Stem Cells in Ophthalmology Update 15 Wills Eye Joins ACT’s Clinical Trials for Dry AMD Using Embryonic Stem Cell derived RPE

Advanced Cell Technology announced yesterday that the Wills Eye Institute in Philadelphia had received institutional review board (IRB) approval to become a site for the Phase I/II clinical trial for dry age-related macular degeneration (Dry AMD) using human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells. Wills will join UCLA’s Jules Stein Eye Institute and Moorfields Eye Hospital in London as sites participating in the clinical trials for Dry AMD, under ACT’s National Clinical Trials protocols.

"The participation of Wills Eye Institute in this trial will significantly enhance our clinical program," said Robert Lanza, M.D., ACT's chief scientific officer. "Wills Eye Institute is the oldest eye-care facility in the United States and is consistently ranked as one of the best ophthalmology hospitals in the country by the U.S. News & World Report. We are looking forward to working with Dr. Regillo and his team to address the unmet medical needs of degenerative diseases of the retina. With this latest approval, the company continues to assemble a clinical team that includes the best eye hospitals and surgeons in the world in our effort to find an effective therapy for this devastating eye disease."

The Phase I/II trial for dry AMD is a prospective, open-label study designed to determine the safety and tolerability of the hESC-derived RPE cells following sub-retinal transplantation into patients with dry AMD. The trial will ultimately enroll 12 patients, with cohorts of three patients each in an ascending dosage format. Which patients will be enrolled at the Wills Eye Institute will be determined in the near future.

"Degenerative diseases of the retina often lead to a significant visual impairment," said Carl Regillo, M.D., director of clinical retina research at Wills Eye Institute and professor of ophthalmology at Thomas Jefferson University. "Replacing lost or damaged cells with functional and healthy cells may provide a treatment option that could slow vision loss, and perhaps even reverse the effects of disease. We are looking forward to collaborating with ACT to evaluate the potential of the stem cell-derived RPE cells for debilitating diseases such as Stargardt's macular dystrophy and dry AMD."

Dry AMD, or "central geographic atrophy," is the "dry" form of advanced age-related macular degeneration. Dry AMD occurs when the light-sensitive cells (photoreceptors) in the macula slowly break down, gradually blurring central vision in the affected eye. Over time, as less of the macula functions, central vision is gradually lost in the affected eye, often progressing to blindness. The loss of photoreceptors is a direct result of a preceding degeneration of the retinal pigment epithelial (RPE) layer of cells just below the retina. As many as 30 million people in the United States and Europe suffer from macular degeneration, which represents a $25-30 billion worldwide market that has yet to be effectively addressed. Approximately 10% of people ages 66 to 74 will have symptoms of macular degeneration, the vast majority suffering from the "dry" form of AMD -- which is currently untreatable. The prevalence increases to 30% in patients 75 to 85 years of age.

"We are honored to have the opportunity to work with one of the foremost eye care centers in the world", said Gary Rabin, chairman and chief executive officer of ACT. "This clinical trial represents the culmination of years of innovation and hard work by ACT's scientific team. The whole world is focused on our trials, most especially patients suffering from dry AMD and other forms of macular degeneration. Wills Eye Institute has a strong tradition of innovation and discovery, and we are excited at their participation in bringing this cutting-edge technology through the clinic."

Additional details about these studies, for which the Jules Stein Institute at the University of California, Los Angeles and Moorfields Eye Hospital in London have also received IRB approval, can be found at ClinicalTrials.gov Identifier: NCT01344993.

Editors Note: As noted in the above quote from Dr. Regillo, it can be speculated that Wills Eye will soon join both Jules Stein and Moorfields in also treating Stargardt’s disease, under ACT’s National Clinical Trials NCT01345006 and NCT01469832.

It should also be noted that Wills Eye is also one of the clinical sites participating in the Centecor (J&J) clinical study of Dry AMD using adult stem cells from umbilical cord blood, NTC01226628.

Breaking News – as of January 19th, Wills Eye had been added to ACT’s clinical protocol for treating Dry AMD with embryonic stem cell-derived RPE cells, and was actively recruiting patients.

About Wills Eye Institute

Wills Eye Institute is a global leader in ophthalmology, established in 1832 as the nation's first hospital specializing in eye care. U.S. News & World Report has consistently ranked Wills Eye as one of America's top three ophthalmology centers since the survey began in 1990. Wills Eye is a premier training site for all levels of medical education. Its resident and post-graduate training programs are among the most competitive in the country. One of the core strengths of Wills is the close connection between innovative research and advanced patient care. Wills provides the full range of primary and subspecialty eye care for improving and preserving sight, including cataract, cornea, retina, emergency care, glaucoma, neuro-ophthalmology, ocular oncology, oculoplastics, pathology, pediatric ophthalmology and ocular genetics, refractive surgery and retina. Ocular Services include the Wills Laser Correction Center, Low Vision Service, and Diagnostic Center. Its 24/7 Emergency Service is the only one of its kind in the region. Wills Eye also has a network of nine multi-specialty, ambulatory surgery centers throughout the tri-state area. To learn more, please visit www.willseye.org .

Stem Cells in Ophthalmology Update 21 Clinical Trial Details

As with my inquiry into clinical trials underway using gene therapy in ophthalmology, Table 3 Gene Therapy in Ophthalmology - Ongoing Clinical Trial Details, I have undertaken a similar survey of the number of patients currently treated using stem cells. I found nine ongoing clinical trials and one about to begin.

