Thursday, January 26, 2012

AMD Update 16: Visualization of Drusen and RPE With New Software Application for Zeiss HD-OCT: A New Aid for Assessing Both Dry and Wet AMD

As noted below, by both Drs. Rosenfeld and Puliafito, this new diagnostic tool will play an important role in assessing and speeding the development of new treatments for both dry and wet AMD that are being researched and brought to the market.

In an announcement on January 20th, Carl Zeiss Meditec said that it had added new dry age-related macular degeneration (Dry AMD) and new glaucoma diagnostic tools for its Cirrus HD-OCT (High Definition Optical Coherence Tomography), and the new software, version 6.0, had received clearance from the US Food and Drug Administration (FDA).

Zeiss Meditec Cirrus HD-OCT
"Designed to help ophthalmologists manage the growing number of patients with serious eye diseases, the new Cirrus application package offers a more comprehensive approach to disease management, delivering more thorough and more meaningful clinical analysis within the retina and glaucoma workplaces", said Dr. Ludwin Monz, President and CEO of Carl Zeiss Meditec AG.

The new Cirrus HD-OCT retina application provides Advanced Retinal Pigment Epithelium (RPE) Analysis, which enables clinicians to objectively monitor changes associated with dry AMD. The application tracks change in RPE elevation area and volume often associated with drusen. It also identifies and measures the area of transparent regions in the RPE that can develop with geographic atrophy. Unlike blue light fundus autofluorescence (FAF), Cirrus measurements are not affected by macular pigment in the fovea and provide an objective assessment of geographic atrophy status as part of a standard OCT exam.

Further expanding Carl Zeiss Meditec's retina workplace, the Cirrus HD-OCT application package also includes Enhanced Depth Imaging (EDI), which allows for better visualization of deeper tissues, such as the choroid, enabling doctors to better understand the role of this anatomy in retinal disease.

A Look at the Retinal Layers Able to be Visualized

"The new integrated RPE Analysis software now offers clinicians the opportunity to objectively analyze all stages of AMD, especially the progression of dry AMD. Now one imaging technique, the Cirrus HD-OCT, can quantitate drusen and geographic atrophy, as well as choroidal neovascularization (CNV) and any elevation of the RPE associated with wet AMD," said Dr. Philip J. Rosenfeld, Professor of Ophthalmology at the Bascom Palmer Eye Institute and collaborator with Carl Zeiss Meditec in developing the techniques underlying the new applications. "Now we don't have to move patients between different instruments to visualize drusen, geographic atrophy, and CNV. These analyses will help clinicians stage and monitor disease progression today and will be critical to managing response to therapy as new treatments come to market."

As pointed out by Carmen Puliafito, MD, speaking at Retina 2012, held last week in Hawaii, “New algorithms to translate spectral domain optical coherence tomography images have begun to allow retinal specialists to measure drusen volume and area for the first time and may offer a better understanding of age-related macular degeneration. We now have some really objective tools that we can use to look at disease progression and then perhaps come to a better understanding of the pathophysiology of what exactly this disease is."

Fundus photography allows ophthalmologists to see drusen, but trying to count or measure it is nearly impossible, Dr. Puliafito said. These new methods will allow ophthalmologists to view the internal limiting membrane and the retinal pigment epithelium and where the retinal pigment epithelium should be, resulting in elevations that correspond to drusen, he said. This provides a major step forward in quantification.

"Drusen come, drusen go. And in their wake can be geographic atrophy, choroidal neovascularization or absolutely nothing," Dr. Puliafito said. "We now have some really objective tools to look at disease progression" to better understand AMD.

The new Cirrus HD-OCT application package also extends Carl Zeiss Meditec`s comprehensive suite of glaucoma diagnostic tools, adding new Ganglion Cell Analysis and Optic Nerve Head Progression Analysis. The Ganglion Cell Analysis evaluates the thickness of the combined ganglion cell and inner plexiform layers and compares the results to normative data. The new software package also expands Guided Progression Analysis (GPA) to automatically track progression of average cup-to-disc ratio and other optic nerve head parameters.

With these new clinical applications, Cirrus HD-OCT now spans the full spectrum of visualization and structural assessment in glaucoma: angle assessment, central corneal thickness measurement and analyses of retinal nerve fiber layer, ganglion cell layer and optic nerve head.

The new software package addresses a global market by adding user interfaces in Japanese, Chinese, Korean, German, French, Italian and Spanish to the original English interface. The software received its CE mark for distribution to major European markets in November, 2011.

