Morquio Syndrome, also known as Mucopolysaccharidosis Type IV (MPS IV), is a rare genetic disorder caused by the deficiency of the enzymatic activity of N-acetylgalactosamine-6-sulfatase (GALNS). This enzymatic deficiency results in the abnormal accumulation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S), in tissues and organs throughout the body. Morquio A syndrome is caused by mutations in the GALNS gene while the underlying cause of Morquio B syndrome remains unknown. If left untreated, Morquio syndrome can result in severe skeletal dysplasia, spinal cord compression, heart disease, respiratory complications and early death. Currently, there is no cure for Morquio syndrome and management focuses on supportive therapies to address symptoms.
Development of Morquio Syndrome (MPS-IV) Drug Industry
In recent years, significant progress has been made in developing an enzyme replacement therapy (ERT) for Morquio syndrome. ERT aims to restore GALNS enzyme activity levels in patients by intravenous administration of recombinant human GALNS (rhGALNS). The idea behind ERT is that the administered rhGALNS enzyme will be taken up by cells and break down accumulated KS and C6S GAGs.
In 2014, the biotechnology company BioMarin received FDA approval for the first ERT for Morquio Syndrome (MPS-IV) Drug. Vimizim was shown to be well tolerated in clinical trials and resulted in improvements in 6-minute walk test distances and pulmonary function. In 2016, Vimizim also received EU approval and has since been approved in over 40 other countries worldwide. While Vimizim has been a breakthrough for Morquio A patients, its high cost remains a barrier for access in many countries.
Another promising ERT currently in development is BMN 307, being investigated by BioMarin. BMN 307 utilizes a novel fusion technology that links rhGALNS to an antibody fragment to potentially enhance cellular uptake of the enzyme. In Phase 1/2 studies, BMN 307 appeared safe and was associated with reductions in urinary KS. BioMarin is now conducting a global Phase 3 study of BMN 307 expected to be complete in 2022. If approved, BMN 307 could be a more effective treatment option than Vimizim for MPS IV A patients around the world.
Improving Affordability and Global Access
While significant advances have been made in developing ERTs for Morquio syndrome, affordability and access remain major barriers globally – especially in lower and middle-income countries. The high drug acquisition costs of treatments like Vimizim, often over $500,000 annually per patient, are challenging for public healthcare systems to cover. Developing alternative pricing models and ensuring approved treatments are affordable in global markets will be crucial to deliver on the promise of new therapies.
BioMarin has implemented various access programs aimed at expanding the availability of Vimizim treatment. This includes the Ambassador Program which provides Vimizim at no cost for eligible patients unable to access therapy through their national healthcare system or private insurance. However, sustainable approaches are still needed for the long-term given the lifelong treatment required. Partnerships between industry, clinical experts and patient advocacy groups will be important to establish workable frameworks accommodating local economic factors.
Generic competition once patents expire may also play a role in driving down prices over time – though this will likely be many years away still. In the meantime, collaborations focused on local manufacturing and technology transfers could help stimulate development of more affordable biosimilars in emerging markets. Ideally, regulatory harmonization across regions will streamline pathways for these follow-on products. With a global prevalence of 1 in 300,000 live births, no patient should be deprived treatment due to financial constraints alone.
Implications for the Future of MPS IV Management
If ongoing trials are successful, BMN 307 has the potential to become a new standard of care for Morquio A syndrome patients worldwide. Its enhanced intracellular delivery mechanism may translate to better clinical outcomes compared to Vimizim. Combined with potential additional approval of therapies addressing specific organ involvement like cardiopulmonary complications, management of Morquio syndrome is evolving into a multidisciplinary treatment paradigm.
Ensuring therapies are accessible globally will be mission critical. Continued advocacy efforts and cooperation between industry, governments, and patient groups will be required to establish sustainable frameworks expanding access. Overcoming financial barriers should unlock the full benefits of these novel treatments for all MPS IV populations. With committed collaboration, the future remains hopeful for significantly improving quality of life and life expectancy for those living with Morquio syndrome globally.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it