively.
In Study 2, the safety and efficacy of Elelyso was assessed in 25 patients with Type 1 Gaucher disease who were switched from imiglucerase to Elelyso. The trial was a 9-month, multi-center, open-label, single arm study in patients who had been receiving treatment with imiglucerase at doses ranging from 11 Units/kg to 60 Units/kg for a minimum of 2 years. Patients also were required to be clinically stable and to have a stable biweekly dose of imiglucerase for at least 6 months prior to enrollment. Imiglucerase therapy was stopped, and treatment with Elelyso was given every other week at the same number of units as each patient’s previous imiglucerase dose. Organ volumes and hematologic values remained stable on average through 9 months of Elelyso treatment. At baseline, spleen volume (%BW) was 1.1% and (MN) was 5.5; liver volume (%BW) was 2.4% and (MN) was 1.0; mean hemoglobin was 13.6 (± 1.57) g/dL; and mean platelet count was 160,447 (± 79,086) /mm3. At endpoint, spleen volume (%BW) was 1.0% and (MN) was 5.1; liver volume (%BW) was 2.3% and (MN) was 0.9; mean hemoglobin was 13.4 (± 1.6) g/dL and mean platelet count was 165,654 (± 94,038) /mm3.
Study 3 includes patients continuing treatment from Study 1 and Study 2. Twenty-four patients were treated for longer than 2 years and 4 patients were treated for longer than 3 years.
Legal Classification:
Rx
Adults:
Give by IV infusion over 60–120 minutes. Individualize. 60 Units/kg once every 2 weeks. Begin treatment with Elelyso at the same dose when switching from imiglucerase.
Children:
Not established.
Warnings/Precautions:
Discontinue if anaphylaxis occurs and treat appropriately. Temporarily discontinue, decrease infusion rate, or administer antihistamines, corticosteroids and/or antipyretics if allergic or infusion reactions occur. Monitor for IgG antibody formation. Pregnancy (Cat.B). Nursing mothers.
Adverse Reaction(s):
Infusion or allergic reactions (eg, chest pain, discomfort, asthenia, fatigue, urticaria, erythema, increased blood pressure, back pain, flushing), URTI/nasopharyngitis, pharyngitis/throat infection, headache, arthralgia, influenza/flu, UTI/pyelonephritis, back pain, extremity pain.
How Supplied:
Single-use vials—1
Last Updated:
ELELYSO™ (taliglucerase alfa) for injection is supplied as 200 Units per vial and is available by prescription only.
INDICATION
ELELYSO™ (taliglucerase alfa) for injection is a hydrolytic lysosomal glucocerebroside-specific enzyme indicated for long-term enzyme replacement therapy (ERT) for adults with a confirmed diagnosis of Type 1 Gaucher disease.
IMPORTANT SAFETY INFORMATION
As with any intravenous protein product, severe allergic reactions are possible. Anaphylaxis has been observed in patients treated with ELELYSO. If anaphylaxis occurs, ELELYSO should be discontinued immediately, and appropriate medical treatment should be initiated.
In patients who have experienced anaphylaxis during infusion with ELELYSO or with other enzyme replacement therapies (ERTs), caution should be exercised upon retreatment; appropriate medical support should be readily available.
Infusion reactions (including allergic reactions), defined as a reaction occurring within 24 hours of the infusion, were the most commonly observed reactions in patients (44%-46%) treated with ELELYSO in clinical studies. The most commonly observed symptoms of infusion reactions were headache (16%), chest pain or discomfort (6%), asthenia (7%), fatigue (5%), urticaria (7%), erythema (5%), increased blood pressure (5%), back pain and arthralgia (7%), and flushing (6%). Most of these reactions were mild and did not require treatment intervention.
Base the management of allergic or infusion reactions on the type and severity of the reaction, eg, temporarily stopping the infusion and/or decreasing the infusion rate, and/or treating with medications such as antihistamines and/or antipyretics.
Pretreatment with antihistamines and/or corticosteroids may prevent subsequent reactions in those cases where symptomatic treatment was required. Patients were not routinely premedicated prior to infusion of ELELYSO during clinical studies.
Other commonly observed adverse reactions in ≥10% of patients were URTI/nasopharyngitis, pharyngitis/throat infection, influenza/flu, UTI/pyelonephritis, and extremity pain. One patient experienced a type III immune-mediated skin reaction (fixed drug eruption).
As with all therapeutic proteins, patients have developed IgG antidrug antibodies (ADA) to ELELYSO. The relevance of ADA to therapeutic response and adverse events is currently unclear.
It is unknown if the presence of ADA to ELELYSO is associated with a higher risk of infusion reactions. Patients who develop infusion or immune reactions with ELELYSO treatment should be monitored for ADA. Additionally, patients with an immune reaction to other ERTs who are switching to ELELYSO should be monitored for ADA to ELELYSO. Comparison of the incidence of antibodies across ERTs may be misleading.
