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A Report: NPC Drug Trials

Three NPC drug trials are currently ongoing – Vtesse, Orphazyme, and the NIH are evaluating different treatments for NPC. However, not all drugs are created equal, and after careful evaluation of each trial, Vtesse's effort with VTS-270 – cyclodextrin – clearly outstrips the alternatives. Read on to find out about the contrasts between these three trials.

Disclaimer: The views and opinions expressed in this page are those of Fight NPC and do not necessarily reflect the views of the families and doctors featured on Fight NPC.

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1. Vtesse's VTS-270 (Cyclodextrin)
Score: 8.3 / 10 (Highest Rated)

Built on a strong backbone of published and independently verified data in humans, cats, mice and in vitro, the Vtesse trial for VTS-270 (cyclodextrin) has by far the most and the strongest data of any of the three NPC drug trials.

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Untreated NPC Cat – Falls Over

This cat shows tremor (+3), ataxia (+4) and inability to stand without support. (Age: 21 weeks.)6

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Treated With VTS-270 – Cat Appears Normal

This cat, having received "IT" injections of VTS-270 (cyclodextrin) every 2 weeks since 3 weeks of age, appears neurologically normal. (Age: 24 weeks.)7

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The data provides a strong foundation for confidence.

Animal Models

Cats and mice treated with VTS-270 lived longer and had reduced symptoms of NPC.

Humans

For the Phase I trial and the Rush iIND patients, most symptoms of NPC progression seemed to slow, stabilize or even improve after receiving VTS-270 treatment.

FDA Breakthrough Therapy

The FDA granted Breakthrough Therapy status to VTS-270 based on preliminary clinical data in humans showing that VTS-270 may demonstrate substantial improvement over existing therapies.

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VTS-270 treatment is sometimes difficult, but brings results.

Travel

Although patients must go to the clinical site every two weeks, Vtesse's travel agent will coordinate travel bookings and reimburse travel expenses.

Lumbar Puncture

While it may cause some anxiety, many clinicians are experienced in giving drugs intrathecally (ie. via a lumbar puncture), and a number of NPC patients have already undergone the procedure and found it to be only a minor difficulty.

Hearing Loss

The main adverse effect of VTS-270 so far is hearing loss, but for Phase I trial patients it has been manageable.

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2. Orphazyme's Arimoclomol
Score: 1.7 / 10

A potential therapy for NPC with little published data and even less independently verified data, Orphazyme's arimoclomol small molecule may prove to be of great benefit to the NPC community, but for now its benefits remain largely unproven.

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An easy option with little supporting data.

Easy

Arimoclomol is orally administered (capsule) at home.

Unpublished

No animal model data for arimoclomol has been published.

Not Independently Verified

Data for arimoclomol from animal models has not been independently verified by another lab.

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3. NIH's Vorinostat
Score: 1.5 / 10

A cancer drug re-purposed for NPC, there has been limited basic research done for Vorinostat as an NPC treatment. This drug might prove beneficial to NPC patients in the future, but at present it is a drug that is primarily being tested for safety.

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An adults-only safety trial to repurpose Vorinostat for NPC.

Cancer Drug

Through the use of high-throughput screening, researchers at the NIH discovered that Vorinostat, an HDAC inhibitor used to treat cancer, has potential to treat NPC.

Adult Patients

The Vorinostat trial is for patients 18 years and older.

Safety Trial

The primary purpose of the trial is to determine whether or not the drug is safe in NPC patients, not to demonstrate effectiveness.

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How the Trials Are Scored

The Data – The factor that contributes the most weight to each drug trial's score is the amount of data and the quality of data showing that the drug is likely to a) prolong life and b) improve quality of life in NPC patients. Data is weighted in the following order, from most indicative of human benefit to least:
  • Data from humans
  • Data from large animals (e.g. cats)
  • Data from small animals (e.g. mice)
  • In vitro data (e.g. cell cultures)
Other Factors – A drug trial's score is lowered if the trial has a control group, if the trial is difficult to participate in, or the drug is difficult to administer. A drug trial's score is raised if there is data for this drug from another disease or if the FDA granted the drug Breakthrough Therapy status.

