美国食品和药物管理局批准Lumizyme（algucosidase且阿尔法）患者年龄为8岁及以上的晚发性（非婴儿）庞贝氏症，一种罕见的遗传性疾病。

庞倍氏症（Pompe），又称2型糖原累积症，是一种罕见的严重肌体衰弱性疾病。该病最终会因人体呼吸功能衰竭而导致死亡，对新生儿的危害尤其严重。目前在美国，患庞倍氏症的患者达4万~30万人。
Lumizyme--治疗庞倍氏症（Pompe）新药

Lumizyme approved for Pompe disease

Genzyme announced the FDA approval of Lumizyme (alglucosidase alfa), a lysosomal glycogen-specific enzyme, for the treatment of patients ≥8 years of age with late (non-infantile) onset Pompe disease (acid α-glucosidase (GAA) deficiency) who do not have evidence of cardiac hypertrophy. Lumizyme is administered to patients intravenously every two weeks. This approval was based on data from a randomized double-blind, placebo-controlled clinical study in 90 patients (ages 10–70 years) with late-onset Pompe disease.

Lumizyme will be available only through a restricted distribution program called the Lumizyme ACE Program. Only prescribers and healthcare facilities enrolled in the program may prescribe, dispense, or administer Lumizyme.

Genzyme Receives FDA Approval for Lumizyme for Pompe Disease

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Genzyme Corporation (Nasdaq: GENZ) announced today that the FDA has granted U.S. marketing approval for Lumizyme™ (alglucosidase alfa), produced at the 4000 liter (L) bioreactor scale at its manufacturing facility in Geel, Belgium. Lumizyme is the first treatment approved in the United States specifically to treat patients with late-onset Pompe disease.

“This is an important day for the Pompe community, especially for those patients with late-onset Pompe disease in the United States who are awaiting treatment for this devastating disease”

“This is an important day for the Pompe community, especially for those patients with late-onset Pompe disease in the United States who are awaiting treatment for this devastating disease,” said Genzyme Chairman and Chief Executive Officer, Henri A. Termeer. “We are grateful to the FDA for their efforts to approve Lumizyme ahead of its scheduled PDUFA date.”

Lumizyme (alglucosidase alfa) is a lysosomal glycogen-specific enzyme indicated for patients 8 years and older with late (non-infantile) onset Pompe disease (GAA deficiency) who do not have evidence of cardiac hypertrophy. The safety and efficacy of Lumizyme have not been evaluated in controlled clinical trials in infantile-onset patients, or in late (non-infantile) onset patients less than 8 years of age.

Genzyme began work on a therapy for Pompe disease ten years ago, and the company has invested nearly $1 billion to support the development program. In 2006, Genzyme received approval for Myozyme® (alglucosidase alfa) in Europe and in other countries outside of the United States manufactured at a 2000 L bioreactor scale and indicated to treat all patients with Pompe disease. At this time, Genzyme also received FDA approval for Myozyme manufactured at a smaller 160 L bioreactor scale in the United States, which, because of its limited capacity, has been reserved for children and infants in the United States. In 2009, Genzyme received approval outside of the United States for manufacturing Myozyme in 4000 L bioreactors at its state-of-the-art manufacturing facility in Geel, Belgium, and began to transition patients globally to the product manufactured at this larger scale. To prepare for growing demand for alglucosidase alfa, Genzyme has installed a third 4000 L bioreactor in Geel with an anticipated approval in 2011.

Genzyme has worked closely with patients and physicians in the U.S. Pompe community during the preapproval period to assure that the most severely affected late-onset patients could access therapy in advance of Lumizyme approval. In May 2007, Genzyme began providing alglucosidase alfa free-of-charge to patients in the United States through a program known as the Alglucosidase Alfa Temporary Access Program (ATAP). Nearly 200 severely affected adults in the United States with Pompe disease are currently receiving treatment under the ATAP program. Genzyme will now work closely with the treating centers and prescribers to insure that patients in the ATAP program can continue to access therapy during the transition to commercial supply. Genzyme will also begin working with U.S. healthcare professionals to help adult patients who have been waiting to access treatment. In effort to preserve 160-L scale product for infantile-onset patients, Genzyme will begin to transition eligible patients who are receiving Myozyme onto Lumizyme.

Because Genzyme will market two approved alglucosidase alfa products in the United States, a Risk Evaluation and Mitigation Strategy called the Lumizyme ACE (alglucosidase alfa control and education) Program will be implemented for Lumizyme to ensure appropriate use for the intended patient populations. All prescribers of Lumizyme, and healthcare facilities where Lumizyme will be dispensed and administered, are required to be certified and enrolled in the Lumizyme ACE Program prior to treating patients with Lumizyme. Prescribers must also ensure patients enroll in the Lumizyme program prior to receiving therapy. Genzyme will begin this process immediately to certify and enroll prescribers and healthcare facilities and to help prescribers to enroll all patients that they intend to treat with Lumizyme.

