The Circuitous Route by a Group of Novices to a New FDA Approved Cancer Therapy: HOW DID WE DO THIS?

85 Pages·2015·61.728 MB·English

by  PhD Thomas J. Dougherty

THE CIRCUITOUS
ROUTE BY A GROUP
OF NOVICES TO A
NEW FDA APPROVED
CANCER THERAPY
HOW DID WE DO THIS?
“THOMJ. ADSOUGHEPRHTDY,
The opinions expressed in this manuscript are solely the opinions of the author and do not represent the opinions or thoughts of the publisher. The author has
representedand warranted full ownership and/or legal right to publish all the materials in this book.
The Circuitous Route by a Group of Novicesto aNew FDA Approved CancerTherapy
HOW DID WE DO THIS?
All Rights Reserved.
Copyright © 2015 Thomas J. Dougherty, PhD
v1.0
Cover Photo © 2015 thinkstockphotos.com. All rights reserved - used with permission.
This book may not be reproduced, transmitted, or stored in whole or in part by any means, including graphic, electronic, or mechanical without the express written
consent of the publisher except in the case of brief quotations embodied in critical articles and reviews.
Outskirts Press, Inc.
http://www.outskirtspress.com
Outskirts Pressand the “OP” logo aretrademarks belonging to Outskirts Press,Inc.
PRINTED IN THE UNITED STATES OF AMERICA
3
outskirtspiess
DENVER, COLORADO
To my parents Joseph and Norma Dougherty
whoencouragedme to follow my dreams.
Author's Note:
How Naive can you get?
How did |ever think that someone with no background in medicine or biology, let alone cancer, could possibly develop a new cancer treatment?
Nonetheless, when |joined a cancer center in Buffalo following ten years in industry, |knew |could do this-NO DOUBT AT ALL! |had NO idea what |
was getting in to!
This book describes the ups and downs with the FDA, the lack of assistance and skepticism of scientific and medical staff at my institute and the
sometimes really offensive public comments from attendees at national and international scientific meetings even when |presented positive results
of our preliminary studies. Finally, with the help of the forward-looking and open-minded Chief of the Surgical Staff, anew cancer therapy came into
existence!
In 1970 in Buffalo, New York at a cancer center then known as Roswell Park Memorial Institute (later Roswell Park Cancer Institute), |found
—entirely by accident, that cancer cells could be destroyed when they were treated with a light absorbing drug and exposed to light. This eureka-
moment evolved into an obsession to create and make available to cancer patients, an effective new treatment based on this concept. This occurred
in 1973 when we treated our first patient with Photodynamic Therapy. This is process now referred to as Translational Research, taking a research
finding from the Benchto the Patient.This was the first time that this occurredat Roswell Parkso we hadto figure out how to do it on our own!
Serendipity, or what some might call “dumb luck,” has been a constant companion in my professional life, and |owe “him/her/it" at least a few
knowing nods of acknowledgment.
|like to think of myself as an accidental pioneer, whose brush with serendipity led him on an exciting and sometimes frustrating quest through
challenging terrain, often without benefit of a reliable guide. This odyssey, fraught with detours and dead ends, steep hills and learning curves—was
a testament to the famous axiom of Murphy's Law: Whatever can go wrong, will. Still, there is no doubt that while PDT came about as a result of an
unbelievable series of unplanned and unexpected events, |can say without reservation that every step and corresponding misstep were, in the long
run, steps in the right direction.
|recently came across a definition of serendipity that |feel best captures the essence of this great adventure: “if your heart is open, if it is free of
meanness, destiny takes us to wonderful places.” (1)
This is my story—a travelogue of sorts—of the development of PDT, the quarter-century journey to obtain FDA approval and the wonderful
places destiny has taken me. My narrative here ends ona satisfying, although not definitive, note. There’s certainly much more to be written and
logged by the next generation of PDT explorers and innovators. More importantly, the genuinely happy endings exist in the countless unpublished
sidebar stories of cancer patients who have benefitted—and will continue to benefit—from this treatment.
While there are many people to thank, |would like to especially recognize three important players in this saga: Pastor Nathaniel Preisinger of the
Parkside Lutheran Church in Buffalo, who unknowingly gave me the extra push |needed to share my story; the late Arnold Mittelman, MD, of Roswell
Park Cancer Institute, one of the true heroes and visionaries behind PDT’s advancement; and Yosihiro Hayata, MD, of the Tokyo Medical School in
Japan, who elucidated, early on, some of the most effective applications of this treatment. In no small measure,their friendship and faith in me helped
illuminate the way, and |am most humble and grateful for their support.
Thomas J. Dougherty, PhD
Buffalo, NY
(1) White, Randy Wayne. Gone (A Hannah Smith Novel). New York: G.P. Putnam’s Sons, 2012.
Contents
Prologue
Chapter 1: Let There Be Light: Photodynamic Therapy
Chapter 2: Life Before PDT
Chapter 3: Photochemistry & Librettos: The DuPont Years (1960-1970)
Chapter 4: ACancer Researcher at Home...and Abroad
Chapter 5: Seeking Federal Funding: My First Grant Application
