Stem Cells in Ophthalmology Update 4 ACT Receives FDA Approval to Use hESCs to Treat Dry AMD

Advanced Cell Technology Inc., announced today that it  had received approval from the FDA to commence its clinical trial using retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs) to treat the dry form of age-related macular degeneration. ACT is now permitted to initiate a Phase I/II multicenter clinical trial to treat patients with dry AMD, the most common form of macular degeneration in the world. There are currently no approved treatments available for this prevalent disease of an aging global population. Dry AMD, representing a substantial global market opportunity and afflicts between 10-15 million Americans, and a further 10 million Europeans.

Age-Related Macular Degeneration has two predominant forms, wet and dry. Dry AMD is the most common form, accounting for almost 90% of all cases. The progress of dry AMD includes a breakdown or thinning of the layer of RPE cells in the patient's macula, the region at the center of the retina responsible for high acuity vision. Over time, the progressive loss of RPE cells and accompanying loss of photoreceptors can cause severe vision loss and even blindness.

"ACT is now the first company to receive FDA clearance for two hESC trials, and is now a true translational leader in the field of regenerative medicine," said Gary Rabin, Interim Chairman and CEO of ACT. "It marks a major step forward, not just within the stem cell sector, but, potentially for modern healthcare techniques. We plan to proceed into the clinic with both of our hESC-based programs as quickly as possible." (For both dry AMD and for treating Stargardt’s Disease, approval for which was obtained in November 2010.)

The Phase I/II trial will be a prospective, open-label study that is designed to determine the safety and tolerability of the RPE cells following sub-retinal transplantation into patients with dry AMD. Twelve patients will be enrolled in the study at multiple clinical sites. Sites currently under consideration are the Jules Stein Eye Institute at UCLA, and the Ophthalmology Department at Stanford University School of Medicine. Additional sites may be considered.

"Dry AMD is the leading cause of blindness in individuals over the age of 55," stated Robert Lanza, MD, ACT's Chief Scientific Officer. "As the population ages, the incidence of AMD is expected to double over the next 20 years, further exacerbating this unmet medical need. Using our clinical-grade hESC lines, we are able to generate a virtually unlimited and reproducible supply of healthy RPE cells. Because only a small number of cells (50-200K) are needed to treat each patient, manufacturing and distribution of the therapeutic product is scalable with many similarities to the drug businesses that pharmaceutical companies understand well. Based on our animal model studies, we are very excited about the opportunity to treat patients. In a rat model of macular degeneration, we have seen a remarkable improvement in visual performance over untreated animals, without any adverse effects. We have also maintained near-normal function in a mouse model of Stargardt's Disease, a form of juvenile macular degeneration. In addition to this trial, we plan to concurrently use our RPE cells in our Phase I/II Clinical Trial for Stargardt's Disease, which received the green light from the FDA in November. We hope to see a similar benefit in both Stargardt's Disease and Dry AMD patients."

ACT's dry AMD therapeutic program uses RPE cells derived from hESCs to replace the lost RPE cells in the patient's eyes. ACT's proprietary RPE cell manufacturing process is protected by a number of broad patents, as is the use of hESC-derived RPE cells for treating macular degeneration. While the initial portion of the clinical trial will focus on safety, in subsequent clinical trials the company hopes to demonstrate that the RPE cells injected into the retinal space will be capable of slowing or halting progression of the disease, and potentially even restoring some visual acuity to patients.

"It is estimated that over ten million Europeans suffer from Age-Related Macular Degeneration, representing a vast unmet need and a significant market opportunity," commented Edmund Mickunas, ACT's Vice President of Regulatory Affairs. "We are moving ahead aggressively to seek regulatory clearance from the European Medicines Agency to conduct clinical trials in Europe."

Iluvien Update FDA Marketing Approval Delayed

Last July, I wrote a comprehensive report about Iluvien and the status and promise of other sustained release drug delivery systems (Iluvien and the Future of Ophthalmic Drug Delivery Systems). At that time, Alimera Sciences, the company developing Iluvien (under license from pSivida) had filed a new drug application (NDA) to treat diabetic macula edema (DME). The company obtained priority review status for the NDA at the end of August, raising the expectation that an approvable letter might be obtained by the end of 2010.

However, instead of an approvable letter, Alimera Sciences received a “complete response letter” (CRL) from the FDA, communicating to the company that its NDA application “cannot be approved in its present form”.

The good news is that the FDA did not request any additional clinical trials, only that it wanted additional data and analysis from the company’s two clinical trials (the FAME study) conducted with Iluvien. The company had submitted 24 month data from the studies in its NDA and the FDA wanted an additional 12 months worth of data, out to month 36. The 36 month FAME study was completed in October, and the company is currently in the process of compiling the data requested by the FDA.

In addition, the FDA requested information concerning controls and specifications related to the manufacturing, packaging, and sterilization of Iluvien. (A hopeful sign.) The FDA also identified shortcomings in good manufacturing practices during inspections of two third-party manufacturing facilities conducted in August and September. According to the company, the third-party manufacturers are working diligently to correct the deficiencies.

Alimera has requested an expedited meeting with the FDA, expected to occur in February, and expects to be prepared to file the requested additional information by the end of the first quarter of 2011.

Based on the data we have seen for results for Iluvien through 30 months, we do not anticipate any problems with the 36 month data requested by the FDA. (See the Graph below.)

From: A presentation on the FAME Study results, by Andrew Pearson MD, Professor Ophthalmology, University of Kentucky, given at the ASRS Meeting, Vancouver, Canada, August 2010.

According to two investment reports that we have seen (from Citigroup and Oppenhiemer – both of which follow the company), the analysts believe that the company will be able to fulfill the FDA’s requests and both expect that the company will obtain marketing approval either in the 4th quarter of 2011, or 1st quarter of 2012, with product launch by early 2012.

About the FAME Study

Alimera conducted two Phase 3 pivotal clinical trials (collectively known as the FAME Study) for Iluvien involving 956 patients in sites across the United States, Canada, Europe and India to assess the efficacy and safety of Iluvien with two doses, a high and low dose, for the treatment of DME. The primary efficacy endpoint for the FAME Study was the difference in the percentage of patients whose best corrected visual acuity improved by 15 or more letters from baseline on the ETDRS eye chart at month 24 between the treatment and control groups. The study concluded in October 2010 with the final patient visit at the three-year data point.