Major Finding: Patients who received active treatment showed a mean increase of 25.1 m on the walk test, whereas those who received placebo showed a decrease of 3.0 m, for a differential effect of 28.1 m. Those who received active treatment showed a increase of 1.2 percentage points in predicted FVC, while those who received placebo showed a decrease of 2.2 percentage points, for a differential effect of 3.4 percentage points.
Data Source: A randomized, controlled trial involving 90 patients with late-onset Pompe's disease.
Disclosures: Dr. van der Ploeg and most associates in this study reported receiving support from Genzyme. Some associates reported receiving support from numerous makers of drugs, devices, and technologies. The study was designed and funded by Genzyme Corp., maker of alglucosidase alfa.
Enzyme-replacement therapy with recombinant human alglucosidase alfa “has a positive, if modest, effect on walking distance and pulmonary function” in patients who have late-onset Pompe's disease, according to Dr. Ans T. van der Ploeg of Erasmus University, Rotterdam, the Netherlands, and associates.
Pompe's disease is a rare, autosomal recessive, progressive neuromuscular disorder caused by a deficiency of acid alpha-glucosidase, which leads to deposition of glycogen primarily in skeletal and respiratory muscles.
The late-onset form of the disease is characterized by limb-girdle myopathy and respiratory insufficiency that often eventually proves fatal.
Enzyme-replacement therapy using recombinant human alglucosidase alfa was approved for use in classic infantile-onset Pompe's disease in 2006.
Preliminary studies of the agent's use in children and adults who have the late-onset form of the disease showed “some positive effects,” but those studies were small and uncontrolled, the investigators wrote.
To address those shortcomings, the investigators conducted a randomized, controlled trial involving 90 patients with late-onset Pompe's disease, which is a large population for a clinical trial of an orphan disease but “relatively small when the goal is to judge the progression of a clinically heterogeneous” disorder.
The study subjects were between 10 and 70 years of age at enrollment, and all had developed symptoms while between 2 and 59 years of age (mean age of onset, mid-20s). All had “substantially diminished” health status, but all were able to walk at least 40 m on the 6-minute walk test, with assistive devices permitted, and they had a percentage of predicted forced vital capacity (FVC) of 30%–80% while upright.
Of the 90 study participants, 60 were randomly assigned to receive biweekly infusions of alglucosidase alfa (20 mg/kg of body weight) and 30 to receive placebo infusions.
The dual primary end point was increase in distance walked on the walk test and percentage of predicted FVC after 78 weeks of therapy.
Patients who received active treatment showed a mean increase of 25.1 m on the walk test, while those who received placebo showed a decrease of 3.0 m, for a differential effect of 28.1 m.
Similarly, patients who received active treatment showed a increase of 1.2 percentage points in predicted FVC, while those who received placebo showed a decrease of 2.2 percentage points, for a differential effect of 3.4 percentage points, Dr. van der Ploeg and colleagues said (N. Engl. J. Med. 2010;362:1396–406).
These results were consistent and robust across several methods of data analysis and in all subgroups studied. The findings “indicate that alglucosidase alfa has a positive effect on the complex process that leads to impaired ambulation and respiratory failure in late-onset Pompe's disease,” according to the investigators.
“Patients in the two groups had similar frequencies of adverse events, serious adverse events, treatment-related adverse events, and infusion-associated reactions. Most adverse events were mild or moderate in severity and were not considered to be related to the study drug,” the investigators said.