“Angiogenesis 2007” Meeting Highlights
Avastin Used to Treat ROP.
JACLYN KOVACH, MD, MEDICAL RETINA FELLOW, BASCOMPALMER EYE INSTITUTE
Small studies conducted by
researchers in Mexico and Portugal
strongly suggest that intravitreal injections
of the Genentech drug Avastin
can be used effectively to treat
retinopathy of prematurity (ROP).
A case study based on this research
was reported by retina specialists from
Bascom Palmer Eye Institute in the
January/February 2007 issue of
Retinal Physician (“Bevacizumab for
salvage therapy in threshold retinopathy
Data from the 2 new studies was
among the highlights of the
“Angiogenesis 2007” meeting recently
conducted by Bascom Palmer. The
meeting also highlighted other new
research in ocular angiogenesis, drug
development for the treatment of
numerous debilitating retinal diseases,
and the economic impact of new retinal
drugs on Medicare.
The first Avastin for ROP study
involved a series of 18 eyes of
13 patients from Mexico City. Hugo
Quiroz-Mercado,MD, reported the
efficacy of Avastin in infants with
varying degrees of ROP. He reported
that 17 of 18 patients improved without
further sequelae and 1 patient
required vitrectomy. Susan Texeira,
MD, of Lisbon, Portugal, reported on
a series of 6 eyes injected as salvage
therapy, either as monotherapy or in
addition to laser therapy. All injected
eyes improved, with none requiring
additional treatment. No local or systemic
adverse events were noted in
either study.While both physicians
were optimistic about early results,
they cautioned that further controlled
studies are needed to determine the
safety and efficacy of VEGF-inhibiting
Avastin in the still-developing
eyes of infants.
The positive results from the small
studies has led to announcement of a
trial of Avastin for advanced ROP.
This study will be a multicenter, randomized
prospective controlled clinical
trial of 110 patients. Enrollment is
expected to begin this summer.
In additional discussion of ROP,
Lois Smith,MD, PhD, and Emily
Chew,MD, emphasized the importance
of omega-3 fatty acids in preventing
neovascularization, both in
models of ROP and neovascular
AMD as reported from AREDS.
Michael Trese,MD, emphasized the
role of VEGF in ROP and the importance
of timing anti-VEGF treatment.
Gerald Lutty, PhD, discussed the drug
VEGF Trap in a dog model of ROP
that showed that inhibition of VEGF
blocked preretinal neovascularization.
He reported inhibition of normal retinal
development at high doses, but
lower doses did not appear to be
In another presentation,
Jayakrishna Ambati,MD, and Cedric
Francois,MD, PhD, explored the use
of complement inhibition for the
treatment or prevention of AMD.
Dr. Ambati emphasized inhibition of
C3a and C3b receptors. He also discussed
a drug from Quark Biotech, a
small interfering RNA (siRNA) molecule
that inhibits choroidal neovascularization.
Other promising treatments discussed
included the topical antioxidant
OT-551 being developed by
Othera Corp. for the treatment of
geographic atrophy and an endothelial
nicotinic acetylcholine receptor agonist
known as mecamlyamine from
CoMentis (formerly known as
Athenagen) that inhibits angiogenesis.
Researchers agree that now is an
exciting time for diseases involving
ocular angiogenesis, with a number of
new therapeutics now available to
temper the activity. ROP is a particularly
fascinating disease to researchers
because modulation of angiogenesis
during a crucial time window may
provide a definitive cure to those with
an entire future before them.
Angiogenesis 2007 also featured a
number of presentations focusing on
the efficacy and safety of Lucentis and
Avastin in the treatment of choroidal
neovascularization and macular
edema. In all of the studies discussed,
improvements in visual acuity and
macular anatomy were achieved.
William Rich III,MD, and George
Williams,MD, discussed healthcare
economics as they relate to the new
treatment paradigm for wet AMD. In
addition to the role that basic research
and clinical trials will play in retinal
disease therapy, they asserted that the
future of clinical practice in retina will
undoubtedly feel the pressure of cost
OSI Plans Eyecare Exit
CEO: Macugen and Patents for Sale.
Calling his company’s 2005 entrance into eyecare “a major misstep,”OSI Pharmaceuticals’ CEO Colin Goddard, PhD, recently updated OSI’s progress in exiting the eyecare business. Sales of Macugen, OSI’s treatment for wet AMD, have declined sharply since the more efficacious Genentech drug Lucentis was approved by the FDA last June. Macugen worldwide sales totaled $10 million for first quarter 2007 after topping out at $50.5 million in the first quarter of last year. This resulted in a loss of approximately $13 million in the quarter for the eyecare business, which OSI now reports as a “discontinued operation.” OSI’s 3-pronged strategy for exiting eyecare calls for:
▪ simplifying OSI’s agreement with its marketing partner Pfizer, thus making it easier for a potential eyecare buyer to structure a deal
▪ reducing Macugen-related staff and expenses to conserve cash until a deal is completed
▪ holding discussions with companies and venture-capital entities that express an interest in ownership of Macugen and/or related patents The first element of the exit strategy has already been achieved. OSI has reached an amended agreement with Pfizer that calls for OSI to have exclusive rights to develop and commercialize Macugen in the United States, while Pfizer has similar rights for the rest of the world. The previous agreement had included a number of provisions for granting licenses, sublicenses, and patents. In regard to conserving cash, Dr.Goddard said the New York headquarters of Eyetech Pharmaceuticals, the original developer of Macugen, had been closed and all remaining Macugenrelated staff moved to an OSI facility in New Jersey. Dr.Goddard said OSI is currently spending about $3 million a month supporting Macugen. Dr. Goddard expressed confidence that Macugen and related eyecare patents would be sold in 2007, with the possibility that there will be a buyer for Macugen and another buyer for the patents. He said that “multiple parties” had expressed interest in the drug and/or the patents. Dr. Goddard said the key phase 4 LEVEL study, which uses Macugen as maintenance therapy after initial treatment with Lucentis, would go forward. He noted that Macugen has an excellent safety record and that safety data could be a factor in increasing the future value of the Macugen franchise. OSI spent approximately $650 million to acquire Eyetech in 2005 but has now written off almost all of its initial investment.
Potentia AMD drug. Potentia Pharmaceuticals, Inc., said it is about to begin a phase 1 trial as part of the development for POT-4, its lead drug candidate for the treatment of both the wet and dry forms of AMD. Fifteen to 18 patients with late-stage AMD will receive intravitreal injections of the drug, with treatment starting as early as this summer. Potentia describes POT-4 as a synthetic peptide discovered by John Lambris, PhD, of the University of Pennsylvania. It binds tightly to complement component C3, preventing its participation in the complement activation cascade. “As C3 is the central component of all major complement activation pathways, its inhibition effectively shuts down all downstream complement activation that could otherwise lead to local inflammation, tissue damage, and upregulation of angiogenic factors such as vascular endothelial growth factor,” says Cedric Francois, MD, PhD, Potentia’s president and CEO. Potentia notes that 4 studies have demonstrated a genetic link between the complement system and AMD, providing evidence that complement activation plays a significant role in the cause of the disease. POT-4 will be the first complement inhibitor tested in patients with AMD. “These recent data have sparked hope that AMD can be treated with complement inhibitors, which help treat the early stages of the disease. We are hopeful that POT-4 may represent a new therapeutic option for patients with dry and wet forms of the disease,” says Dr. Francois. Potentia Pharmaceuticals, based in Louisville, Ky, is focused on developing new approaches to the treatment of complement-related inflammatory diseases.