A Phase 3 Randomized, Multicenter, Multinational, Double-blinded Study Comparing the Efficacy and Safety of Repeated Biweekly Infusions of NeoGAA (GZ402666) and Alglucosidase Alfa in Treatment naïve Patients with Late-onset Pompe Disease

Pompe disease is a rare, inherited disease caused by the deficiency of the
enzyme acid alfa-glucosidase. This enzyme normally breaks down sugar stored as
glycogen into glucose that can be used for energy by the body's cells. If the
enzyme is not present, glycogen builds up in certain tissues, particularly
muscles, including the heart and the diaphragm (the main breathing muscle under
the lungs). The progressive build up of glycogen causes a wide reange of
symptoms, including an enlarged heart, breathing difficulties and muscle
weakness. The disease can appear at birth (the 'infantile-onset' form) but also
later in life (the 'late onset' form).

The overall objective of this study is to evaluate the efficacy and safety of
neoGAA in treatment-naïve patients with LOPD as compared to alglucosidase alfa,
when this is administered biweekly for a period of 49 weeks. Also, there is an
open-label follow up included, to measure the long term effects of neoGAA
administration.

A phase 3 randomized, multicenter, multinational study with a double-blinded
treatment phase, followed by an open-label follow up phase.

biweekly intravenous injections with neoGAA or alfa glucosidase, in a dose of
20 mg/kg.
After 49 weeks all patients will receive neoGAA 20 mg/kg for the remaining
period of the study.

24 patients were treated in the TDR12857 study, and results showed
effectiveness and an expected safety profile of neoGAA in Pompe patients.

Risks
• Functional testing: falls, shortness of breath, muscle soreness, and fatigue
• Repeat blood draws: momentary discomfort, bruising, excessive bleeding,
infection, fainting, and possible anemia. According to the WHO criteria, the
blood draws are classified as minimal risk (Howie, SRC. Bull World Health
Organ 2011; 89:46-53).
-questionnaires: these are quality of life related and Pompe disease. Children
will receive special questionnaires.
• Administration of medications:
So far 24 patients were treated with neoGAA, and the extension study (LTS13769)
is still running in which all patients receive 20 mg/kg neoGAA.
8 out of 24 patients received and infusion reaction. Most of these reactions
were mild to moderate and resolved spontaneously, except for one patient whom
experienced a severe allergic reaction with respiratory problems and chest
pressure.
The most common side effect was headache (10 patients out of 24), then fatigue
and muscle pain (6 patients out of 24 each) and redness (3 out of 24 patients).

About one third of the adults with Pompe disease experience infusion reactions
during or after the infusion with Myozyme. The majority of the reactions are
characterized as mild to moderately sever and resolved spontaneously.

The most common infusion reactions from NeoGAA are:

- difficulty breathing, abnormal breathing sounds
- swelling of the lips and tongue,
- throat pressure.
- chest pressure,
- abnormal heart beating
- caughing,
- redness, itch and redness of the face
- generalized rash
- dizziness, drop in bloodpressure
- nausea,
- acid reflux
- skin reaction at infusion site,
- headache,
- muscle ache