Chapter 6: OT Mice and Men: Success from a Failed Experiment
Chapter 7: Hematoporphyrin Derivative: (HpD) as aPDT Agent?
Chapter 8: Running Interference: A Clash of Opinions? /
Chapter 9: "Elegant But Impossible”: The Best Backhanded Compliment |Ever Received
Chapter 10: New Directions, New Staff and Graduate Students: The PDT Program Expands
Chapter 11: Preparing for Clinical Studies
Chapter 12: Lesson 1: AMouse Is Not aHuman
Chapter 13: Buffalo, We Have a Problem!—The FDA Sets Us Straight
Chapter 14: The Dog (and Cat) and Pony Show: Pet Projects
Chapter 15: Launch of the First PDT Company: We Will Need Money
Chapter 16: From HpD to Photofrin-A Patent?
Chapter 17: Expanding the Applications of PDT: The Japanese Connection
Chapter 18: The Trip to China
Chapter 19: Patents and Patience
Chapter 20: The Big Leagues: Partnering with Jonnson & Johnson
Chapter 21: The Oncologic Foundation of Buffalo
Chapter 22: 1990: J&J Drops aBomb
Chapter 24: Search and Rescue: Is Anybody Out There?
Chapter 24: The Holy Grail: Our First US-FDA Approval
Chapter 25: HPPH: Our New Photosensitizer (HPPH)
Chapter 26: Licensing HPPH: Here We Go Again!
Chapter 27: Light at the End of the Tunnel: Photolitec
Chapter 28: Expanding PDT to New Cancer Applications and Developing a PDT Induced Cancer Vaccine
Epilogue
Acknowledgments
Prologue
“The harder|work, the luckier |get.”
~Samuel Goldwyn
Before commercialization of any new medical treatment or technology, certain national standards must be met: promising basic and clinical research
must be conducted, extensive safety and efficacy testing must be done, and finally—and what may be the most challenging hurdle—approval must be
granted by the US Federal Drug Administration (FDA) which, as the reader will discover from the experiences detailed in this book, is no hop, skip and
a jump to the public marketplace. FDA approval is the culmination of years, sometimes decades, of intense research and teamwork—demanding of
researchers the patience of Job and the unwavering belief that they have something important to contribute that would ultimately make a difference
in the lives of patients.
In 1994, more than 20 years after the start of its development, Photodynamic Therapy (PDT) received its first FDA approval for the palliative
treatment of advanced esophageal cancer. PDT is a targeted cancer treatment, which means that it “targets” only tumor cells for destruction without
permanently damaging surrounding tissue.
The treatment combines a nontoxic photosensitive drug that accumulates in tumor tissue, with a red laser light that destroys the tumor. Because
PDT is classified by the FDA as a “dual treatment”—using both a drug (a photosensitizer) and a device (a laser) to work—two separate FDA approvals
are required. Photofrin, the photosensitizer that we developed at Roswell Park Cancer Institute, is the PDT drug that has been approved by the FDA
to treat or relieve the symptoms of certain types of cancers, including late-stage esophageal cancer, Barrett's esophagus (a pre-cancerous tissue), and
early-stage and advanced lung cancer.These approvals indicate that the FDA considers PDT to be both safe and effective for these specific types of
diseases
Photofrin-based PDT is also available as an “off-label” treatment for many other types of cancer, including those of the skin, lung, breast, the
female reproductive system, esophagus, pleura, head and neck. Off-label means that while a treatment may be approved by the FDA for one type of
cancer, it may be used, based on strong evidence reported in peer-reviewed medical journals, for a different type of cancer without FDA approval or
data from clinical studies. There is adownside to pursuing this avenue. A treating physician can risk a lawsuit if something goes wrong and may have
diticulty receiving reimbursement trom insurance companies.
Over the years, PDT has also been approved by national agencies in many countries for specific types of cancer—in Canada, for bladder and
esophageal cancer; in The Netherlands, for lung and esophageal cancer; in Japan and Germany, for early-stage lung cancer; and in France, for early-
and late-stage lung cancer.
This book tracks my experience with the long and arduous—and often, serendipitous—process involved in garnering FDA approval for PDT-
necessary to make the treatment available to cancer patients.
CHAPTER T
Let There Be Light:
Photodynamic Therapy
What is photodynamic therapy (PDT)?
As a cancer treatment, PDT requiresthe combined eftect of three essentials: oxygen, a light-absorbing drug called a photosensitizer, and a tissue-
penetrating light source.
Here's how it works: A photosensitizer, injected into the bloodstream, is taken up by both normal and cancerous tissue. Within 24 to 72 hours,
it concentrates in the tumor tissue at higher levels than in the normal tissue. The tumor is then exposed to red laser light delivered through fiber
optics. The drug absorbs the light, becomes “excited” (excess energy), transfers the excess energy to the oxygen in the tissue converting it into a highly
reactive form of oxygen that attacks the tumor and under ideal conditions, shrinks or destroys the tumor (See photos below). The photodynamic
cancer treatments that have been approved by the FDA use the photosensitizer Photofrin® that was developed in my laboratory at Roswell Park
CancerInstitute beginningin 1970.
pee
sitizer
Sequenceof PhotodynamicTherapy