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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
The December 1995 threshold event had the U.S. Food and Drug
Administration (FDA) approve porfimer sodium (PHOTOFRIN™) a
photosensitizing drug developed and patented by QLT PhotoTherapeutics
Inc. This application was designed to relieve symptoms of esophageal
cancer that is causing an obstruction and for esophageal cancer that
cannot be satisfactorily treated with lasers alone.
In January 1998, the FDA approved porfimer sodium for treatment of
early non-small cell lung cancers in patients for whom surgery and
radiotherapy are not options. The National Cancer Institute and other
institutions are supporting ongoing clinical trials to further evaluate the
use of PhotoDynamic therapy for other cancers. As well, research is
ongoing to find different laser types and new photosensitizers that might
increase the effectiveness of PDT against cancers located below the skin
or internal to an organ.
Esophageal Cancer
Estimated Annual Market @ US$30 Million
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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
Barrett’s esophagus
Estimated Annual Market @ US$40 Million
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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
Bladder cancer rates are relatively stable at about 17 per 100,000 in the
The potential PhotoDynamic United States with an estimated 54,400 new cases diagnosed in
Diagnosis and Therapy treatment 1998. Overall bladder cancer incidence is nearly four times higher in
market is in excess of US$7.25 men than women, and two times higher in whites than in African-
Billion annually. Americans; it is twice as prevalent in smokers as in non-smokers.
Since the 1970s mortality rates for bladder cancer have decreased for all
populations in the United States. There were an estimated 12,500
deaths due to bladder cancer in the U.S. for 1998. As with other forms
of cancer early detection is key to survival.
Treatment consists of surgery either alone or in conjunction with other
treatments. This is the method of choice in more than 90% of cases.
Preoperative chemotherapy or with radiation before cystectomy (bladder
removal) has improved treatment results. PhotoDynamic therapy clinical
trials are under way with prospective positive results. When diagnosed
at a localized stage the five-year relative survival rate is 94% and 74%
of cancers are detected this early. For regional and distant stages the
five-year relative survival rates fall to 49% and 6% respectively.
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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
Ophthalmology: (AMD)
(Age-related Macular Degeneration)
Currently the most closely watched
area within PDT is the treatment of Estimated Annual Market @US$1.75 Billion
Age-related Macular Degeneration –
Diseases of the eye caused by abnormal blood vessels and rapidly
the leading cause of blindness
amongst people aged 50 years or growing cells constitute a major health problem. AMD, diabetic
greater. retinopathy, glaucoma, secondary cataracts, neovascularization of the
cornea and iris, as well as intraocular tumors all have potentially serious
health consequences, with implications for a person’s ability to remain in
the workforce or in an independent living environment. AMD alone is
The only alternative treatment the leading cause of blindness in the elderly and may affect more than
currently available is hot laser 1.5% of the population over the age of 50 years. Some 200,000 new
photocoagulation. Collateral
cases are diagnosed annually in North America alone with
damage associated with this
additional 300,000 cases occurring worldwide. Although wet AMD
procedure in that not only is the
blood vessel sealed but the cells (degeneration due to leaking blood vessels) represents an estimated
immediately in the region are also 15% of all AMD cases, it accounts for 90% of severe vision loss
destroyed. This net result leaves associated with the disease. These estimates are expected to increase
the patient permanently blind at the dramatically as the baby boom generation ages.
location where the bleeding was
stemmed. Clinical trials just completed found that patients who underwent QLT’s
verteporfin therapy were more likely to have stable or improved vision
after 12 months than were people who received placebo injections
containing no medicine. These findings are based on results from 609
patients at 22 different medical centers. Overall, patients who received
PDT is the leading competing the therapy were 34% more likely to have stable or improved vision than
technology to redress this the placebo-treated patients, and the treatment appears to cause few
debilitating condition.
side effects. QLT’s second generation photosensitizer has the additional
advantage in that the post-treatment sensitivity to light is quite limited;
the patient is asked to avoid direct exposure to sunlight for a 24-hour
period. This contrasts sharply with historic therapies that left patients
sensitive to sunlight for as long as six weeks. Existing therapies are very
limited in their effectiveness and can lead to further vision loss insofar as
some form of collateral cellular destruction accompanies cauterization of
the leaking vessels.
