Paradigm Biopharmaceuticals

A bright, well-equipped research laboratory photographed past racks of glass flasks and pipettes, with a researcher in a white coat working at the bench with her back to the camera.

Enrolment in PARA_MPSVI_001 began in August 2021 and completion was declared at Paradigm’s Annual General Meeting in November 2024.

MPS VI study complete

The open-label MPS I study PARA_MPSI_001 was published in the Journal of Inherited Metabolic Disease in 2024.

MPS I study published

Paradigm has completed Phase 2 clinical studies in both MPS I and MPS VI. Further development of these programmes may be progressed in collaboration with a strategic partner or considered following completion of key milestones within Paradigm’s osteoarthritis development programme. No additional clinical studies are currently planned.

A partner for MPS 

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A glass pipette releasing a single drop above a row of laboratory test tubes, two of them holding pale green and pink liquid, against a blue background.

Stylised three-dimensional molecular render in violet and magenta, representing the PPS molecule.

Anatomical three-dimensional render of a knee joint, with the cartilage surfaces inside the joint highlighted in red.

The open-label, single-centre study of subcutaneous pentosan polysulfate sodium in MPS I (PARA_MPSI_001) was published in the Journal of Inherited Metabolic Disease in 2024. DOI 10.1002/jimd.12715.

Journal of Inherited Metabolic Disease, 2024

The MPS I study, published

The endpoints of PARA_MPSVI_001 were informed by a patient focus group, first presented at the WORLDSymposium lysosomal diseases conference in 2019 and published as Leiro et al., Orphanet Journal of Rare Diseases (2021) 16:500. DOI 10.1186/s13023-021-02113-8.

Orphanet Journal of Rare Diseases, 2021

How the MPS VI endpoints were chosen

The MPS VI trial is registered with ReBEC under RBR-2tz9dky. The registry record carries the trial's design, sites and status independently of this page.

Brazilian Registry of Clinical Trials (ReBEC)

PARA_MPSVI_001 registry record

Paradigm maintains a single list of its peer-reviewed publications across all indications, including osteoarthritis, mucopolysaccharidoses and alphavirus-induced arthralgia.

Across Paradigm's programmes

Every peer-reviewed publication

Lysosomal Storage Diseases

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Paradigm's focus in lysosomal storage diseases is on mucopolysaccharidosis types I and VI, where an unmet medical need remains to manage residual musculoskeletal and pain symptoms. Two clinical studies of subcutaneous injectable pentosan polysulfate sodium have been conducted in that setting: a randomised, double-blind, placebo-controlled study in MPS VI, and an open-label study in MPS I. Neither is recruiting.

Both studies took safety and tolerability as their primary objective. Pain, function and glycosaminoglycan (GAG) levels sat among their secondary and exploratory measures. Paradigm holds orphan designations for MPS I and MPS VI in both the United States and the European Union.

Lysosomal storage diseases are a group of rare inherited disorders that affect the body’s ability to break down and recycle certain substances within cells. Over time, this build-up can cause progressive damage to organs, tissues and the nervous system. Because many of these conditions are lifelong, complex and currently have limited treatment options, they represent an important area for continued research and therapeutic development.

Mucopolysaccharidosis Type I (MPS I), also known as Hurler (severe MPS I), Scheie, and Hurler-Scheie (attenuated / less severe MPS I) syndrome is part of a group of rare lysosomal storage diseases (LSD) caused by reduced levels, or the complete lack of, an enzyme responsible for the catabolism (break down) of glycosaminoglycans (GAGs) and resulting in the progressive accumulation of GAGs in the tissue. 1

GAG accumulation has a direct effect on connective tissue formation and function, causing progressive cellular damage affecting multiple organ systems and can lead to organ failure, cognitive impairment and reduced life expectancy. 1

People with severe MPS I typically have an earlier onset of symptoms, a decline in intellectual function, and without treatment individuals with severe MPS I typically die before 10 years of age. 1

