AAN 2016: New ERT for Pompe Disease Shows Promise

James Radke, PhD

Pompe disease is a rare genetic neuromuscular disorder caused by an excessive buildup and storage of glycogen in muscle cells, resulting in degenerative muscle weakness that can affect many body parts and cause numerous health problems. Symptoms include difficulty walking, trouble breathing, headache, enlarged heart, and failure to thrive. In infants, symptoms can begin early and be life-threatening, while those who present with the condition later in life (late-onset Pompe disease) may go several years before being properly diagnosed. The rare condition is due to the absence or deficiency of the lysosomal enzyme alpha-glucosidase (GAA).
Currently, 1 enzyme replace therapy (ERT) is available—alglucosidase alfa—and other ERTs are in development.
At the 68th Annual Meeting of the American Academy of Neurology, held April 15-21 in Vancouver, BC, Pena and colleagues reported on a phase 1 study investigating an ERT—neoGAA—in patients with late-onset Pompe disease.


This open-label, ascending-dose study evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of neoGAA, a second-generation ERT, in 10 treatment-naïve and 14 alglucosidase alfa-experienced (≥9 months of treatment) patients with late-onset Pompe disease.

Adult patients who could walk ≥50 meters independently and had upright forced vital capacity (FVC) ≥50% predicted at baseline received intravenous neoGAA (5, 10, or 20 mg/kg every other week for 24 weeks.


A total of 9 treatment-naïve patients (5 mg/kg, n = 3; 10 mg/kg, n = 3; 20 mg/kg, n = 3) and 12 treatment-experienced patients (5 mg/kg, n = 3; 10 mg/kg, n = 4; 20 mg/kg, n = 5) completed the 24-week study.
NeoGAA was well tolerated in both groups. Quadriceps muscle biopsy glycogen levels were low (~6%) in most patients in both groups at baseline, and remained mostly unchanged.
In treatment-naïve patients, percent sitting-FVC remained stable or increased from baseline to Week 25 (mean±SD changes: 5 mg/kg, −2.7±8.8%, n = 4; 10 mg/kg, +4.3±4.9%, n = 3; 20 mg/kg, +6.2±3.2%, n = 3), while maximal expiratory pressure (MEP) and maximal inspiratory pressure (MIP) percent predicted improved or remained stable (respective mean ± SD changes: 5 mg/kg, +8.1±2.8%, n = 2, +6.1±0.79%, n = 2; 10 mg/kg, 16.5±8.0%, n = 3, 10.6±4.9%, n = 3; 20 mg/kg, 12.0±4.1%, n = 3; 7.9 ±15.7%, n = 3).
In treatment-experienced patients, percent predicted sitting-FVC remained stable from baseline to Week 25 (5 mg/kg, −0.5±4.3%, n = 4; 10 mg/kg, −2.0±2.2%, n = 4; 20 mg/kg, +1.4±5.7%, n = 5), as did percent predicted MEP and MIP (respective mean ± SD changes: 5 mg/kg, −3.5±10.8%, n = 4, +10.5±7.3%, n = 4; 10 mg/kg, +15.7±38.4%, n = 3, +4.2±12.6%, n = 3; 20 mg/kg, +6.0±21.8%, n = 5; −0.2±6.9%, n = 5).
Six-minute walk test distances were generally stable or increased with neoGAA without relationship to patient group or dose level. The Quick Motor Function Test and hand-held dynamometry scores improved in both groups, regardless of dose, while Gait, Stairs, Gower, Chair and Gross Motor Function Measure scores showed minimal changes across groups and all dose levels.

Although this was a phase 1 study and the efficacy results were exploratory, the researchers concluded that the results support further development of neoGAA to treat patients with late-onset Pompe disease.

In the clip below, we talked with lead author Loren Del Mar Pena, MD, PhD, of Duke University Medical Center about the study.


Pena L, Barohn R, Byrne B, et al; NeoGAA Investigator Group. Phase 1 exploratory efficacy of the novel enzyme replacement therapy neoGAA in treatment-naïve and alglucosidase alfa-treated late-onset Pompe disease patients. Poster presented at: 68th Annual Meeting of the American Academy of Neurology; April 15-21, 2016; Vancouver, BC. Abstract I4.011.
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