Introducing NEXVIAZYME:

An ERT for LOPD1

MECHANISM OF ACTION

NEXVIAZYME is an ERT for LOPD designed with ~15 mol M6P per mol enzyme. Alglucosidase alfa’s surface contains ~1 mol M6P per mol enzyme.1,2

Statistical superiority of NEXVIAZYME over alglucosidase alfa was not achieved in a clinical study.

WHAT IS M6P?


Mannose 6 phosphate, or M6P, is a residue that binds with M6P receptors (CI‑MPR), mediating the uptake of ERT into muscle cells.3-5

See how NEXVIAZYME works

NEXVIAZYME PHARMACODYNAMICS: ROLE IN GLYCOGEN DEGRADATION

NEXVIAZYME demonstrated a reduction in urinary glucose tetrasaccharide (Glc4) levels during a phase 3 clinical trial1

NEXVIAZYME™ (avalglucosidase alfa-ngpt) pharmacodynamic data alglucosidase alfa (SD=32) NEXVIAZYME (SD=24) 0 -20 -60 -40

Mean percentage change in urinary Glc4 concentrations from baseline to week 49

The baseline mean urinary Glc4 concentration was 12.7 mmol/mol and 8.7 mmol/mol in NEXVIAZYME and alglucosidase alfa treatment groups, respectively.1

54%

reduction in urinary
Glc4 concentration
over 49 weeks in a
phase 3 clinical trial1

Urinary Glc4 concentrations
were normalized by urine
creatinine and reported as
mmol Glc4/mol creatinine.1
The clinical relevance of urinary
Glc4 concentrations has not
been determined.

SD=standard deviation.

WHAT IS GLC4?


In patients with late-onset Pompe disease, excess of glycogen is degraded to hexose tetrasaccharide (Hex4) which is then excreted in urine. The urinary Hex4 assay measures its major component, Glc4.1

CLINICAL TRIAL RESULTS

COMET TRIAL:

A head to head study comparing NEXVIAZYME and alglucosidase alfa1

NEXVIAZYME™ (avalglucosidase alfa-ngpt) trial enrollment and study design
NEXVIAZYME TRIAL STUDY DESIGN TABLE
*Screening phase (up to 14 days), may be extended to up to 8 weeks in prespecified situations.
Randomization at a 1:1 ratio with stratification factors based on baseline FVC, sex, age, and country (Japan or ex-Japan).
NEXVIAZYME infusion, safety assessments, and efficacy evaluations.
6MWT=6-Minute Walk Test; FVC=forced vital capacity; qow=every other week.

Comet trial:

NEXVIAZYME IMPROVED OR STABILIZED BOTH RESPIRATORY FUNCTION AND WALKING CAPACITY COMPARED WITH BASELINE1

When compared head to head with alglucosidase alfa, NEXVIAZYME® (avlaglucosidase alfa-ngpt) demonstrated a favorable numerical treatment difference.1*

PRIMARY ENDPOINT

NEXVIAZYME™ (avalglucosidase alfa-ngpt) FVC efficacy data

At 49 weeks, NEXVIAZYME improved FVC (% predicted)1:

+2.9pp

compared with
baseline

+2.4pp

compared with
alglucosidase alfa

* Noninferiority margin of 1.1% (p=0.0074). Statistical superiority of NEXVIAZYME over alglucosidase alfa was not achieved (p=0.06).
LS=least squares; pp=percentage points.

SECONDARY ENDPOINT

NEXVIAZYME™ (avalglucosidase alfa-ngpt) 6MWT efficacy data

At 49 weeks, NEXVIAZYME improved 6MWT1:

+32.2meters

compared with baseline

+30.0meters

compared with
alglucosidase alfa

p value at nominal level, without multiplicity adjustment.

SAFETY

NEXVIAZYME demonstrated its safety profile over 49 weeks in the COMET study.1

Adverse reactions reported in ≥6% of patients treated with NEXVIAZYME1

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Adverse Reaction Table

Infusion-associated reactions

IARs were reported in 25% (13/51) of patients treated with NEXVIAZYME and 33% (16/49) of patients treated with alglucosidase alfa. Mild-to-moderate IARs reported in more than 1 patient with NEXVIAZYME were headache, diarrhea, pruritus, urticaria, and rash.1 No patients receiving NEXVIAZYME experienced severe IARs.1

Serious ARs and treatment discontinuations

Serious ARs were reported in 2% (1/51) of patients treated with NEXVIAZYME and 6% (3/49) of those treated with alglucosidase alfa.1

AR=adverse reaction; IAR=infusion-associated reaction.