MLD Enzyme Replacement Therapy (ERT)

SUMMARY & ADDITIONAL DETAILS

Study Summary – Weekly intrathecal injections for 105 weeks via an intrathecal drug delivery device (IDDD) or port implanted in the patient’s abdomen.

What is a Clinical trial? – Clinical trials are research studies performed in people that are aimed at evaluating a medical, surgical, or behavioral intervention. They are the primary way that researchers find out if a new treatment, like a new drug or medical device (for example, a pacemaker) is safe and effective in people. Efficacy, while desired and measured, cannot be guaranteed.

Infusion Time – The weekly infusion is expected to take just a few minutes, but it is likely patients will be monitored for an hour or two after each infusion to watch for any allergic reactions – which are not likely but is part of understanding the drug.

Cohorts – The study will be performed with 35 patients divided into four cohorts at varying degrees of disease progression.

Matched Historical Controls – these are untreated patients that will be identified through a separate CHOP natural history study and matched to treated patients based on medical history and progression. This enables Takeda to compare the efficacy of therapy to the natural history of untreated disease.

Enzyme – Recombinant human arylsulfatase A, which is expected to work in the same way as normal human arylsulfatase using a method known as “recombinant DNA technology”: it is made by human cells that have received a gene (DNA) that makes them able to produce arylsulfatase A.

Intrathecal Port – The spinal fluid naturally circulates between the spinal column and the brain 3.7 times per day and it is on the “other side” of the blood-brain barrier that is a typical barrier to an intravenously delivered enzyme.* This intrathecal therapy delivers the enzyme directly into the spinal fluid. In order to minimize the chances of infection or injury due to repeated spinal puncture, a small port (a little larger than a US dime in diameter) will be implanted in the abdomen just under the skin – usually on the patient’s side or front which is connected via a very small catheter to spine and into the CSF.* The Enzyme is injected through the skin into the port and transfers via the catheter (tubing ) to the spinal fluid. This port is being studied as an integral part of the Clinical Trial. Please note – this is a static bolus device, not a pump. The image is the new (December 2013) Sophysa mini Soph-A-Port®.

Placing the port and catheter is a minor surgery and will require sedation. Please ask us about how to best sedate MLD patients for this surgery.

24 International & US Sites – United States (California, Florida, Illinois, Iowa, Minnesota, New York, Ohio, Pennsylvania, Utah) Belgium, Brazil, Canada, Denmark, France, Germany, Israel, Japan, Mexico, Netherlands, Spain, United Kingdom.

You may enroll and start therapy at one site and then transfer to another site closer to home as it opens.

==> Details for each site, including contact information, can be found here.

Local Infusion Sites – Enrollment and periodic assessments must be at a primary study site (see above), however, it is Takeda’s desire to enable the weekly infusions to occur locally, if appropriate local resources are available. These local resources will have to be evaluated, authorized, and trained on a case by case basis.

Continuation of Enzyme Access After the Primary Study Period – Takeda has indicated they will continue to supply of enzyme after the 106 week study period. Historically this has been done as part of a separate “continuation study” that all patients are automatically enrolled in.

Primary End Points – Decline or lack of decline in GMFC-MLD. Group A is expected to decline no more than 2 levels. Additional observations and tests will be for Expressive Language Function Classification in Metachromatic Leukodystrophy (ELFC-MLD), change from baseline in Cerebrospinal Fluid (CSF) sulfatides levels, etc.

Compassionate Use/Named Access – to the best of our knowledge no Compassionate Use or Named Access for SHP611 will be made for non-trial participants during the recruitment phase of this study.

Phase II Trial Time Frame – Takeda estimates the recruiting and two year study period will end in late 2022.

Development Timeline – This ERT has been in various stages of Clinical Trial since 2012.

Why is the Trial Targeted for Late Infantile MLD? Most MLD Clinical Trials target the late-infantile form of the disease because this form of the disease is the most rapidly progressing and hence it is easier and faster to show the efficacy of the enzyme therapy.

Access for Juveniles and Adults – It is Takeda’s desire, after drug approval, to make the ERT available to patients with all forms and stages of MLD where efficacy can be expected. Studying the ERT in late-infantiles is the fasted path to therapy approval by regulatory agencies (FDA, EMA, etc.) Please note, your treating doctor (not Takeda) may determine that your loved one is too advanced to see any benefit from the therapy.

ClinicalTrials.gov – Trial ID NCT03771898

Takeda Embolden Study Overview – Trial Overview provided by Takeda

Orphan Designation – SHP611 has Orphan designation by the EMA for Europe (EU/3/10/813).