Therapy & Treatment

Mucopolysaccharide & related diseases are complex, multi-systemic diseases and their management and care can be extremely complicated.  Due to increased research, new treatments have become available for some types of MPS; however, for some types of MPS & related diseases, treatment remains symptomatic in nature.

 

MPS I:

Aldurazyme (laronidase) enzyme replacement therapy (ERT) was licensed for use by Health Canada on May 31, 2004, for long-term treatment in patients with a confirmed diagnosis of MPS I, to treat the non-neurological manifestations of the disease. For more information, please visit www.aldurazyme.com.

The Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Torrence, California, and the University of Minnesota are collaborated on three studies of intrathecal enzyme replacement therapy (ERT) for patients with MPS I:

MPS I Intrathecal ERT for Spinal Cord Compression (Complete – Results not currenty published):

Enzyme replacement therapy (ERT) has been developed for MPS I. ERT helps many physical ailments due to the disease, but does not treat the central nervous system due to inability to cross the blood brain barrier. The purpose of this study was to test delivery of ERT to the spinal fluid via intrathecal (IT) injection in patients with MPS I to find out whether giving ERT directly into the spinal canal can help reduce spinal cord compression and provide an alternative to surgery.

Study participants had:

  • up to 16 IT ERT treatments given one to three months apart over one-and-a-half years
  • physical examinations (general and neurologic)
  • other diagnostic tests
  • reimbursement of travel expenses

MPS I Intrathecal ERT for Cognitive Decline (Complete – Results not currenty published):

The purpose of this research study was to find out whether giving ERT with Aldurazyme as an injection directly into the cerebral spinal fluid can stabilize or improve cognitive decline in patients who have MPS I. The term “cognitive decline” refers to a change for the worse in the ability to think and learn.

Study participants had:

  • up to 10 treatments given one to three months apart over two years (treatment group) or four treatments given three months apart beginning at month 12 (control group)
  • physical examinations (general and neurologic)
  • neuropsychological testing for cognitive decline and MRI of the brain
  • reimbursement of travel expenses

Additional information can be found at www.clinicaltrials.gov; search under “mucopolysaccharidosis” or contact

Principal Investigator Dr. Patricia Dickson at 310-781-1399 or pdickson@ucla.edu.

MPS I Intrathecal ERT for Children Being Considered for Transplant (Still recruiting):

The University of Minnesota in Minneapolis has obtained FDA approval for the delivery of laronidase into the spinal fluid of children with MPS I (Hurler syndrome)being considered for marrow/cord blood transplantation at the University of Minnesota. The goal of these studies is to decrease the neuropsychologic decline that is generally observed in children with Hurler from the time the patients are initially evaluated to the time they are one year from transplantation.

The study will involve four doses of laronidase given during a lumbar puncture (LP) approximately three months before transplantation, at the time of admission to the hospital for the transplant, three months after the transplant, and six months after the date of the transplant. The LP’s are performed with sedation.

Principal Investigator Dr. Paul Orchard can be contacted for more information at 612-626-2961 or orcha001@umn.edu.

This trial is still recruiting, information can be found on https://bmt.umn.edu/enzyme-replacement-therapy-hurler

Chaperone-Advanced Replacement Therapy (CHART™) program for Mucopolysaccharidosis Type I (MPS I):

Amicus Therapeutics announced in June 2013 a preclinical Chaperone-Advanced Replacement Therapy (CHART™) program for Mucopolysaccharidosis Type I (MPS I). Amicus is developing a proprietary human recombinant IDUA (rhIDUA) enzyme co-formulated with a novel pharmacological chaperone as a next generation therapy for MPS I. Click here for more information.

 

MPS II:

ELAPRASE (idursulfase)Consumer Information
http://www.shirecanada.com/-/media/shire/shireglobal/shirecanada/pdffiles/product%20information/elaprase-ci-en.pdf

On June 15, 2007 Elaprase enzyme replacement therapy (ERT) was  approved by Health Canada for the treatment of MPS II. For more information, please visit www.hunterpatients.com.

Shire MPS II Intrathecal Study:

A Phase I/II (Safety/Dosage) trial using investigational idursulfase—IT for the treatment of MPS II via an intrathecal drug delivery device (IDDD) has been completed and an extension study is ongoing.

