Updates
Winter 2011

from the Faustman Laboratory at Massachusetts General HospitalMoving Forward into Phase II
A Note from Dr. FaustmanAs year end approaches andwe begin planning the Phase
II human clinical trial in type 1
diabetes, it’s a nice time to lookback at all of our progress.
We’ve come a long way since2001, when we first announced
we could reverse type 1
diabetes—in mice. Today, all of
our type 1 diabetes work is in
humans. In fact, we no longer
even have mice at the lab! Our
success, which includes bringing
a generic drug successfully
through Phase I testing, is thefruition of over 20 years of
research—research that hashelped to redefine how we look at
the treatment of this disease.
One of the things that makes
our trials so unique is that we are
testing a new treatment approachfor people who have been
diabetic for many years. This isunlike other type 1 diabetes trials,
which tend to look at ways toprevent or delay type 1 diabetes,or to focus only on those whohave just been diagnosed. While
necessary, those trials leave out awhole population of people whohave been living with the disease
for a long time.

In our studies, we are trying
to address one of the underlying
causes of type 1 diabetes: theautoimmune attack on thepancreas. In our experiments in
end-stage diabetic mice, stopping
this attack allowed the pancreas
to regenerate and restored blood
sugars to normal, even in lateWe also want the treatment tostage disease.
be affordable for patients here
This approach also seems toin the U.S. and worldwide. This
work in humans. As we saw in the is why we are so happy to findPhase I BCG trial, participants
such a promising generic drug
began to briefly produce small
to test in these studies. If ouramounts of insulin when wetrials demonstrate that BCG isinterrupted the autoimmune
an effective diabetes treatment,
attack. In Phase II, we will work
we hope that its approval would
to refine our dosing and identify not only have a tremendous
how frequently patients would
impact on the health of people
need to be treated to sustain
living with type 1 diabetes, butthese effects.
also reduce diabetes-related
We hope that our efforts will
healthcare costs, which are sotranslate into a treatment thatburdensome on families.
can put type 1 diabetes into
Thank you so much forremission, sparing people withsupporting these human clinicaltype 1 diabetes the need to sotrials to reverse diabetes! Happyfrequently monitor glucose levels Holidays!
or administer insulin—also
better protecting them against
Sincerely,
dangerous fluctuations inblood glucose levels that cause
both short- and long-term
complications.
Denise L. Faustman, MD, PhD

UpdateWinter 2011

Phase I Success
BCG Vaccination Eliminates
Defective T Cells, Briefly Turns
Pancreas Back On
This summer, new data from thePhase I BCG Human Clinical Trial
was presented at the American
Diabetes Association’s annual
scientific conference. This trial,
which is part of the Cure Diabetes
Now program at Massachusetts
General Hospital, was the first stepin testing the inexpensive genericdrug BCG (Bacillus CalmetteGuérin) as a treatment foradvanced type 1 diabetes.
The Phase I data showed thatstudy participants—who had been
living with type 1 diabetes for 15
years, on average—had positive
responses to BCG treatment,even at relatively low doses.
In the study, we saw that BCG
treatment could eliminate thedisease-causing T cells (the ones
that attack and kill the insulinsecreting cells of the pancreas).
We also saw early signs that thepancreas was starting to produce
insulin again—at least briefly—
after years of dormancy in those

who received treatment.
Together, these data show thepotential of BCG treatment or asimilar therapy to turn the pancreas“back on”, even in people whohave had type 1 diabetes for morethan a decade. This exciting news
was covered in media outlets fromThe Wall Street Journal to the Los
Angeles Times.
The Phase I safety data, releasedin June 2010, had previously
shown that there were no serious
or unexpected adverse effects
from low-dose, repeated BCG
vaccination (two vaccinations
spaced four weeks apart).
A Phase II study will be
conducted to both expand onthese findings in a larger group ofpatients and to identify the drug
dose and schedule needed tomaintain a sustained response.

Phase II Study Kicks Off$8.5 Million Raised
The first fundraising goal for thePhase II trial was met this summer:$8.5 million, or one-third of theneeded funding, which is enoughto support the first year of work.

Faustman Lab in the News!
The results of the Phase I trial were featured in many news outlets
this summer, including The Wall Street Journal (“Drug Offers Hope inDiabetes Study”), the Los Angeles Times (“Research Shows Promise in
Reversing Type 1 Diabetes”), United Press International (“Cure for Type
1 Diabetes?”), and Bloomberg (“Generic Tuberculosis Medicine Shows
Promise for Reversing Type 1 Diabetes”). Want to read more?
Please visit our website www.faustmanlab.org and click on “News.”

