Microsoft word - type 1 clinical trials that target a practical cure

JUVENILE DIABETES CURE ALLIANCE

Peter Miselis, CFA Type 1 Diabetes Charitable Foundations
Director of Research Analysis
(646) 367-4497
[email protected] Update Report:
January 11, 2012 Type 1 Clinical Trials That Target a
Practical Cure
Organizations Mentioned:
• Very little of the research in human clinical trials has the potential to deliver a Practical Cure outcome for individuals living with fully established type 1 diabetes • From a list of 35 treatments that were selected because they investigate a cure for type 1 out of approximately three hundred projects, we believe that only five could meet the JDCA’s definition of a Practical Cure • Most of these 35 treatments have a fundamental improbability of delivering a Practical Cure outcome due to treatment design • The JDCA estimates that only an extremely small percentage of donor contributions to the four major type 1 foundations is used to fund research in clinical trials that has the potential to deliver a Practical Cure The JDCA and its employees seek to maintain independence from organizations covered in its research reports. The JDCA and its employees are free from conflicts of interest, receive no compensation from the organizations discussed in its reports, and seek to avoid any relationships with any organizations that could influence its objectivity and independence. Please see Analyst Certification and Other Disclosures at the end of this report This is the second in a series of reports that analyzes the type 1 diabetes (type 1) human clinical
trial landscape. Our most recent report, Type 1 Human Clinical Trials, examined 35 treatments
that are currently in clinical trials and were selected because they target a cure for type 1.1 This
report assesses the potential of those 35 treatments to deliver a Practical Cure and examines the
amount of donor contributions that are used to fund Practical Cure research that has advanced to
the human clinical trial stage. An analysis of the broader type 1 clinical trial landscape will be
the topic of a future report.
Exhibit A (on page 6) depicts 35 treatments in clinical trials that target a cure for type 1.
Clinical trials represent later stage research and are designed to assess the safety and efficacy of
treatments that have the potential to be clinically beneficial. Mr. Joshua Levy, who
independently monitors the type 1 cure research landscape, identified the 35 treatments which
satisfy his cure definition criteria.2 Exhibit A arrays the 35 treatments according to the basic
research approach, current phase of research (1, 2 or 3) and progress of the trial.

The JDCA’s definition of a Practical Cure that guides us in our mission to facilitate a cure
for those living with fully established type 1 by 2025 is as follows:
For at least 1 year, a cure must:
• Not require blood glucose monitoring beyond once a week • Not require carb counting • Not restrict a patient’s diet • Allow patients to sleep care free • Maintain A1c levels between 6-7 A cure must be delivered through a treatment that: • If it is surgical, requires a full recovery time of less than 72 hours. • If it is pharmacological, requires no more than a reasonable pill and/or injection regimen
A cure, which may include a drug regimen, must not have side effects or pose longer-term risks
greater than the current complications of Type 1.
In addition to the definition criteria listed above, the following factors are also considered
when evaluating treatments as potential Practical Cures:
A Practical Cure should be able to cure people already living with fully established type 1 Even if a treatment is being tested on just a subset of type 1 individuals, such as those newly diagnosed, if the treatment is designed to deliver a Practical Cure outcome for people with fully established type 1 it may be deemed a potential Practical Cure Treatments that rely on the interdependence of two or more drugs where the testing of that combination extends the delivery date beyond 2025 are not Practical Cures “Voice of the Donor for a Cure” Page 2 After individually examining the 35 treatments depicted in Exhibit A, we conclude that the
following five could meet the JDCA’s definition of a Practical Cure:
Diamyd/Sitagliptin/Lansoprazole (“D/S/L”)6
Each of these five can be categorized as either a beta cell encapsulation/transplantation
approach or a drug combination approach. Two of the five (DIABECELL and MCD) utilize
beta cell encapsulation and transplantation. This concept is straightforward: insulin-producing
islets are enclosed within a protective sheath or device and then implanted into an individual’s
abdomen. This involves a minor surgical procedure. The islets’ protective covering shields
them from an autoimmune attack, yet allows the secretion of insulin to regulate an individual’s
blood sugar levels. DIABECELL uses encapsulated porcine islets while the MCD encapsulates
human islets. Clinical trials for each involve testing individuals with established type 1.
The other three potential Practical Cures (ATG/GCSF, D/S/L and S/L) utilize a combination of
drugs that are designed to stop the autoimmune attack and to stimulate growth of beta cells. The
clinical trial for ATG/GCSF involves individuals that have been diagnosed with type 1 within the
past 4-24 months. Clinical trials for the drug combinations of D/S/L and S/L exclusively test
individuals that are newly diagnosed (in their honeymoon phase). Given the intended
mechanism of action of these drug combination treatments, the JDCA believes that if they cure
newly diagnosed individuals, they may also have relevance to established diabetics and are
potential Practical Cures.
Currently in Phase 2 clinical trials in two other countries and already approved in Russia,
DIABECELL is the most advanced in development among the five. We believe that all five
have the potential to meet a 2025 deadline by virtue of their already being in clinical trials.
Notwithstanding this potential, the JDCA cannot make a determination as to whether a
successful outcome will be achieved.