Monday, January 23, 2012

Stem Cells in Ophthalmology Update 16: Results of First Embryonic Stem Cells in Treatment of Eye Disease Reported in Peer-Reviewed Journal

Two significant events were reported today by Advanced Cell Technology. First, the company said that a peer-reviewed publication of clinical results from its first patients treated at UCLA Jules Stein Eye Institute had been placed online by the UK’s The Lancet. The study reported on the four-month results of a safety study initiated in human patients last July. In that study, one eye of a patient with Stargardt’s macular dystrophy (SMD), and another with the dry form of AMD were given doses of human embryonic stem cell-derived retinal pigment epithelial (RPE) cells.

The second event was the announcement that the first patient had been treated with stem cells in the UK arm of the Stargardt’s study, at Moorfields Eye Hospital last Friday. (See Update 10 for more information.)

As reported in The Lancet article, Embryonic Stem Cell Trials for Macular Degeneration: A Preliminary Report, in addition to showing no adverse safety issues, structural evidence confirmed that the hESC-derived cells survived and continued to persist during the study period reported. Both patients had measurable improvements in their vision that persisted for more than four months.

As noted by the lead author (Dr. Steven Schwartz), in his findings: “Controlled hESC differentiation resulted in greater than 99% pure RPE. The cells displayed typical RPE behavior and integrated into the host RPE layer forming mature quiescent monolayers after transplantation in animals. The stage of differentiation substantially affected attachment and survival of the cells in vitro after clinical formulation. Lightly pigmented cells attached and spread in a substantially greater proportion (>90%) than more darkly pigmented cells after culture. After surgery, structural evidence confirmed cells had attached and continued to persist during our study. We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months. Although there is little agreement between investigators on visual endpoints in patients with low vision, it is encouraging that during the observation period neither patient lost vision. Best corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual acuity chart) in the study eye of the patient with Stargardt’s macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular degeneration (from 21 ETDRS letters to 28).”

At four months following treatment, no hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection were observed in either patient at any time. Detailed clinical and diagnostic laboratory assessments were performed at multiple post-transplantation evaluations. Abnormal growth (or tumor formation) would be considered a significant safety concern for stem-cell based therapies, in particular those derived from hESCs due to their pluripotency; it is therefore critical to control the differentiation of hESCs. Results reported indicate that stem cell differentiation was well controlled in these patients. No adverse safety signals were detected.

Anatomic evidence of successful stem cell derived RPE transplantation was observed clinically and with high resolution imaging technology in the patient with SMD. This evidence included increasing pigmentation at the level of RPE, within the area of the transplant, beginning one week after transplantation and throughout the follow-up period. Transplanted stem cell derived RPE appeared to engraft in the proper location and assume normal RPE morphology. Engraftment and increasing pigmentation were not detected in the dry AMD patient. However, both patients showed some visual improvement at the four month follow-up period. (Emphasis added by editor.)

Measuring visual improvement in patients with very low vision is difficult, and no regulatory consensus exists regarding on how best to measure visual changes in these patients. As reported in The Lancet, the visual acuity of the Stargardt's patient improved from hand motions only to 20/800 vision. Before treatment, the patient was unable to read any letter on the ETDRS visual acuity chart. However, by two weeks post-transplantation, she was able to start reading letters, which improved to five letters at one to three months in the treated eye.

"It has been over a decade since the discovery of human embryonic stem cells," said Robert Lanza, M.D., chief scientific officer of ACT, and co-senior author of the paper. "This is the first report of hESC-derived cells transplanted into patients, and the safety and engraftment data to date look very encouraging. Although several new drugs are available for the treatment of the wet type of AMD, no proven treatments currently exist for either dry AMD or Stargardt's disease. Despite the progressive nature of these conditions, the vision of both patients appears to have improved after transplantation of the cells, even at the lowest dosage. This is particularly important, since the ultimate goal of this therapy will be to treat patients earlier in the course of the disease where more significant results might potentially be expected. We would like to thank the patients for their willingness to participate in these safety studies. It has provided the scientific community with important data and experience that will help advance efforts in the regenerative medicine field."

Human embryonic stem cells can provide a superior source of replacement tissue by producing an unlimited number of healthy "young" cells with potentially reduced immunogenicity. The eye is an immune privileged site due to the protection of the subretinal space by a blood-ocular barrier, and as a result only low and transient doses of immunosuppression were used. No signs of rejection or inflammation were observed in either patient, and doctors will continue to monitor both patients.