As in the previous study, I visited the clinical trial information sites and extracted the pertinent information for use in this table, Table 3. Stem Cell Therapy in Ophthalmology - Ongoing Clinical Trial Details.

I then contacted each of the principals or sponsor involved in the study and requested the number of patients treated to date. The response to date has not been as good as with the gene therapy trials, but here is what I was able to find out.

Only two companies/institutions involved answered my request, and so I can only reliably report that 17 patients have been given stem cells for treatment of ophthalmic disorders to date.

I hope to gather additional information from either the clinical investigators or others and will update this table as new information is obtained.

Here, then, is the initial version of this table.

A downloadable pdf file of the above table is available by request.

To obtain copies of the current versions of the first two tables, listed below, please send me an email.

Table 1. Stem Cell Companies/Institutions Active in Ophthalmology

Table 2. Stem Cell Therapy in Ophthalmology by Application

ELLEX 2RT Retinal Regeneration Laser An Update – First Clinical Results

In November 2007, just prior to that year’s AAO meeting, I learned about a new laser that had the potential to alleviate the early stages of age-related macular degeneration and other retinal diseases including diabetic maculopathy, caused by compromised Bruch’s membrane. The laser-based therapy was called ELLEX’s 2RT (Retinal Regeneration Therapy).

The theory behind the therapy was based on research conducted by Professor John Marshall at St. Thomas’ Hospital of London, and his colleague Dr. Ali Hussain. They found, after experimentation, that a specially-built Q-switched doubled YAG laser (532 nm) operating at 3 ns pulses, could be used subthermally to trigger a renewal process of the retinal pigment epithelial (RPE) cells, a sort of biostimulation, without damaging the overlying retina, including photoreceptors. This caused the RPE to migrate and release matrix metalloproteinases, enzymes, which act to clean up Bruchs membrane. The scientists were able to demonstrate and measure Bruch’s ability to transport water and chemicals and thus rejuvenate the retina.

      

For the rest of the story, please see my complete initial report of November 2007. (Link at the end of this post.)

First Clinical Results

In November 2008, Ellex released the six-month clinical study results of the first trial. In this clinical study, conducted at St. Thomas’ Hospital in London by Professor John Marshall, 23 patients (38 eyes) with newly-diagnosed diabetic maculopathy and/or macular edema were recruited and treated with Ellex 2RT. Seventeen patients (28 eyes) completed the six-month follow-up examination.

Patients are being followed for one year. Postoperative testing includes optical coherence tomography and microperimetry.

At the six-month follow-up, for the17 patients (28 eyes), the LogMar visual acuity had improved by two or more lines in 43% of eyes and between one and two lines in 28%. It remained unchanged in 15% of eyes, and deteriorated by two or more lines in 14%. Central macular thickness decreased by more than 5% from baseline in 46% of patients, remained stable in 39%, and had an increase of more than 5% in 15% of patients. The number of hard exudates decreased in 41% of eyes, stayed stable in 43%, and increased in 16%. Vascular leakage decreased in 55% of eyes, was unchanged in 31%, and increased in 14%. Slit-lamp ophthalmoscope microperimetry confirmed that photoreceptor function was not affected by the laser treatment. No adverse effects occurred during the study period.

The six-month results show that Ellex 2RT is clinically safe and effective in the treatment of macular edema secondary to diabetic retinopathy.

An example of the minimal damage to retinal cells is shown in the following illustration of 2RT treated Porcine RPE:

Research Program Update (April 2010)

Since the release of preliminary clinical results in 2007 and of the six-month results in 2008, Ellex has initiated a series of pilot clinical studies aimed at evaluating the clinical efficacy of Ellex 2RT for a number of indications, the most important of which is age-related macular degeneration (AMD). The studies are making good progress, with eight prototype systems currently in use throughout Australia and the United Kingdom in these studies. Patient recruitment is nearing completion in two of the key pilot studies, with follow-up planned over a 12-month period.

Studies focused on diabetic macula edema (DME) and proliferative diabetic retinopathy (PDR) are being undertaken in collaboration with the Royal Adelaide Hospital at three study sites. A major benefit of these studies is that they include control groups, allowing Ellex to more accurately benchmark the effect of Ellex 2RT treatment against conventional laser treatment.

A third study, focused on early AMD treatment, is being undertaken in collaboration with the Royal Victorian Eye and Ear Hospital, a major Australian teaching institution, under Professor R. Guymer.

Ellex will present preliminary results from these studies at the 2010 ARVO meeting in May. Once the results from this round of pilot studies have been fully analyzed, the company will evaluate the opportunity to undertake a multi-center randomized study, and look to expand their study sites beyond Australia and the UK.

In addition, as announced earlier this month, Ellex has sublicensed the SRT (selective retinal therapy) patent, U.S. 5,549, 596, from Massachusetts General Hospital, and can now enter the U.S. market with this technology.

(For more information on this development, please see my report: AMD Update 8: Breaking News – Ellex Sublicenses SRT Patent, linked at the end of this report.)

References:

Press Release: Ellex Announces Six-Month Results on Retina Regeneration Therapy, November 2008

Can Early Laser Therapy Delay Disease Progression?, John Marshall, Retinal Physician, September, 2009.

Links:

Ellex 2RT Retina Regeneration Therapy: A First Report (November 2007)

AMD Update 8: Breaking News -- Ellex Medical Sublicenses SRT Patent

(April 2010)