JDCA’s analysis of the 30 treatments depicted in Exhibit A that are not deemed to be
Practical Cures reveals that:
19 (63%) of the 30 exclusively target newly diagnosed individuals in their honeymoon phase---even if these treatments cure people in their honeymoon phase, the treatment would not extend to individuals with established type 1 and deliver a Practical Cure, in our opinion 17 of the 19 treatments that are oriented toward honeymooners are not potential Practical Cures because they target only the autoimmune attack and/or preservation of existing beta cell function---if successful, these treatments will only slow the progression or delay the onset of type 1. However, curing individuals with established type 1 requires a new source of beta cells or an agent to stimulate their growth along with a method to stave off the autoimmune attack. After many decades of research there is no evidence that natural beta cell regeneration alone in the absence of an autoimmune attack can restore normal glycemic control for established diabetics. We believe that if a potential Practical Cure “Voice of the Donor for a Cure” Page 3 with a known outcome is the goal of any type 1 research, natural beta cell regeneration
cannot be relied upon to restore normal glycemic control. Therefore, treatments that
target only autoimmunity have a fundamental improbability of curing individuals
with established type 1.
22 (73%) of the 30 treatments are prevention oriented---designed to delay the disease onset or prolong the honeymoon---but not designed to cure individuals with fully established type 1
The JDCA estimates that only an extremely small percentage of donor contributions to the
four major type 1 organizations that we cover is used to fund the clinical trials for the five
potential Practical Cures. We believe that only one of the four type 1 foundations that we
cover is funding the trials of any of these five potential Practical Cures; and this foundation is
only partially funding two of the five. The JDCA further believes that if the allocation of donor
contributions was aligned with the intentions of donors that contribute for the reason of a cure,
then significantly more funding would be directed toward Practical Cure research both in the pre-
clinical and human clinical trial stages of development.
Summary and Conclusion
From a list of 35 treatments that target a cure for type 1 out of approximately three hundred
projects, the JDCA believes that just five may have the potential to deliver a Practical Cure.1,2
Although we believe these five treatments, as designed, satisfy the JDCA’s Practical Cure
criteria, we cannot make a determination as to whether a successful outcome will be achieved.
Most of the cure treatments in clinical trials are oriented toward non-Practical Cure outcomes
such as prevention or they have a fundamental improbability of delivering a cure because they do
not address both autoimmunity and beta cell mass which is necessary to cure individuals with
fully established type 1. The small number (5) of treatments in human clinical trials capable of
delivering a Practical Cure is grossly misaligned with the primary motivation of type 1 donors
which is to develop a cure.8 The JDCA estimates that only a de minimis percentage of donor
contributions to the four major type 1 charities that we cover is used to fund clinical trials that
have the potential to result in a Practical Cure.
It is imperative that more resources be directed toward Practical Cure research in order to
increase the likelihood of delivering this outcome by 2025. Donors who contribute for the
reason of a cure have the ability to effectuate this change. The JDCA is hopeful that donors and
Alliance members who desire a Practical Cure will incentivize the type 1 charities they support
to fund Practical Cure research and to drive this research into clinical trials.
“Voice of the Donor for a Cure” Page 4 1 JDCA Type 1 Human Clinical Trials report dated December 14, 2011 2 Levy, J. (December 2011). Current Research into a Cure for Type -1 Diabetes. Retrieved from http://cureresearch4type1diabetes.blogspot.com/. Mr. Levy’s cure definition criteria include: Blood sugar control without testing and with doctor’s visits of four times a year or less Must result in an average lifespan close to normal Does not require a lifetime of harsh immunosuppressive drugs A couple of operations, or a short course of drugs is acceptable 3 Living Cell Technologies. Open-label investigation of the safety and effectiveness of DIABECELL(R)
in patients with type I diabetes mellitus. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National
Library of Medicine (US). 2000- [cited date]. Available from:
http://clinicaltrials.gov/ct2/show/NCT00940173?term=Diabecell&rank=1 NLM Identifier:
NCT00940173.
4 Cliniques universitaires Saint-Luc- Université Catholique de Louvain. Safety and efficacy study of
encapsulated human islets allotransplantation to treat type 1 diabetes. In: ClinicalTrials.gov [Internet].
Bethesda (MD): National Library of Medicine (US). 2000- [2011 Dec 2]. Available from:
http://clinicaltrials.gov/ct2/show/NCT00790257?term=Monolayer+diabetes&rank=1 NLM Identifier:
NCT00790257.
5 University of Florida. Reversing type 1 diabetes after it is established. In: ClinicalTrials.gov [Internet].
Bethesda (MD): National Library of Medicine (US). 2000- [2011 Dec 2]. Available from:
http://clinicaltrials.gov/ct2/show/NCT01106157?term=ATG+and+GCSF&rank=1 NLM Identifier:
NCT01106157.
6 National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Novel therapy combining
regenerative stimuli immunomodulation to preserve beta cell function in new onset type 1 diabetes. In:
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [2011 Dec 2].
Available from: http://clinicaltrials.gov/ct2/show/NCT00837759?term=sitagliptin+lanzoprazole&rank=2
NLM Identifier: NCT00837759.
7 Sanford Health. Combination Therapy With Sitagliptin and Lansoprazole to Restore Pancreatic Beta
Cell Function in Recent-Onset Type 1 Diabetes (REPAIR-T1D). In: ClinicalTrials.gov [Internet].
Bethesda (MD): National Library of Medicine (US). 2000- [2012 Jan 3]. Available from:
http://clinicaltrials.gov/ct2/show/NCT01155284?term=nct01155284&rank=1 NLM Identifier:
NCT01155284.
8 JDCA Why Donors Give report dated September 19, 2011