HGT-HIT-094 (or “AIM-IT”) is a controlled, randomized, two-arm, open-label, assessor-blinded, multicenter study designed to determine the effect of the Idursulfase-IT regimen in conjunction with IV Elaprase therapy on cognitive and adaptive behaviour. Pediatric patients (3-17 years of age) with MPS II and early cognitive impairment, and who have tolerated Elaprase ERT for a minimum of four months may be eligible for inclusion in this study. All participants will continue to receive weekly ERT infusions while on this study, but of the 42 total patients to be enrolled, there will be a 2:1 ratio of those randomized to receive monthly IT treatment or to a no treatment control arm. Sites are not finalized, but there will be sites in the US and there may be a site in Canada. Click here for more details on these and other Shire-sponsored studies.

Shire is investigating the use of idursulfase that has been formulated for direct administration into the cerebrospinal fluid. It is intended that the drug will be administered directly into the central nervous system via an implanted intrathecal drug delivery device. Long-term administration of intrathecal enzyme replacement therapy (ERT) is an unprecedented approach to delivery of the deficient enzyme directly to the CNS in order to bypass the blood brain barrier. The development plan for the SHP-609 program has been designed for earliest possible registration with the goal of enabling broad access to patients with MPS II who have cognitive impairment. For a comprehensive update on the current status of the development of Shire’s SHP-609 program for MPS II patients with cognitive impairment – including efforts to speed the development of idursulfase-IT – please click here.

 

MPS III:

BMN 250 for MPS IIIB (Sanfilippo Syndrome B)

BMN 250 is an enzyme replacement therapy being developed to treat Sanfilippo B Syndrome.

Mucopolysaccharidosis IIIB (MPS IIIB) or Sanfilippo Syndrome Type B is a lysosomal storage disease belonging to the group of mucopolysaccharidoses. MPS IIIB is caused by deficiency in the enzyme alpha-N-acetyglucosaminidase (NAGLU), one of the four enzymes required for heparan sulfate (HS) degradation in people.

MPS III is unique among the MPS disorders as it is predominantly a neurological disease. In patients with the MPS IIIB subtype, the first symptoms typically appear between the ages of two and six years old, with behavioral disorders, intellectual deterioration, disturbed sleep, and in some cases, very mild dysmorphism. The neurological involvement becomes more prominent with progressive loss of motor milestones and communication problems.  The prognosis is poor with death occurring in most cases of MPS IIIB in the late teens or early 20s.

BMN 250 is an investigational enzyme replacement therapy using recombinant human alpha-N-acetyglucosaminidase (NAGLU) fused with a peptide derived from insulin-like growth factor 2 ( IGF2) or Glycosylation Independent Lysosomal Targeting (GILT) tag. BMN 250 leverages BioMarin’s proprietary technology to deliver large proteins directly to the brain, which bypasses the blood brain barrier. This BioMarin technology, to be used for the treatment of Sanfilippo B patients, builds on the experience the company has gained using this approach to treat CLN2 disease, a form of Batten disease.

There are an estimated 1,000 – 2,000 patients in the developed world with MPS IIIB (Sanfilippo Syndrome Type B).

Current Clinical Trials: MPS IIIB (Sanfilippo B Syndrome)

Study: A Prospective, Observational Study of Mucopolysaccharidosis Type IIIB (MPS IIIB)

Indication: MPS IIIB (Sanfilippo B Syndrome)

Investigational Therapeutic: BMN 250

Study Type: Observational

Goal: The purpose of this multicenter, multinational, longitudinal study is to quantify the progression of MPS IIIB over time and to correlate changes in clinical features of the disease, in particular cognitive decline, with both MRI characteristics and biochemical markers of disease burden. This information may help inform the design and interpretation of subsequent interventional studies.

Status: Recruiting

Additional information: View on Clinicaltrials.gov

Study: A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Intracerebroventricular BMN 250 in Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)

Indication: MPS IIIB (Sanfilippo B Syndrome)

Study Type: Phase 1/2

Goal: The study’s primary objectives are to evaluate the safety and tolerability of BMN 250 administered to subjects with MPS IIIB via an ICV reservoir and catheter and to evaluate the impact of BMN 250 on cognitive function in patients with MPS IIIB as assessed by the Development Quotient.