"We are extremely pleased with these first clinical results from our ongoing studies to determine the safety and tolerability of subretinal transplantation of hESC-derived RPE cells," said Gary Rabin, chairman and CEO of ACT. "This represents an important milestone not only for ACT and UCLA"s Jules Stein Eye Institute but also for the field of regenerative medicine. The publication of these data in The Lancet demonstrates their quality and importance. We would like to thank the team, patients and principal investigator for their contributions to this study which have resulted in this outstanding publication. The data underscore the potential of stem cell therapies and regenerative medicine to realize the possibility repairing or replacing tissues damaged from disease. We are looking forward to the continuation of our clinical programs and the generation of additional data."

The hESC-derived RPE cells underwent extensive safety studies prior to transplantation. The cells were confirmed to be free of animal and human pathogens, and a high sensitivity assay was performed to rule out the presence of any undifferentiated hESCs in the final product, a risk factor for tumor formation. Controlled hESC differentiation resulted in near-100 percent pure RPE. A central feature of hESCs is that the stage of in vitro differentiation can be controlled to maximize survival and functionality. The data here show that the extent of RPE maturity and pigmentation may dramatically impact subsequent attachment and growth of the cells after transplantation.

"It is an honor to initiate the translational research process as we begin to take stem cell biology out of the laboratory and into the operating room," said Steven Schwartz, M.D., Ahmanson Professor of Ophthalmology at the David Geffen School of Medicine at UCLA and retina division chief at UCLA's Jules Stein Eye Institute, principal investigator of the study and author of the publication. "The scientific and regulatory teams, as well as the leadership at ACT have been exemplary. Recognizing that we are reporting positive preliminary safety data, and a functional signal that there may be a biological benefit to patients in terms of visual increase, makes this is an exciting time for ophthalmology and regenerative medicine."

Both trials are prospective, open-label studies designed to determine the safety and tolerability of hESC-derived RPE cells following sub-retinal transplantation into patients with SMD and dry AMD at 12 months, the studies' primary endpoint. Each trial will enroll 12 patients each, with cohorts of three patients each in an ascending dosage format. Both the SMD and dry AMD patient had subretinal transplantation of the smallest dose (50,000 cells) of fully-differentiated RPE cells derived from hESCs.

The paper's other authors are Jean-Pierre Hubschman, Gad Heilwell, Valentina Franco-Cardenas, Carolyn K. Pan, and Rosaleen M Ostrick at UCLA and the Jules Stein Institute; and Edmund Mickunas, Roger Gay, and Irina Klimanskaya at ACT.

Editor’s Note: It should be noted that the smallest dosage allowed was used in these first patients in a safety study, in severely affected patients. Although some vision improvement was noted, it should be expected that higher doses, and in less-affected patients, might provide even better outcomes. Time will tell.

Wednesday, January 18, 2012

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 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 .

Saturday, January 14, 2012

Gene Therapy in Ophthalmology Update 8: Promising Results in the Treatment of Leber’s Congenital Amaurosis (LCA)

As noted in the Gene Therapy in Ophthalmology by Application table shown in Update 7, there are seven clinical trials underway at various institutions aimed at the treatment of Leber’s Disease. Some of these trials have been underway for several years with multiple patients having been treated.

When I sent a copy of the table to Dr. Stephen Rose, chief research officer for the Foundation Fighting Blindness for comments and review, I also asked the question, “Who is tracking and reporting on the results of the patients already treated?” I didn’t get a direct response, but a few days later, the FFB reported the following story on its web site, providing some insight into the results being obtained.

Foundation Fighting Blindness

January 13, 2012 - Three years after it began, the landmark Phase I gene therapy clinical trial for people with Leber congenital amaurosis (LCA) at the Universities of Pennsylvania and Florida (NCT00481546) continues to go very well. Overall safety and vision improvements have been sustained. All 15 participants in the study, ranging in age from 11 to 30, have demonstrated vision improvement to varying degrees, including increases in visual field, night vision and mobility. Improvements in visual acuity only occurred in those who entered the trial with the lowest visual acuity.

"We are extremely pleased with the latest report coming from the Penn-Florida study. It is imperative that we demonstrate long-term safety and effectiveness of the treatment, and the team is doing that superbly," says Dr. Stephen Rose, chief research officer, Foundation Fighting Blindness. "We are also impressed by the depth and scope of their analyses of the treatment, which not only validate their results, but will greatly increase the chances of success for future gene therapy clinical trials for LCA and other retinal diseases."