Among those patients with AMD receiving QLT’s therapy, 16%
experienced improvement in vision of one or more lines on a standard
eye chart compared to 7% for patients receiving placebo. Statistically
significant results on the combined data favoring Visudyne™ therapy
were also obtained for all secondary test endpoints, including contrast
sensitivity and lesion growth. Results also showed that Visudyne
therapy was well tolerated, with less than 2% of patients withdrawing
from the study due to adverse effects.
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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
Lung Cancer
Estimated Annual Market @US$80 Million
Autoimmune Disease:
(Psoriasis, Rheumatoid Arthritis, Organ Transplant Rejection)
Estimated Annual Market @US$715 Million
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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
Breast Cancer
Estimated Annual Market @US$50 Million
PDT treatment of breast PDT investigations currently underway and in clinicals are focused on
cancer in women is metastasized breast cancer treatment modality that is immunotherapy in
complicated by the nature of concept. Cancer immunotherapy treatment is intended to produce
the cancer in that it typically tumor tissue destruction in the primary area of treatment. An important
evolves in small hard to detect distinction of cancer immunotherapy (echoed in the autoimmune disease
nodes, and possibly in more treatment protocols discussed above) is that this therapy is also intended
than one location. If detected to trigger an autoimmune reaction in the patient to complete the
early, the procedure is
destruction of the primary tumor and to concomitantly destroy any
relatively straightforward.
metastases. This approach is predicated on the appreciation that long-
term control or elimination of cancer of necessity requires the utilization
of the patient’s own immune surveillance and defense systems. An
optimal cancer treatment would be one that fully restores and stimulates
the body’s own immunobiological response to the growth of malignant
cells. PhotoDynamic therapy as in the treatment of both a metastasized
tumor and the collateral stimulation of the autoimmune system describes
some of the current efforts underway under the rubric of PDT
investigative work and associated clinicals. Pre-clinical work engaging a
photothermal response at the infrared end of the spectrum has gained
support from the FDA for the development of clinical plans to determine
an optimal approach to test the efficacy of the procedure.
Current aggressive treatments to mitigate metastic breast cancer include
the controversial bone marrow transplant procedure. This procedure
costs US$60,000 today, down from US$140,000 in 1990. PhotoDynamic
Therapy expenditures are likely to come in at less than an order of
magnitude lower; less than US$6,000.
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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
Cardiovascular Disease
Estimated Annual Market @US$3.5Billion
The coronary arteries supply a constant flow of oxygen-rich blood to the
heart, which pumps some 2000 gallons of blood throughout the body
each day. Arteriosclerosis results from the accumulation of cholesterol,
macrophages, and smooth muscle cells in the walls of blood vessels.
This often results in the narrowing of the lumen and reduction of blood
flow. In coronary arteries (vessels that supply the heart with blood),
arteriosclerosis can result in angina or heart attack. In the
Restenosis, or the
rehardening of arteries
cerebrovascular circulation (arteries supplying blood to the brain) such
post angioplasty, is an blockage can result in stroke. In the peripheral circulation (arteries
ideal condition to be supplying blood to the legs) atherosclerosis can result in ischemia
treated with PDT. leading to decreased function and ultimately loss of limbs. Currently,
atherosclerosis is treated with medical therapy, surgery or endovascular
Current advanced work procedures such as balloon angioplasty. In the U.S. some 600,000
demonstrates the ability of patients annually undergo coronary angioplasty to open or
the cells lining the interior remedy closed arteries due to accumulation of plaque on the inside walls
of the vascular wall to
of their arteries. Additionally another 150,000 such procedures are
recover their plasticity
consequently permitting
performed in the lower extremities. Typically 50% of all patients suffer
the conduit to function restenosis within six months of angioplasty treatments. Restenosis is the
normally. reclosing of blood vessels so treated. Clearly such reclosing or reversal
of the condition is a potentially life threatening condition for those so
afflicted. PhotoDynamic Therapy in the form of photoangioplasty holds
great promise due to the ability to deliver both photosensitizing drug and
light source to the typically local trouble focal point. In addition
photoangioplasty is a procedure which permits the flow of blood to
continue during the application, unlike the more traditional forms of
angioplasty. Drawing on the experience with the successful treatment of
psoriatic plaque on skin surfaces, current efforts are underway to further
develop therapeutic applications for reduction of atherosclerosis or
arterial restenosis utilizing the localized delivery of PhotoDynamic
therapy.