Analyst Certification
The JDCA analyst responsible for the content of this report certifies that with respect to each organization covered in this report:
1) the views expressed accurately reflect his own personal views about the organizations; and 2) no part of his compensation was,
is, or will be, directly or indirectly, related to the specific views expressed in this research report.
Other Disclosures
All Rights Reserved. The JDCA and its employees will not be liable for any claims or lawsuits from any third parties arising
from the use or distribution of this document. This report is for distribution only under such circumstances as may be permitted
by applicable law.
All information expressed in this document was obtained from sources believed to be reliable and in good faith, but no
representation or warranty, express or implied, is made as to its accuracy or completeness. All information and opinions are
current only as of the date of this report and are subject to change without notice
“Voice of the Donor for a Cure” Page 5 Exhibit A
Overview of Clinical Trials Aimed At Curing Type-1 Diabetes
Updated for October 2011
Clinical trials research studies done on people. They occur only after years of animal testing have established a basic level of safety and an expectation of success in people.
Because clinical trials take over 10 years to complete, this table offers a view into the future. Any possible cure for type-1 diabetes that will be available in the next ten year will need to be in clinical trials now.
Basic Approach
Notes on this Table
Has Started
Fully Enrolled
Published Results
This table was put together by Joshua Levy, who tracks all research which is in clinical trials and aimed at curing type-1 diabetes. Autoimmune Attack
Retrain the Immune P
http://cureresearch4type1diabetes.blogspot.com Encapsulated
Transplanted
Beta Cells
Combination Treatments:
Notes on Phases
Stopping Immune Attack
and Progress within Phases
& Regrowing Beta Cells
Beta Cell
Regeneration
Generally between 4 and 20 people, and lasts 1 to 4 years. Often not blind, and sometimes there is no untreated, or "placebo", comparison Phase-11
Inflammation
Generally 50-150 people, and lasts 2-4 years. Usually double blind.
Basic Approach P
Has Started
Fully Enrolled
Published Results
Phase-III
Generally 300+ people, and lasts 2-4 years. Usually double blind. Autoimmune Attack
The numbers and durations above are generally for type-1 diabetes. Different diseases have different requirements for the different phases Retrain the Immune
of clinical trials. For example, phase-III trials for type-1 drugs are usually about 300 people. However, phase-III trials of drugs aimed at Encapsulated
type-2 diabetes usually have more people enrolled.
Transplanted
Beta Cells
Combination Treatments:
Has Started
Stopping Immune Attack
This means that at least one patient has been accepted into the & Regrowing Beta Cells
(Some researchers mark this milestone when they start recruiting for Beta Cell
Regeneration
Fully Enrolled
The clincical trial has enrolled all the patients that it needs to complete. This is an important milestone, because once this has happened, it is possible to know when all the data for the study will Inflammation
be gathered. The trial design will include how long data need to be gathered. For example, if the last person joins in Oct. 2008 and the protocol is to gather data for 15 months, then the study will be "data Basic Approach P
Has Started
Fully Enrolled
Published Results
Published Results
Results for safety and effectiveness have been published, preferably Autoimmune Attack
Retrain the Immune
Encapsulated
Transplanted
Beta Cells
Combination Treatments:
Stopping Immune Attack
& Regrowing Beta Cells
Beta Cell
Regeneration
Inflammation
“Voice of the Donor for a Cure” Page 6

Source: http://www.thejdca.org/files/Type-1-Clinical-Trials-That-Target-a-Practical-Cure.pdf