Lumizyme Approved for Late-Onset Pompe Disease

Emma Hitt, PhD

May 27, 2010

May 27, 2010 (UPDATED JUNE 3, 2010) — The US Food and Drug Administration (FDA) has approved alglucosidase alfa (Lumizyme; Genzyme) for the treatment of late-onset Pompe disease in patients 8 years and older.

Alglucosidase alfa supplements levels of α-glucosidase, the enzyme deficient in Pompe disease, thereby decreasing the accumulation of glycogen in heart and muscle cells. To ensure its appropriate use, this agent is being approved with a risk evaluation and mitigation strategy and will be available only through a restricted distribution system called the Lumizyme ACE (Alglucosidase Alfa Control and Education) Program.

The new approval is based on a clinical study in 90 patients with late-onset Pompe disease aged 10 to 70 years. The most commonly reported adverse effects (≥ 5%) were infusion-related reactions, including severe allergic reactions, hives, diarrhea, vomiting, shortness of breath, itchy skin, rash, neck pain, partial hearing loss, flushing, pain in the extremities, and chest discomfort. The prescribing information for alglucosidase alfa carries a boxed warning describing the risk for anaphylaxis, severe allergic reactions, and immune-mediated reactions.

Myozyme, another form of alglucosidase alfa also manufactured by Genzyme, is approved for the treatment of Pompe disease; however, this agent has been in short supply because of limitations in the manufacturing process. Myozyme is currently reserved for treating infants and children, who have a more aggressive form of Pompe disease than that occurring in older children and adults.

"Pompe disease is a devastating condition without the appropriate treatment," noted Julie Beitz, MD, director of the Office of Drug Evaluation III in the FDA's Center for Drug Evaluation and Research, in a written release. "The approval of Lumizyme will provide an important treatment for patients diagnosed later in life with Pompe disease," she stated.

Pompe disease occurs in an estimated 1 in every 40,000 to 300,000 births. Its primary symptom is heart and skeletal muscle weakness, progressing to respiratory weakness and death from respiratory failure.

In November 2009, Myozyme and other products manufactured by Genzyme were linked to reports of contamination with stainless steel particles. For more information, see

Adverse events related to these products should be communicated to MedWatch by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

Dosing Recommendations

The recommended dosage of 5-mg/mL alglucosidase alfa solution is 20 mg/kg body weight, administered biweekly via intravenous infusion pump for approximately 4 hours.

The initial infusion should be 1 mg/kg/hour or less. The infusion rate may be increased in a stepwise manner by 2 mg/kg/hour every 30 minutes to a maximum of 7 mg/kg/hour based on patient tolerance. Vital signs should be obtained at the end of each step, and the infusion rate should be slowed or temporarily stopped for infusion reactions.

Because alglucosidase alfa reconstituted solution does not contain any preservatives, unused portions should be discarded.

Use in Special Populations

Reproduction studies performed in pregnant mice and rabbits given intravenous doses of up to 40 mg/kg/day have revealed no evidence of impaired fertility or fetal harm (total plasma exposure area under the curve, 64.6 and 85 mg∙minute/mL, 0.4 and 0.5 times the human steady-state exposure at the recommended biweekly dose, respectively).

However, there have been no adequate and well-controlled studies in pregnant women, and animal study findings do not always correlate with human response. Therefore, alglucosidase alfa should only be used during pregnancy if clearly needed. Because many drugs are secreted in human milk, caution is advised when treating nursing mothers.

Women of childbearing potential, pregnant women, and nursing mothers should be encouraged to enroll in the Pompe Registry, which has been established to better understand disease variability and progression as well as monitor the long-term effects of alglucosidase alfa on pregnant women and their children.

Alglucosidase alfa is not indicated for use in patients younger than 8 years with infantile-onset or late-onset Pompe disease. Although the randomized, double-blind, placebo-controlled safety and efficacy study submitted to the FDA as a basis for product approval was designed to enroll 90 patients aged 8 to 70 years, the youngest alglucosidase alfa–treated patient was 16 years old, and the youngest to receive placebo was 10 years old.

Descriptive clinical data from 15 patients with infantile-onset Pompe disease who received treatment outside the United States were collected in the Pompe Registry and were used to verify the product's overall efficacy in patients 8 years and older with late-onset disease.

The study also included only 4 patients 65 years and older, a number insufficient to determine whether elderly patients respond differently to alglucosidase alfa than their younger counterparts.

Yael Waknine Weiss contributed to the news article.


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