The University of Pennsylvania's Dr. Samuel Jacobson, lead investigator for the clinical trial, and Dr. Artur Cideciyan, his co-investigator, say their team has learned that targeting certain areas of the retina for injection of the treatment is critical to both safety and effectiveness. Specifically, injections underneath the fovea, the central area of the retina with the highest concentration of cones, didn't improve vision and could potentially lead to damage or detachment. They believe that a strategy of two or three injections at different points outside the fovea will be optimal for treating many of these LCA patients.

Dr. William Hauswirth, a Foundation-funded gene therapy development expert and trial co-investigator from the University of Florida, is conducting lab studies of a gene therapy injection approach that may reduce the overall risk of retinal damage and detachment. As a potentially safer alternative to subretinal injections, he is evaluating intravitreal injections made near the front of the retina. The challenge with the intravitreal approach is ensuring that the treatment, which is contained in a tiny drop of liquid, gets to the retinal cells that need it. Dr. Hauswirth notes that different injection sites and strategies might be warranted for different diseases.

In addition to the Universities of Pennsylvania and Florida study, four other clinical trials are underway for gene therapy for LCA caused by mutations in the RPE65 gene. Those studies are being conducted by: The Children's Hospital of Philadelphia (CHOP), Moorfields Eye Hospital in London, Hadassah Medical Organization in Jerusalem, and Oregon Health & Science University, for the company AGTC. The Foundation is funding the clinical trials at CHOP and Moorfields, and funded much of the preclinical work that made them all possible.

All of the gene therapies in these clinical trials use a manmade adeno-associated virus, or AAV, to deliver normal copies of the RPE65 gene to replace the mutated copies in the retina. More than 40 people have been treated in the five RPE65 gene therapy clinical trials.

For additional information about this study, also see Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations, published in the Archives of Ophthalmology, September 12, 2011.

Gene Therapy in Ophthalmology Update 7: 2012 the Year for Gene Therapy?

While I have previously written about the progress being made in the use of stem cells in ophthalmology (see Stem Cell Update 13) and described the 9-10 clinical trials currently underway or about to start (see Stem Cell Update 14), recent events point to 2012 becoming a breakthrough year for the use of gene therapy to overcome genetic defects that cause several ophthalmic diseases.

In the accompanying table, I list the fourteen clinical trials that I know about in the use of gene therapy in treating ophthalmic disease. Half of the trials are aimed at treating Leber’s Congenital Amaurosis (LCA), while three are for treating the wet form of AMD; one is underway for treating Choroideremia; one for Stargardt’s Disease; and two are aimed at different forms of retinitis pigmentosa (Autosomal Recessive RP and Usher Syndrome 1b).

In addition, I show at least twenty four clinical trials in either the pre-clinical (animal study) mode, or a couple in the IND-preparation mode. That is close to forty clinical trials using gene therapy to treat ophthalmic diseases.

The treatment of Leber’s using gene therapy has been ongoing for at least three years and, as I will show in the next update (Gene Therapy Update 8), those trials are going quite well, with many of the patients showing improved vision.

Finally, as another indicator that gene therapy will play an important role in ophthalmology in this year, Ocular Surgery News is about to begin a special section, OSN Retina, to be part of it’s coverage of the ophthalmic scene. The January 25 issue of Ocular Surgery News will include OSN Retina - a leading destination that will provide retina specialists with more relevant information specific to their field.. The premiere issue will include a feature on how  “Retinal gene therapy may pave the way for attempts to reverse genetic disease: Advancements in retinal gene therapy have prompted a collaborative effort to attain FDA approval.”

For those of you who wish a better understanding of how gene therapy works, and until I write the Primer on the Use of Gene Therapy in Ophthalmology, which I have threatened to write for the past year and a half, you can gain an understanding by reading my first article about gene therapy, written back in November 2010, The Use of Gene Therapy in Treating Retinitis Pigmentosa and Dry AMD by Retrosense.

Here then is my latest version of Gene Therapy in Ophthalmology by Application:

A pdf file of the table is available by email request.

Wednesday, January 11, 2012

Stem Cells in Ophthalmology Update 14: Current Stem Cell Clinical Trials

Thanks to new friend, Alexey Bersenev, and his stem cell blog, Hematopoiesis, I have been able to add several companies and medical institutions to my list of those involved in ophthalmic clinical trials using stem cells. Alexey recently posted a blog entry, Cell therapy clinical trials in 2011, describing his efforts to put together a list of entities undertaking stem cell clinical trials. He came up with a total of 151 clinical trials underway, of which eight were in ophthalmology.