Status: Recruiting

Additional information: View on Clinicaltrials.gov

 

Phase I/II/IIB Studies of ERT for MPS IIIA:

Shire has completed a safety and dose-ranging study to evaluate the delivery of investigational intrathecal recombinant human heparan N-sulfatase (rhHNS) via an IDDD in 12 patients with MPS IIIA, and an extension study is ongoing at Emma Children’s Hospital, Academic Medical Center in The Netherlands under the direction of Dr. Frits Wijberg, and St. Mary’s Hospital in Manchester, UK under the direction of Dr. Simon Jones. Shire’s natural history studies of individuals with MPS IIIA and MPS IIIB are both closed to enrolment.

HGT-SAN-903 (or “LYRIC”) is a randomized, controlled, open-label, multicenter, Phase IIB safety and efficacy study of HGT-1410 (recombinant  human heparan N-sulfatase, or rhHNS) in pediatric patients with early stage MPS IIIA. The purpose of this study is to assess the potential clinical efficacy of HGT-1410 administered by an intrathecal drug delivery device (IDDD). A total of 18 patients (aged 12 months – 48 months) will be randomized to one of three groups: 45 mg every 2 weeks (6 patients); 45 mg every 4 weeks (6 patients); or a no treatment control arm. Sites are yet to be finalized, but there is a possibility there may be a Canadian site.

Click here for more details on Shire’s programs.

 

Gene Therapy Study to be conducted at Nationwide Childrens Hospital: NEEDS UPDATING
Click here to read more about this study from Nationwide, and here to read the Canadian press release.

Please click here to read about various natural history studies being conducted by Nationwide Children’s Hospital, Shire, Synageva and The Neurodevelopmental Function in Rare Disorders (NFRD) Program at the University of North Carolina at Chapel Hill.

Genistein Aglycone:

Brian Bigger’s research team from the University of Manchester’s MPS Stem Cell Research Laboratory found that “Genistein may prove useful as a substrate reduction agent to delay clinical onset of MPSIIIB and, due to its multimodal action, may provide a treatment adjunct for several other neurodegenerative metabolic diseases.”  Please click here for more information from the UK MPS Society.

A clinical trial of high-dose Genistein Aglycone is taking place in Manchester (UK), with Simon Jones as the principal investigator. Frits Wijburg is also conducting a Genistein study at the Amsterdam Medical Centre.

Click here to view a video (December 2013) featuring Dr. Brian Bigger explaining why this trial is so important.

Click here for a press release (August 2014) concerning this trial: Patient at Royal Manchester Children’s Hospital first to take part in trial of new treatment for rare inherited disease.

Click here to view a patient story about the first child patient to participate in this study.

MPS IIIB AAV gene therapy clinical trial:

Dr. J. M. Heard is leading a MPS IIIB AAV gene therapy clinical trial, conducted at the institute Pasteur in Paris, France.

MPS IIIB natural history study:

In April 2012 Shire enrolled the first participant into a multi-center observational, prospective natural history study of Sanfilippo Syndrome Type B (MPS IIIB) (HGT-SNB-088). The last patient enrolled in the study in September 2013, making a total of 19 patients. The period of observation in this study is 12 months for each patient. A full publication of the results will be made available following the completetion of the study around the end of 2014. Click here to review an update provided in April 2014.

MPS IIIA gene therapy clinical trial:

Lysogene is conducting is an open-label, single arm, monocentric, phase I/II clinical study evaluating the tolerance and the safety of intracerebral administration of adeno-associated viral vector serotype 10 carrying the human SGSH and SUMF1 cDNAs for the treatment of Sanfilippo type A syndrome (P1-SAF-301). The Principal Investigator is Professor Marc Tardieu, Head of Unit, Neuropediatry, CHU Bicêtre, Le Kremlin-Bicêtre (France). Additional information about this clinical trial can be found at http://lysogene.com/en/approach/the-saf-301-program/p1-saf-301-clinical-trial or by visiting http://clinicaltrials.gov/ct2/show/NCT01474343.

 

MPS IV:

Recently CADTH, the Common Drug Review, released a positive decision to reimburse Naglazyme and Vimizim

To date this is a first for CADTH to provide a positive recommendation to reimburse any enzyme replacementtherapy for MPS. A great deal of effort from several members and patient groups, including the Isaac Foundation, were involved in the submission to CADTH and on behalf of the society I would like to sincerely thank everyone who contributed their time to provide input on what the treatments meant to them and/or their family.