Attenuated MPS I typically has a later onset of symptoms, milder symptoms and slower disease progression. While individuals with attenuated MPS I may develop significant disease-related morbidity, they typically show normal intelligence and may survive into adulthood. 1

Heart disease and airway obstruction are major causes of death in all people with MPS I. 2

Current standard of care for MPS includes haematopoietic stem cell transplantation (HSCT) and/or disease modifying enzyme replacement therapy (ERT), or supportive medical and surgical interventions. 3

Despite available therapies people with MPS diseases continue to experience bone and joint manifestations, chronic pain, and physical disability, which generally persist despite treatment with HSCT and ERT. 3

MPS I is present in about 1 in every 100,000 live births. 4

In 2018, Paradigm entered into an exclusive license agreement for the use of PPS to treat lysosomal storage diseases including MPS (MPS types I, II, III, IV, VI, and VII), Gaucher and Fabry diseases. The licensing agreement 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.

In addition, Paradigm has an exclusive supply and license agreement with the only FDA-approved PPS supplier, bene pharmaChem, extending for 25 years post registration.

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.

Paradigm received Orphan Designations in both the USA and EU for MPS Types I and VI. These designations allow for faster processing times for clinical trials, 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 to date, Paradigm has commenced an open‐label single‐centre pilot study assessing SC injections of PPS in participants with MPS I who have received ERT and/or HSCT (PARA_MPSI_001).

The primary objective of the study is to evaluate safety and tolerability of PPS over a 48‐week period. Secondary and exploratory objectives include pain, function, and quality of life, pharmacokinetics, biomarkers, and inflammatory processes.

The study is being conducted at the Adelaide Women’s and Children’s Hospital. Four patients are enrolled and three have completed the study.

Preliminary data from the first three patients was presented at the International Congress of Inborn Errors of Metabolism (ICIEM) 2021. The data showed PPS was well tolerated out to 24 weeks and there was an overall trend toward improvement in pain, function, activities of daily living and quality of life.

View MPS I Poster 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.

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. 3 Despite 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

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.

View MPS VI Poster 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.

The cost and complexity of starting with a new molecule is high, encourages iterative progress and reduces the potential for genuine discovery.

Looking for alternative and equally innovative avenues to address unmet needs, Paradigm identified the potential of PPS, an FDA-approved drug that has a long track record of treating inflammation.

PPS was developed in the 1940s, and has been widely used to treat bladder inflammation (interstitial cystitis) and in the EU for preventing deep vein thrombosis.

By working closely with the proprietary manufacturer of PPS, we are able to build upon the substantial knowledge and expertise available from earlier regulatory filings. This includes decades of accumulated toxicology safety data, manufacturing ‘know-how’, and extensive published information about PPS’s mechanisms of action – which primarily involve interactions with proteins impacting inflammation.

With the existing foundation in PPS, Paradigm aims to minimise the risks associated with early-stage drug development.

In 2018 Paradigm entered into an exclusive licence agreement for the use of PPS to treat lysosomal storage diseases, including MPS types I, II, III, IV, VI and VII, Gaucher and Fabry diseases. Granted patents cover key regions including the USA, Japan, Europe, Australia and New Zealand.

Paradigm’s immediate commercial focus is the development of injectable PPS (iPPS, brand name Zilosul®) for the treatment of osteoarthritis (OA). This is a global unmet need and Paradigm has advanced to phase 3 trials in the space.

Other indications under investigation for PPS include the treatment of joint function, mobility, and pain in patients with mucopolysaccharidoses (MPS); treating alphavirus-induced arthralgia (such as Ross River virus and Chikungunya); chronic heart failure (HF); acute respiratory distress syndrome (ARDS); and allergic respiratory conditions, including allergic rhinitis (AR).

Paradigm continues to progress the development of Zilosul® with the IND (Investigational New Drug) cleared by the US FDA in October 2021.

The published record for Paradigm's two mucopolysaccharidosis studies, and the public registry entry for the MPS VI trial. Each link resolves to the publisher or registry, not to a copy hosted here.

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