I am able to add one that he missed, giving a total of nine clinical trials underway (and another about to start). The new list, showing the trials by ophthalmic application, are presented in the accompanying table.

Anyone wishing a pdf file of the table can get it by sending me an email request.

Tuesday, January 10, 2012

Stem Cells in Ophthalmology Update 13: Advanced Cell Technology Update

In the wake of the 60 Minutes expose of illegitimate stem cell activities, I thought I would bring you good news about a couple of  legitimate, government approved clinical trials using stem cells.

As part of the Biotech Showcase 2012 conference program, being held in San Francisco, ACT company chairman and CEO, Gary Rabin will present talks on his company’s progress as part of two panels at the Regenerative Medicine State of the Industry Briefing. In advance of his two talks, the company released a statement about the ongoing clinical trials, results and timing, on his From the Chairman company blog.

In his statement, reproduced below, Rabin commented on the progress of two of the three government approved clinical trials currently underway at UCLA’s Jules Stein Eye Institute on treating Stargardt’s Macular Dystrophy and the dry form of age-related macular degeneration (Dry AMD). (See Update 8 and Update 9 for additional information.) (The other clinical trial, also for treating Stargardt’s, is taking place in the UK at Moorfields Eye Hospital in London.[Update 10])

As I reported last July, in Update 9, the first two patients in each of the UCLA trials were treated on July 12th. Since these are safety studies, the investigators are carefully watching the first patients response to the treatment before treating other patients in the twelve patient trials.

Rabin stated, “As you are no doubt aware, the trials at UCLA are being conducted by Dr. Steven Schwartz of JSEI and overseen by our chief scientific officer, Dr. Robert Lanza. Each patient has received an injection of 50,000 hESC-derived RPE cells in one eye. Both trials will involve twelve patients, and are designed to evaluate the safety and tolerability of the injected RPE cells. Based on the results of the first patient in each study, we are authorized by the Data and Safety Monitoring Board (DSMB) to move forward with the next two patients in the studies, each of whom will also be treated with 50,000 RPE cells.” (Emphasis added by editor.)

Rabin went on to say, “I am delighted to inform you that we are currently scheduled to treat our first patient in the UK at the end of next week or early the following week, and that we will be treating four additional US patients beginning that same following week.”

As for publishing the results of the studies, he said that the company would take the appropriate approach of “publishing it in the form of a paper in a prestigious, peer-reviewed medical journal. However, the peer-review process takes time. The process typically takes several months, so I am actually quite thrilled that we are now moving toward the final stages of completing it, less than six months after the first patients were treated. We are far enough along that at this point the additional waiting time will be measured only in weeks, not months.”

So, this is good news for the cell stem treatment of retinal diseases.

I have also just learned about several other clinical studies now underway in this field and will discuss them in a followup report (Update 14) to be published either later today or early tomorrow.

Now, here is the complete statement from Mr. Rabin, as taken from his company’s website:

January 10, 2012


For many of us, the New Year is a time not just for looking forward but for reflecting on events, achievements and lessons learned over the past year. I anticipate an amazing year ahead for ACT, and at the same time I also cannot help but reflect with pride on how far the company has come with its clinical programs over the past year.

IND Filing and Clinical Trials

I will never forget the moment I learned that the company's Investigational New Drug Application (IND) for its human clinical trial for Stargardt's Macular Dystrophy (SMD) had been approved by the FDA. It was clear then that ACT truly was on the road to potentially making medical history. So much has happened in the interim that it is hard to believe that happened only a bit over one year ago, in late November, 2010!

Shortly after that, our IND for Dry Age Related Macular Degeneration (Dry AMD) was also approved. The brief time since then has been a whirlwind of activity in preparation for the clinical trials, and we were enormously pleased and proud to start them in July, at the first site, UCLA's Jules Stein Eye Institute (JSEI).

As you are no doubt aware, the trials at UCLA are being conducted by Dr. Steven Schwartz of JSEI and overseen by our chief scientific officer, Dr. Robert Lanza. Each patient has received an injection of 50,000 hESC-derived RPE cells in one eye. Both trials will involve twelve patients, and are designed to evaluate the safety and tolerability of the injected RPE cells. Based on the results of the first patient in each study, we are authorized by the Data and Safety Monitoring Board (DSMB) to move forward with the next two patients in the studies, each of whom will also be treated with 50,000 RPE cells.