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A Detailed Explanation

The Data
  • Benefits Score = a number between 0 and 1; if the expected benefit is both prolonged life and improved quality of life, it's a 1.0; if the expected benefit is only one or the other, 0.75; if the expected benefit is uncertain, 0.5.
  • Data Weight = 2 for in vitro models, 2 for small animal models, 2 for large animal models, and 4 for humans.
  • Data Quality = a number between 0 and 1; the more published papers and the more independent verification of the drug, the closer the score is to 1.0.
  • Data Weight x Data Quality = multiply the data quality by the data weight for one type of data (e.g. in vitro).
  • Sum of (DW x DQ) = the sum of Data Weight x Data Quality for all types of data (ie. in vitro, small animal model, large animal model, & humans).
Other Factors
  • FDA Breakthrough Bonus = a number between 0 and 1; if the drug was granted FDA Breakthrough Therapy status, then a bonus of 1.0 is scored.
  • Other Disease Bonus = a number between 0 and 0.5; if the drug was tested for another disease and was safe, then a bonus of 0.5 is scored.
  • Difficulty Penalty = a number between 0 and 1; if the drug is easy to use, then 0 points are removed; if the drug is difficult to use, then a penalty of 1.0 is assessed.
  • Control Group Penalty = a number between 0 and 1; if the drug has no control group, then a factor of 1.0 is used as a multiplier; if the trial has a 2:1 ratio active:control, then a factor of 0.83 is used as a multiplier (a penalty of 1/6th).

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NPC Drug Trials: Side by Side

VTS-270 (Cyclodextrin)
Vtesse, Inc.

Overall Trial Score: 8.3/10

Anticipated Results in Humans

Prolongs Life
2x Longer in Mice1, 8x Longer in Cats2
Improves Quality of Life
Speech, Swallowing, Cognition, Memory, Fine Motor Skills & Walking3

Data From

In Vitro
Small Animal Model (eg. mouse)
Large Animal Model (eg. cat)
Humans

Data

Has Been Published
Has Been Independently Verified
Approximate Number of Published Papers
50 or more4,13

Other Data

FDA Breakthrough Therapy
Status Granted by FDA5
Compassionate Use / iINDs
~20 patients already use cyclodextrin to treat NPC8
For Other Diseases
n/a

Trial Information

Phase of Trial
Phase II/III
Purpose of Trial
Pivotal Trial
Route of Administration
Lumbar Puncture (Intrathecal Injection)
Age Range
4-21
NPC Type
NPC1
Masking Type & Ratio of Active:Control
Active Intervention vs. Sham (2:1)
Frequency of Administration & Duration of Trial
Every 14 days, For 12 months
Rescue Option
Open for Enrollment

Arimoclomol
Orphazyme ApS

Overall Trial Score: 1.7/10

Anticipated Results in Humans

Prolongs Life
Improves Quality of Life

Data From

In Vitro
Small Animal Model (eg. mouse)
(not published)9
Large Animal Model (eg. cat)
Humans

Data

Has Been Published
In vitro only9
Has Been Independently Verified
Approximate Number of Published Papers
3 or more10,14,15

Other Data

FDA Breakthrough Therapy
Videos
Compassionate Use / iINDs
n/a
For Other Diseases
Arimoclomol was previously used in a Phase II trial for ALS11

Trial Information

Phase of Trial
Phase II/III
Purpose of Trial
Pivotal Trial
Route of Administration
Oral Therapy (Capsule)
Age Range
2-18
NPC Type
NPC1, NPC2
Masking Type & Ratio of Active:Control
Active Intervention vs. Placebo (2:1)
Frequency of Administration & Duration of Trial
3x/day and 5-7 Office Visits (Exams), For 12-18 months
Rescue Option
Open for Enrollment

Vorinostat
NIH

Overall Trial Score: 1.5/10

Anticipated Results in Humans

Prolongs Life
?
Improves Quality of Life
?

Data From

In Vitro
Small Animal Model (eg. mouse)
Large Animal Model (eg. cat)
Humans

Data

Has Been Published
Has Been Independently Verified
Approximate Number of Published Papers
5 or more16

Other Data

FDA Breakthrough Therapy
Videos
Compassionate Use / iINDs
n/a
For Other Diseases
Vorinostat is already licensed as a cancer drug (for cutaneous T-cell lymphoma)12

Trial Information

Phase of Trial
Phase I
Purpose of Trial
Safety & Tolerability
Route of Administration
Oral Therapy (Capsule)
Age Range
18-60
NPC Type
NPC1, NPC2
Masking Type & Ratio of Active:Control
None (Open Label)
Frequency of Administration & Duration of Trial
3 Days On, 4 Days Off, For 3 Months (With Evaluation at 6 Months)
Rescue Option
n/a
Open for Enrollment