Next steps will be for the manufacturer, BioMarin, to discuss terms and conditions for coverage with the pan-Canadian Pharmaceutical Alliance (pCPA). This process may take 6-12 months. BioMarin’s Vimizim Compassionate Use Program for clinical trial patients has been extended until the end of 2016 so the company and provinces (pCPA) can negotiate terms and conditions for coverage.

To review complete decisions and patient submissions please view:

https://www.cadth.ca/galsulfase-SR0434

https://www.cadth.ca/elosulfase-alfa-4  (on the right side of the screen you can click on the final report or patient submission)

Current Clinical Trials: MPS IVA

Study: Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

Indication: MPS IVA (Mucopolysaccharidosis IVA, also known as Morquio A syndrome)

Investigational Therapeutic: BMN 110

Study Type: Phase 3

Goal: This Phase 3 extension study will evaluate the long-term efficacy and safety of BMN 110 2.0 mg/kg/week and/or BMN 110 2.0 mg/kg/every other week in patients with mucopolysaccharidosis IVA (Morquio A Syndrome).

Status: This study is ongoing, but not recruiting participants

Additional information: View on Clinicaltrials.gov

Study: Study of BMN 110 in Pediatric Patients < 5 Years of Age With Mucopolysaccharidosis IVA (Morquio A Syndrome)

Indication: MPS IVA (Mucopolysaccharidosis IVA, also known as Morquio A syndrome)

Investigational Therapeutic: BMN 110

Study Type: Phase 2

Goal: This open-label Phase 2 study will evaluate the safety and efficacy of weekly 2.0 mg/kg/wk infusions of BMN 110 in pediatric patients, less than 5 years of age at the time of administration of the first dose of study drug, diagnosed with MPS IVA (Morquio A Syndrome) for up to 208 weeks.

Status: This study is ongoing, but not recruiting participants

Additional information: View on Clinicaltrials.gov

Completed Clinical Trials: MPS IVA

Study: Efficacy and Safety Study of BMN 110 for Morquio A Syndrome Patients Who Have Limited Ambulation

Indication: MPS IVA (Mucopolysaccharidosis IVA, also known as Morquio A syndrome)

Investigational Therapeutic: BMN 110

Study Type: Phase 2

Goal: The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a patient population that has limited ambulation, in a period of up to 144 weeks.

Status: This study has been terminated

Additional information: View on Clinicaltrials.gov

Study: A Clinical Assessment Study of Subjects With Mucopolysaccharidosis IVA (Morquio Syndrome)

Indication: MPS IVA (Mucopolysaccharidosis IVA, also known as Morquio A syndrome)

Investigational Therapeutic: BMN 110

Study Type: Observational

Goal: This multicenter, multinational, longitudinal study will quantify endurance and respiratory function in subjects diagnosed with MPS IVA and will better characterize the spectrum of symptoms and biochemical abnormalities in MPS IVA disease over time.

Status: This study has been terminated

Additional information: View on Clinicaltrials.gov

Study: A Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

Indication: MPS IVA (Mucopolysaccharidosis IVA, also known as Morquio A syndrome)

Investigational Therapeutic: BMN 110

Study Type: Phase 2

Goal: This multicenter, open-label extension study is designed to assess long-term efficacy and safety of 2.0 milligrams (mg)/kilogram(kg)/week of BMN 110 in patients diagnosed with Mucopolysaccharidosis IVA (MPS IVA)

Status: This study has been terminated

Additional information: View on Clinicaltrials.gov

Study: Safety and Exercise Study of BMN 110 for Morquio A Syndrome

Indication: MPS IVA (Mucopolysaccharidosis IVA, also known as Morquio A syndrome)

Investigational Therapeutic: BMN 110

Study Type: Phase 2

Goal: The primary objective of this study is to evaluate the safety of a 2.0 mg/kg/week and a 4.0 mg/kg/week of BMN 110 in patients with Morquio A syndrome for up to 192 weeks. Secondary objectives will investigate the effect of the two doses on exercise capacity for up to 192 weeks. In addition, the pharmacokinetic (PK) parameters of both doses of BMN 110 will be assessed

Status: This study has been terminated

Additional information: View on Clinicaltrials.gov

 

BioMarin Pharmaceutical Inc. has concluded its Phase III study (MOR-004) for N-acetylgalactosamine 6-sulfatase (GALNS) for the treatment of Morquio A Syndrome (MPS IVA) and has applied for approval from the US FDA and Health Canada. Please click here to read BioMarin’s December 4, 2013 Press Release.