Cosmetic Applications
Estimated Annual Market@US$1.5 Billion
Hair removal and acne treatment have emerged as two secondary order
PDT is proving to find
applications from the research currently underway in a variety of sites
direct commercial and under a broad range of investigative protocols; all under the
cosmetology in treating: umbrella of PhotoDynamic technology application.
• Acne
PDT application for the removal of unwanted hair employing a
• Unwanted hair
• Surface psoriasis
photosensitive 5-ALA agent activated by laser generated light has
produced results to the extent that about 30% of the targeted hair was
prevented from regrowing after a one treatment application.
Similarly, small localized fluorescence employing 5-ALA, based on historic
knowledge of ALA activity in sebaceous (oil) glands, activated by a non-
laser red light achieved success in destroying the bacteria responsible for
acne lesions.
By extension, it is reasonable to intuit that PDT may find purchase as in
the treatment of a variety of indications that are medical in nature and of
serious cosmetic concern. The general utility of the treatment, its
viability as an outpatient protocol and the very fact of its non-toxic
repeatability and potential cost effectiveness may very well create a
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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
Investment Landscape
Non-pure play – Large pharmaceutical distribution and
marketing partners
Non-pure play: Established pharmaceutical giants have paired up with small research
Large biopharmaceuticals
and development biotechnology companies to keep pace with developing
engaged in marketing and
distribution
technologies in the unfolding noninvasive photosensitizer marketplace.
These include Novartis – CIBA Vision, Pharmacia – UpJohn, Sanofi
– Winthrop, Glaxo-Wellcome, American Home Products –
Cyanamid - Lerdele, Ligand, Hoechst-Celanese, and Beaufour
Ipsen. While it can be taken as a given that there may be some original
R&D taking place within these companies, only and Nippon
Petrochemicals seem to be actively engaged in original drug candidate
research. Mostly these multi-national pharmaceutical giants are taking
the deal making approach where they provide financing and/or
marketing distribution expertise and services on a royalty arrangement
with the biotechnology company. As for vehicles for equity investment,
none of the of the world’s leading pharmaceutical companies offers a
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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
Light Device
Therapy takes advantage of dye/drug phototoxicity and selectivity by
irradiating the suspect area with excitation light that induces the dye
Secondary partner play:
fluorescence. This technique depends on matching up wavelength with
Light delivery device manufacturers drug/dye and designing and developing the delivery mechanism. Both
“light amplification by stimulated emission of radiation” (laser) and non-
laser light excitation generators are employed. Determining the
potentiality of this device aspect of the PDT technology is the province
on the niche device developers and manufacturers. Of these Coherent,
Inc. (COHR) designs, manufactures and sells lasers, laser systems and
related accessories directly for the medical invasive, remedial and
cosmetic markets. Laserscope (LSCP), another specialty designer
and manufacturer is directly involved in developing and building
procedure and treatment lights and conveyance equipment, especially
for the PDT market. LSCP and COHR both received FDA approval in
1998 for their PDT LASER Systems for use with QLT’s Photofrin for
treatment in early-stage lung cancer and for late stage esophageal
cancer. LumaCare, a private company based in the U.K. has patented
technologies on non-coherent light sources for use at part of a PDT
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Light-activated Medicine - PhotoDynamic Therapy (PDT) February 2005
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