Mucopolysaccharidosis VI

MPS VI

Mucopolysaccharidosis Type VI (MPS VI) also known as Maroteaux-Lamy syndrome, is part of a group of rare lysosomal storage diseases (LSD) caused by a defect in the catabolism (break down) of glycosaminoglycans (GAGs) and resulting in the progressive accumulation of GAGs in the tissue.1 GAG accumulation is associated with diverse, often debilitating, symptoms that can profoundly impact mobility, activity and quality of life 2,3

Current standard of care includes disease modifying enzyme replacement therapy (ERT), plus supportive medical, surgical or physiotherapy interventions.3Despite available therapies people with MPS VI continue to experience bone and joint manifestations, chronic pain, and physical disability.4

The life expectancy of individuals with MPS VI depends on the severity of symptoms. Without treatment, severely affected individuals may survive only until late childhood or adolescence. Those with milder forms of the disorder usually live into adulthood, although their life expectancy may be reduced.1

Heart disease and airway obstruction are major causes of death in people with MPS VI.5

The incidence of MPS varies between MPS type and region, MPS VI occurs in about 1 in every 240,000 to 300,000 live births.6

Mucopolysaccharidosis VI

MPS VI

Mucopolysaccharidosis Type VI (MPS VI) also known as Maroteaux-Lamy syndrome, is part of a group of rare lysosomal storage diseases (LSD) caused by a defect in the catabolism (break down) of glycosaminoglycans (GAGs) and resulting in the progressive accumulation of GAGs in the tissue.1 GAG accumulation is associated with diverse, often debilitating, symptoms that can profoundly impact mobility, activity and quality of life 2,3

Current standard of care includes disease modifying enzyme replacement therapy (ERT), plus supportive medical, surgical or physiotherapy interventions.3Despite available therapies people with MPS VI continue to experience bone and joint manifestations, chronic pain, and physical disability.4

The life expectancy of individuals with MPS VI depends on the severity of symptoms. Without treatment, severely affected individuals may survive only until late childhood or adolescence. Those with milder forms of the disorder usually live into adulthood, although their life expectancy may be reduced.1

Heart disease and airway obstruction are major causes of death in people with MPS VI.5

The incidence of MPS varies between MPS type and region, MPS VI occurs in about 1 in every 240,000 to 300,000 live births.6

Key MPS VI Figures

Incidence of live births6

≤1/240K

Expected lifespan with severe form1
≤ 20YRS
Expected lifespan with less severe form1
≤ 50YRS
Estimated global market size (USD) by 20277
$706M+

Key MPS VI Figures

Incidence of live births6
≤1/300K
Expected lifespan with severe form1
≤ 20 YRS
Expected lifespan with less severe form1
≤ 50 YRS
Estimated global market size (USD) by 20277

$706M+

Drug in development

Pentosan
Polysulfate
Sodium

for subcutaneous injection

Potential

There is an unmet need to help manage bone and joint manifestations, chronic pain, and physical disability, key clinical manifestations of MPS VI which remain despite treatment with ERT.4
PPS has been shown to reduce GAG levels, inflammatory biomarkers, joint stiffness, and pain in preclinical MPS models and in clinical trials in MPS patients. 8-11
The mechanisms of action of PPS that are relevant to the treatment of MPS include:

- Reduction in systemic and accumulated GAGs in multiple tissues12
- Anti-inflammatory effects via the inhibition of NF-kB resulting in the reduction in pro-inflammatory mediators13
- Reduction in the expression of the pain mediator, nerve growth factor (NGF) in osteocytes from degenerating joints 14
- An ability to inhibit the cartilage degrading enzymes that are related to joint dysfunction observed in MPS15

Remodelling
Inflammation
Pain
Cartilage Loss

Development milestones

Paradigm’s current focus is on MPS Types I and VI, where there is an unmet medical need to manage residual musculoskeletal and pain symptoms.

In 2018, Paradigm entered into an exclusive license agreement for the use of PPS to treat lysosomal storage diseases (LSDs) including MPS (MPS types I, II, III, IV, VI and VII), Gaucher and Fabry diseases. The licensing agreement and accompanying Phase 2a human data is a valuable addition to Paradigm’s product pipelines and IP portfolio. Granted patents cover key regions such as USA, Japan, Europe, Australia and New Zealand.

Paradigm has received Orphan Designations in both the USA and EU for MPS Types I and VI. These designations allow for potentially faster processing times for clinical trials in these regions, more regulatory support from the EMA, and for longer market exclusivity periods in the US and EU.

Considering the encouraging results of PPS effect on pain, function and biomarkers seen in animals and clinical studies reported to date, and the support of global leaders in MPS, Paradigm has commenced a clinical program assessing subcutaneous (SC) injections of PPS in MPS VI.


A 24-week Phase 2 randomised double‐blind placebo‐controlled clinical trial (PARA_MPSVI_001). This study is being conducted at two centres in Brazil. Dr Roberto Giugliani, Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, is the lead investigator, supported by Dr Paula Frassinetti Vasconcelos de Medeiros, Federal University of Campina Grande. The trial will evaluate safety and tolerability of SC PPS in 12 patients with MPS VI who are currently receiving ERT. Secondary endpoints include pain, function, and GAG levels. The study endpoints selected were informed by a patient focus group, the outcomes of which were presented at the Lysosomal diseases conference WORLDSymposium (2019), and published in Orphanet in 2021.16 A poster on the study design and progress of PARA_MPSVI_001 was presented by Dr Giugliani at WORLDSymposium February 7-11, 2022.

Paradigm is interested in exploring strategic partnerships to progress clinical studies to further evaluate PPS as a treatment to address the critical unmet need of ongoing musculoskeletal symptoms in this very rare patient population.

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