There were three Canadian sites involved with this trial: Montreal and Sherbrooke, Quebec and Toronto, Ontario, and an additional site in Calgary for an additional study investigating cardio-pulmonary effects of GALNS (MOR-008).

BioMarin’s MPS IV A program’s website (www.morquiobmrn.com) is a great place to look for current information. In addition to the MOR-004 and MOR-008 studies, BioMarin is also conducting an “under 5” study (MOR-005) and a “non-ambulatory” study (MOR-006).

Further information about BioMarin’s MPS IV A program is available at www.clinicaltrials.gov at this link: http://www.clinicaltrials.gov/ct2/show/NCT00787995?term=morquio&rank=2.

For additional medical questions related to MPS IV A and the clinical details of BioMarin’s program, please contact the Medical Director for BioMarin’s MPS IV A program, Celeste Decker, at cdecker@bmrn.com or 415-506-6469.

MPS IV B Registry:

The Canadian MPS Society, through its MPS IV B Fund, is funding a Registry for MPS IV B/late-onset GM-1 Gangliosidosis. For more information, please visit www.morquiob.org.

 

MPS VI: 

The U.S. Food and Drug Administration (FDA) granted marketing approval for Naglazyme(TM) (galsulfase), enzyme replacement therapy (ERT) for the treatment of  MPS VI, on June 1, 2005. BioMarin received licensing approval for Naglazyme in Canada this September (2013). For more information please contact BioMarin Pharmaceutical Inc., Commercial Operations at: 1-415-506-6700.

 

MPS VII: 

In August 2013, Ultragenyx Pharmaceutical Inc. received Approval of its Clinical Trial Application for a Phase I/II Trial Testing UX003 in Mucopolysaccharidosis Type VII (MPS VII). Click here to read the company’s press release regarding this study. For more information, visit www.ultragenyx.com.

Phase 3 study design: https://www.clinicaltrials.gov/ct2/show/NCT02230566?term=mps+7&rank=1

Press releases are posted online at:

http://ir.ultragenyx.com/releases.cfm?Year=&ReleasesType=&PageNum=1&SortOrder=Date%20Descending&NumberPerPage=10

 

Pompe Disease:

Enzyme Replacement Therapy

MYOZYME® (alglucosidase alfa), a recombinant form of human acid alpha-glucosidase (GAA), was approved by Health Canada on August 14, 2006 for the treatment of patients with Pompe disease (GAA deficiency). The approval of MYOZYME represents a significant  milestone in the management of Canadian patients with Pompe disease as it is the first etiology specific therapy for this rare, rapidly progressing, and often fatal disease.

All patients with Pompe disease have an inherited deficiency of the enzyme GAA, which works optimally in the lysosome to convert glycogen to glucose. GAA deficiency lead to glycogen accumulation in, and eventually rupture of, the lysosome resulting in cellular dysfunction, particularly in cardiac, respiratory, and skeletal muscle tissue.

Prior to the approval of MYOZYME there was no approved treatment for Pompe disease that focused on the cause of the disease. Palliative and supportive care was the mainstay of treatment. The approval of MYOZYME will provide a therapeutic option for patients to manage this devastating disease.

CANADIAN ASSOCIATION OF POMPE (CAP)

The goal of CAP is to provide support for Canadians with Pompe disease and to raise awareness of Pompe disease in Canada and elsewhere. For more information, please visit http://www.pompecanada.com/.

Alpha-Mannosidosis:

Study of outcomes from transplants for Alpha-Mannosidosis
Dr. Martin Myranek from Hanover Medical School is conducting a study on the outcomes of transplants for Alpha-Mannosidosis.  View the results at www.mannosidosis.org.

Clinical Trial of Enzyme Replacement Therapy for Alpha-Mannosidosis
The Scandinavian company Zymenex has been working for over 10 years to develop a number of Enzyme Replacement Therapies for Lysosomal diseases, including Mannosidosis. Please visit www.ISMRD.org for more information.

 

Please visit our Resources page for a full listing of our educational booklets, and for links to many informative websites.