Part of what makes research and development in the regenerative medicine sector so exciting is that it involves sailing into largely uncharted waters. ACT's two trials are the only ongoing human embryonic stem cell-based trials, period. We are quite literally creating a new area of medicine. This means there is tremendous pressure on us to "get it right." The responsibility to provide the first-ever validation for this enormously promising new sector rests entirely on our shoulders.

I hope, then, that our many fans and followers can understand why this process takes some time. All eyes are on us, both from the standpoint of support and scrutiny. Should our trials succeed, it could provide the validation that the regenerative medicine sector has been in need of for some time. This is why, in every stage, we are bending over backwards to make sure we cross all our t's and dot all our i's. As the saying goes, Rome wasn't built in a day. If we can successfully complete these trials and bring these therapies to market, though, the potential benefits would be manifold:

*  The potential to at least partially restore sight to millions of people suffering from Dry AMD, the most common cause of blindness for people over age 55.
*  Provide a much-needed validation to the entire regenerative medicine sector.
*  Provide an enormously useful base of scientific knowledge on which we and others can develop other treatments and cures.
*  Last but not least, reward our investors for their patience and support with a return on their investment as befits a company with the only approved treatment for Dry AMD, which has a potential market size of $25-30 Billion in the US and Europe alone, as well as for SMD.

For many years, I was an equity market investment manager. That is an industry where you can evaluate results on a daily basis. Just because you can do that, though, does not mean that you should. The best investors, by far, look at long-term investment opportunities. Running a biotech company is not the same. I am well aware that we have many shareholders who want to know why we don't just treat patients and release results as fast we can, and as fast as available. To do so would be beyond foolhardy for a company like ACT. If there is anything this industry has had some issues with, it is credibility in the mainstream healthcare world. We plan to change that. But to do that, it can't happen overnight. Patient selection, clinical site selection, the timing of patient treatment, and unexpected non-ocular conditions of patients found in health screenings are among the major factors that impact patient treatment. Another factor in the timing of treating these new patients is that we will have at our disposal a new kind of three-dimensional retinal imaging technique, which has not previously been available. Believe me, the timing of patient surgeries has nothing to do with safety, efficacy or availability of suitable patients.

I know that many investors want us to go as fast as possible in treating patients. But there is a tortoise/hare effect here that I simply won't discuss now. I know that it is hard to be patient, but we are making every decision for the best interest of the company in the long run. We don't get bonus points for finishing the trial a few months earlier as compared to making it a truly game-changing medical opportunity. I know that many of you don't know me from Adam, but I'm a very methodical person. Look who we recently added to the Board - one of the leading scientists in the world; one of the best entrepreneurs in the world (founder of Life Alert and eFax), and the CFO of a highly-regarded biotech company considered to have made excellent, value-preserving large bio/pharma partnering deals. We have this under control.

One ill-conceived decision could set the company on a downward path (ACT has been there). Highly prestigious peer-reviewed medical journals do substantial review and due diligence. Top-rated eye hospitals and surgeons are very process-oriented and sometimes bureaucratic. Pushing them harder to move faster doesn't earn you any credibility or success.

Nevertheless, I am delighted to inform you that we are currently scheduled to treat our first patient in the UK at the end of next week or early the following week, and that we will be treating four additional US patients beginning that same following week.

Publishing Data

The question that inevitably comes up asks when we are going to publish the initial data from the trials. We are eagerly anticipating doing so but we are not going to just post it in raw form. This trial has the potential to make medical history and we want to share the initial results with the world in a strategic way.

The only appropriate approach with data this significant is publishing it in the form of a paper in a prestigious, peer-reviewed medical journal. However, the peer-review process takes time. The process typically takes several months, so I am actually quite thrilled that we are now moving toward the final stages of completing it, less than six months after the first patients were treated. We are far enough along that at this point the additional waiting time will be measured only in weeks, not months. We are coordinating the scientific publication with a general mainstream media release strategy (see below). When the paper is published, rest assured that we plan to leverage it to make sure it is very broadly known, not only in medicine, but in the broader medical and scientific community, as well as the investment community.

We sincerely appreciate everyone's patience as we continue this process. We are keenly aware that our investors, fans and other followers are anxious to see the data.

Thank you for your patience and thank you, as always, for your interest and support.

Gary Rabin
Chairman and CEO
Advanced Cell Technology, Inc.