Results of a Phase 4 clinical trial support the effectiveness of Lumizyme (4,000 liters recombinant human GAA) for 52 weeks in maintaining clinical stability in Pompe disease patients previously treated with the therapy’s 160-liter formulation, called Myozyme.
The study, “Efficacy, safety profile, and immunogenicity of alglucosidase alfa produced at the 4,000-liter scale in US children and adolescents with Pompe disease: ADVANCE, a phase IV, open-label, prospective study,” was published in the journal Genetics in Medicine.
Pompe disease is caused by a deficiency in an enzyme, called acid α-glucosidase (GAA), leading to glycogen accumulation and muscle damage.
Later in 2010, a larger 4,000-liter scale of recombinant human GAA, sold under the brand name Lumizyme (alglucosidase alfa), also received FDA approval.
Sanofi Genzyme sponsored the Phase 4 ADVANCE trial (NCT01526785) to further evaluate the safety and effectiveness of treatment with Lumizyme in Pompe disease patients.
The trial, which was stopped after the FDA approved the label expansion, enrolled 113 patients, 87 with infantile-onset Pompe disease (IOPD) and 26 with late-onset Pompe disease (LOPD).
Patients were allowed to enroll in the study if they had been previously treated with Myozyme, the 160-liter recombinant human GAA dose.
In the trial they received Lumizyme (4,000 L alglucosidase alfa) for 52 weeks, dosed the same way as the previous routine treatment with Myozyme.
The study’s primary objective, or endpoint, assessed the therapy’s efficacy by measuring the percentage of participants’ who were clinically stable or showed improvements at week 52.
The efficacy of Lumizyme also meant there were no deaths, patients didn’t require assisted ventilation, and they showed no signs of worsening cardiac, respiratory, or motor muscle function.
Secondary endpoints included overall and invasive ventilator-free survival, changes from baseline (start of study) in cardiac, motor, and respiratory muscle functioning, and safety profile.
Of the 113 who started, 104 patients completed the 52 weeks of treatment.
Results showed that 83.7% of the patients (87 out of 104) who transitioned from Myozyme to Lumizyme remained clinically stable or improved after the 52-week trial.
Decline of gross motor function, determined using the GMFM-88 test, was the most common reason for the remaining 16.3% of patients who failed to reach the trial’s primary goal.
Also, overall survival was 98.1% (97.6% for IOPD and 100% for LOPD) and overall invasive ventilator-free survival was 92.4% (93.4% IOPD, 88.7% for LOPD) at week 52.
During the trial, 35 patients had infusion-associated reactions, including infections and gastrointestinal disorders, among others. Eight IOPD patients died of causes unrelated to the therapy.
“ADVANCE efficacy results showed that treatment with 4,000 L rhGAA for 52 weeks maintained clinical stability in most patients with Pompe disease who transitioned from 160 L rhGAA,” the study concluded.
Patients with Pompe disease, a rare muscle disorder, are born with a gene mutation that doesn’t produce enough of the enzyme acid alpha-glucosidase (GAA), which is needed to break down glycogen (sugar stores).
An accumulation of glycogen in muscle cells can lead to heart and respiratory problems, heart failure, and possibly death.