2012年5月1日，辉瑞公司与Protalix生物治疗公司宣布，美国食品药品管理局(FDA)已批准Elelyso(taliglucerase alfa)——一种可注射给药的酶替代治疗(ERT)——用于确诊为1型戈谢病的成年患者的长期治疗。这是一种植物性药物，通过Protalix公司拥有专利的ProCellEx制造系统，由经过基因工程改造的胡萝卜细胞生产而成。Elelyso是一种人源化的溶酶体酶——葡糖脑苷酯酶。
Elelyso的获批是基于Protalix公司的临床研发数据。在一项招募了31例ERT初治的成年1型戈谢病患者的研究中，Elelyso的安全性和有效性得到了证实。这是一项为期9个月的多中心、双盲、随机试验，受试患者均有戈谢病相关性脾大和血小板减少。受试患者被随机分组，接受Elelyso 30 U/kg(n=15)或60 U/kg(n=16)治疗。该试验达到了其主要终点。9个月后，两组患者的脾脏体积均比基线时明显减小，肝脏体积、血红蛋白和血小板水平也有改善。
26例患者在该研究延长阶段继续在单盲状态下接受Elelyso治疗，共治疗24个月。结果显示临床指标继续改善。
在一项纳入25例由伊米苷酶转为Elelyso治疗的1型戈谢病患者的研究中，Elelyso的安全性和有效性也得到了评估。这是一项为期9个月的多中心、开放性、单组研究。受试患者基线时正在接受伊米苷酶治疗，剂量为11~60 U/kg不等，至少已治疗2年。停用伊米苷酶而给予Elelyso治疗，每2周给药1次，剂量与每例患者此前使用伊米苷酶的剂量一致。结果显示，在9个月Elelyso治疗过程中，器官体积和血液学指标维持稳定。
临床研究中报告的最常见不良反应为输液反应。观察到的最常见输液反应症状为头痛、胸痛或不适、无力、疲乏、荨麻疹、红斑、血压升高、背痛和关节痛，以及面部潮红。这些反应多为轻度而不需要治疗干预。其他的常见不良反应(发生率＜10%)为鼻咽炎、咽炎、头痛、关节痛、流感、肾盂肾炎、背痛和手足痛。
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:
6/18/2012
ELELYSO is a plant cell-expressed form of the glucocerebrosidase (GCD) enzyme. On May 1, 2012, Protalix and Pfizer announced that the U.S. Food and Drug Administration granted approval for ELELYSO as 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.
Learn more at ELELYSO.com
Important Safety Information for ELELYSO
As with any intravenous protein medicine, like enzyme replacement therapy (ERT), severe allergic reactions (including anaphylaxis) have been observed in patients treated with ELELYSO. If this occurs, your doctor may immediately discontinue ELELYSO. Patients who have experienced anaphylaxis to ELELYSO or another ERT should proceed with caution upon retreatment.
In addition, infusion reactions (including allergic reactions) – defined as a reaction occuring within 24 hours of the infusion -- were the most commonly observed reactions to ELELYSO. The most commonly observed infusion reactions were headache, chest pain or discomfort, weakness, fatigue, hives, abnormal redness of the skin, increased blood pressure, back or joint pain, and flushing. Most of these reactions were mild and did not require treatment.
Management of infusion reactions is based on the type and severity of the reaction. Your doctor may manage infusion reactions by temporarily stopping the infusion, slowing the infusion rate, or treating with medications such as an antihistamine and/or a fever reducer. Treatment with antihistamines and/or corticosteroids prior to infusion with ELELYSO may prevent these reactions.
Other common adverse reactions observed were upper respiratory tract infections, throat infection, flu, urinary tract infection, and pain in extremities.
As with all therapeutic proteins, including ERTs, there is a possibility of developing antibodies to ELELYSO. However, it is currently unclear whether this has an impact on the clinical response or adverse reactions. Patients with an immune response to other ERTs who are switching to ELELYSO should continue to be monitored for antibodies. Comparison of the frequency of antibodies across ERTs may be misleading.
If you are pregnant, or plan to become pregnant, you should talk to your doctor about potential benefits and risks.