About Pompe Disease

Pompe Disease is a progressively debilitating disease that manifests as a broad spectrum of clinical symptoms. All patients typically experience progressive muscle weakness and breathing difficulty, but the rate of disease progression can vary widely depending on the age of onset and the extent of organ involvement. When symptoms appear within a few months of birth, babies frequently display a markedly enlarged heart and die within the first year of life. When symptoms appear during childhood, adolescence or adulthood, patients may experience steadily progressive debilitation and premature mortality due to respiratory failure. They often require mechanical ventilation to assist with breathing and wheelchairs to assist with mobility.

Important Safety Information about Lumizyme

Lumizyme has a boxed warning as follows: Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during Lumizyme infusions. Therefore, appropriate medical support should be readily available when Lumizyme is administered.

Because of the potential risk of rapid disease progression in Pompe disease patients less than 8 years of age, Lumizyme is available only through a restricted distribution program called the Lumizyme ACE Program. Only prescribers and healthcare facilities enrolled in the program may prescribe, dispense, or administer Lumizyme. Lumizyme may be administered only to patients who are enrolled in and meet all the conditions of the Lumizyme ACE Program. To enroll in the Lumizyme ACE Program call 1-800-745-4447.

Severe cutaneous reactions have been reported with alglucosidase alfa including necrotizing skin lesions. Systemic immune mediated reactions, including possible type III immune complex-mediated reactions have been observed with alglucosidase alfa. Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Other serious adverse events that occurred in a higher incidence in Lumizyme treated patients compared to placebo included coronary artery disease, intervertebral disc protrusion, pneumonia, gastroenteritis, and dehydration. The most common adverse reactions observed in clinical studies were infusion reactions. Those occurring in Lumizyme treated patients at an incidence of ≥ 5% compared to placebo included anaphylaxis, urticaria, diarrhea, vomiting, dyspnea, pruritus, rash/erythema, pharyngolaryngeal pain, neck pain, hypoacusis, flushing/feeling hot, pain in extremity, fall and chest discomfort.

In post-marketing experience with Lumizyme, deaths, and serious adverse reactions have been reported, including anaphylaxis. Adverse events resulting in death reported in the postmarketing setting with Lumizyme treatment included cardiorespiratory arrest, respiratory failure, hemothorax, pneumothorax, cardiac failure, sepsis, aortic dissection, cerebrovascular accident, and skin necrosis. The most frequently reported serious adverse reactions were infusion reactions. The following serious adverse events have been reported in at least 2 patients: dyspnea, respiratory failure, bronchospasm, stridor, decreased oxygen saturation/hypoxia, pharyngeal edema, chest discomfort, chest pain, hypotension, hypertension, erythema, flushing, lung infection, tachycardia, cyanosis, and hypersensitivity. One case of hyperparathyroidism has been reported.

庞倍氏症

心肌糖原沉积病[庞培氏(Pompe)病] 　　

心肌糖厚沉积病由Pompe(1932)提出，为糖原合成和分解代谢中所需一系列酶的缺陷所致病变，是一种先天性代谢病，本病罕见，是引起婴儿心脏迅速增大的疾病之一，亦即所谓特发性心脏肥大。 　
[病因] 　　

为糖原分解酶(如a-1，4-葡萄糖苷酶)的缺陷，不能分解为葡萄糖而造成糖原质和量的代谢障碍，使组织中的糖原累积，因此近年把这类疾患总称为糖原沉积病，由于受累的组织或器官不同，可区别为+或+ -型，绝大多数与常染色体隐性遗传有关。实际上可分为肝，心，肌肉三大类，如1型称为肝糖原沉积病（GSDI 亦称VonGierke病），2型为心肌糖原沉积病（GSDI，pampe病等）。3型即肌性糖原沉积病。 　

[病理] 　　

由于组织中糖原积累，造成器官的肿大与功能不全，如心脏明显增大，主要是心室壁增厚，左室可厚达30毫米（正常为7~10毫米）糖原代谢了肌纤维，并有空泡形成，退行性坏死，但无炎症改变，同时可累及肝，肾和有纹肌等。 　

[临床情况] 　　

1.病人出生后数周或数月发病，男女相等，病情发展快，常早年死于心力衰竭或呼吸道感染，但也有见于成人者。 　　

2.心脏明显增大但一般无杂音，肌肉软弱无力，巨舌，面容与呆小症或伸舌痴愚相似，肝脾肿大常不明显。 　　

3.胃纳差，呕吐，呼吸困难，紫绀，水肿以及营养不良，发育迟缓等表现。 　　

4.心电图左心肥厚，T波倒置，S~T段下降，血液检查末梢白细胞的酸性麦芽糖酶（葡萄糖苷酶）的活性显著降低。 　

[X线表现] 　　

1、心脏呈对称性的原形或球形明显扩大，主要是心室，不侵犯心房，搏动减弱，并可压迫左上支气管，引起左上叶肺不张，晚期有时合并肺郁血或肺炎的表现。 　　

2，心血管造影，显示左心室壁增厚，血液循环正常，有时左肺动脉压升高。 　　
[鉴别诊断] 　　应与心内膜弹力纤维增生症鉴别，二者X线表现大致相同，又可并存。其它如支气管肺炎伴心力衰竭，先天性心血管畸形，心肌炎等相区别。