Early work is now underway.
In the Phase II study, which
will include a larger number ofparticipants than Phase I, we will
look for the optimal dose of BCG
and investigate how frequently
it would need to be given to bea functional and sustained type1 diabetes treatment—one thathalts the autoimmune attackon the pancreas and, hopefully,
allows some level of insulin
production to begin again, as we
saw in the Phase I study.
Our trial team has begun
taking many of the required
steps that will lead up to patient
enrollment. Some of the key
steps include: working on trial
design, submitting regulatory
documents to the FDA, setting up
a data safety monitoring board,
determining the criteria forpatient selection, further refining
the methods for monitoring drug
efficacy, and identifying which
outcome measures will be used
to determine whether the trial
is a success. With these steps inplace—along with the funds tosupport the study beyond year
one—patient enrollment may
begin as early as the end of 2012.

www.faustmanlab.org

Building Better Tools
New Machinery for Clinical
Trial Monitoring
In type 1 diabetes, a defective
subpopulation of white blood
cells is responsible for mistakenly
attacking and destroying thepancreatic cells that produce
insulin. The ability to easily isolate
and count these “bad” white blood
cells in a given blood sample isimportant for type 1 diabetes
research. With this ability, we cansee whether the treatments we are
testing in clinical trials specificallyeliminate the unwanted cells.
For this reason, designing andbuilding better tools for whiteblood cell isolation has been amajor focus in our lab since 2003.
To achieve this, we assembled aninterdisciplinary team of biologists
and engineers to design and build
cell isolation machinery. We thenextensively tested the machineryto show that it was more accurate
and precise than existing methodsof separating white blood cells forresearch. We also automated thetechnology so that the process
would be efficient.
This year, we shared a detailed
description of this machinery withthe larger scientific community in
our paper, “Novel Automated Blood
Separations Validate Whole Cell

Biomarkers,” which was publishedin the online journal PLoS ONE.
This is the same machinery
we used in the Phase I study
to monitor the effects of BCG
vaccination on the “bad” whiteblood cells in people with type1 diabetes. With it, we were able
to see, week by week, that BCG
treatment selectively killed thedefective white blood cells.
This technology will continue tobe instrumental as we move into
the Phase II human clinical trial
and look at different doses of BCG,
different intervals between doses,
and different patient groups with
type 1 diabetes.

AwardsDr. Faustman Honored
at “Laughter Is the Best
Medicine” Event
This summer, Dr. Faustman
was honored by Partnership forCures with the “2011 George andJudith Goldman Angel Award” forher research to find an effective
treatment for type 1 diabetes
using a generic drug.
The award was presented at thePartnership for Cures “Laughter
Is the Best Medicine” event.
Partnership for Cures and its
funding partners are longtime
supporters of the Faustman Lab’s
research.
Dr. Denise Faustman with Partnership for Cures President, Dr. Bruce Bloom, atthe “Laughter Is the Best Medicine” event.

UpdateWinter 2011

Leadership Role for Iacocca Foundation
Foundation Resumes Commitment to BCG Clinical
Trial Program
The Iacocca Foundation, which played a key role in helping
to fund the Phase I study, has committed to a leadership role for
the Phase II clinical trial. The renewed commitment from the
Iacocca Foundation, along with the support of other philanthropic
organizations and donations from thousands of individual
supporters, has helped the Faustman Lab raise over $8.5 million for
the Phase II trial to date.
The Iacocca Foundation is also calling on other donors to help
raise the total $25.2 million needed to fully fund the Phase IIprogram.
“We have supported this work since the mouse studies thatfirst showed the reversal of longstanding diabetes. The Iacocca
Foundation has made a significant gift to the MGH to help start thePhase II trial and we hope that others will join us,” said Kathryn
Iacocca Hentz, President of the Iacocca Foundation.

About the Type 1 Diabetes Reversal Trials at MGH
Led by Dr. Denise Faustman at Massachusetts General
Hospital (MGH), the BCG Human Clinical Trial Program istesting Bacillus Calmette-Guérin (BCG), an inexpensive genericdrug, as a treatment for advanced type 1 diabetes. In the
recently completed Phase I study, BCG was administered toadults who had been living with type 1 diabetes for an averageof 15 years. This treatment not only helped eliminate thedefective T cells that mistakenly attack and destroy the insulinproducing cells of the pancreas, it also temporarily restored theability of the pancreas to produce small amounts of insulin.
The next step, a Phase II study, is currently being planned, withthe goal of identifying the drug dose and schedule that will put
advanced type 1 diabetes into remission.

Looking for more information about this type 1 diabetes research?
Please visit www.faustmanlab.org.
Have questions about participating in future studies?
Please email: DiabetesTrial@partners.org.

How You Can Help
Please consider making a taxdeductible donation today tosustain the momentum of this type1 diabetes research program. Every
gift makes a difference for patients… today and tomorrow.
1. To make a secure online
donation, please visit
www.faustmanlab.org andclick on “Support.”
2. You may make a gift by check(**payable to “Massachusetts
General Hospital”**) and mailyour check to:
Diabetes Clinical Trial
c/o Dr. Denise Faustman
Immunobiology Laboratory
Massachusetts General
Hospital-East
Building 149, 13th Street, CNY-3601
Charlestown, MA 02129

On the memo line of your check,please write: “Type 1 diabetes
research.”Thank you for joining us in thefight against diabetes!

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