Encouraging New Paper on ACT Stem Cell-Based Trial for Macular Degeneration

The stem cell biotech Advanced Cell Technology (ACT) reported new, positive data in a paper in Lancet from their clinical trials using retinal pigmented epithelial cells (RPEs) made from human embryonic stem cells (hESC) for treatment of different forms of macular degeneration (MD).

The paper was entitled “Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies” with first author Steven D. Schwartz and senior author Robert Lanza, CSO of ACT.

These two trials (one each for Stargardt’s MD and age-related MD (AMD) with 9 treated patients each) are combined prospective phase 1/2 studies. The primary goal of these trials is to assess drug safety. Importantly so far no major adverse outcomes were reported, but some adverse side effects appeared related to the procedure itself and to immunosuppression so those must be kept in mind. As to the latter, in theory an autologous induced pluripotent stem cell (IPSC)-based therapy could be superior in terms of likely not needing immunosupression, but there may be practical advantages to an hESC-based therapy in other ways (e.g. lower cost).

A potential major bonus here in the ACT report today is that despite the fact that the trial used relatively low doses of cells and despite the primary measure here being safety, ACT reported in this publication that a substantial number of the patients also had measurable improvements in their vision:

Vision-related quality-of-life measures increased for general and peripheral vision, and near and distance activities, improving by 16–25 points 3–12 months after transplantation in patients with atrophic age-related macular degeneration and 8–20 points in patients with Stargardt’s macular dystrophy.

This is a very positive, even if somewhat surprising development in terms of potential efficacy. The main cause of vision impairment in MD is not thought to be loss of RPEs, but rather photoreceptor cells. So how could transplanted RPEs (and relatively low cellular doses for the most part at that) potentially improve vision? The working theory seems to be that the RPEs might help remaining photoreceptors stay alive, healthier, and perhaps more properly functional.

ACT FIgure 1

I thought it was notable that 72% of the transplant recipients had measurable increases in subretinal pigmentation and pigmentation gradually increased over time, indicative of a high-rate of stable engraftment of the RPEs (see image above from Figure 1).

The authors summarized their interpretation of their results in this way:

Our study provides the first evidence of the medium-term to long-term safety, survival, and possible biological activity of pluripotent stem cell progeny after transplantation in people with any disease. The results suggest that human-embryonic-stem-cell-derived cells could provide a potentially safe new source of cells for the treatment of various medical disorders that require tissue repair or replacement.

I’ll be very curious to see the future results as ACT likely begins to treat patients with higher doses of cells and patients with relatively earlier (potential more treatable) stages of MD.

In the wider scheme of things, ACT’s results are also encouraging for other stem cell biotechs and other similar kinds of studies. For example, it will be interesting to see how the IPSC-based RPE clinical study in Japan for MD proceeds and how the BioTime subsidiaries (1) Asterias’ hESC-based trial for spinal cord injury and (2) Cell Cure’s hESC-based trial for AMD proceed. There can perhaps be greater hope of safety for these other vision-related pluripotent stem cell-based trials as well now and also for other studies such as ViaCyte’s hESC-based trial for Diabetes, which may start very soon.

Still, it’s relatively early days and these kinds of endeavors are risky marathons rather than sprints, so quite a lot of caution is in order.

Disclosure. The author has a small, long-term stock position in ACT. This post is not intended to be financial or health advice. Consult your financial advisor and doctor (not blogs) for making those kinds of important decisions.

BioTime’s Cell Cure Files IND with FDA for ES cell AMD therapy

Cell Cure LogoStem cell biotech BioTime announced the news today that its subsidiary Cell Cure Neurosciences (Cell Cure) has filed an IND with the FDA for an embryonic stem (ES) cell-based therapy for Dry age-related macular degeneration (AMD). The product to be tested is OpRegen, which the company indicates is “the first IND for an ES cell-based therapy developed in Israel.”

Cell Cure in its PR on this IND also listed three other key bullet points:

  • “IND filed for Phase I/IIa dose escalation trial in patients with dry-AMD
  • No approved therapy exists for dry-AMD, the leading cause of visual impairment in the aging population
  • OpRegen® will be the first preparation of xeno-free RPE cells to be evaluated clinically for dry-AMD”

I’m very curious to see how OpRegen performs in the trial.

This is only the third IND for an ES cell-based therapy with the other two coming from Advanced Cell Technology (ACT) and Geron.

I asked Dr. Mike West, CEO of BioTime, about the trial and he had this to say:

“Age-related degenerative diseases are really the frontier of medicine in our time. The aging of 76 million baby boomers and the consequent tsunami of healthcare costs associated with palliative as opposed to truly therapeutic care is a top national priority. I believe that AMD is only one of numerous examples where the stable engraftment of young healthy cells may provide important new therapeutics for these long-term and expensive problems of aging.”

Macular degeneration of various kinds is a focus of a number of pluripotent stem cell trials. For example, the first ever iPS cell-based clinical study, led by Masayo Takahashi, is also focusing on AMD.

Disclosure. I have no financial interests in BioTime or Cell Cure and have a small long position in ACT. This post is not financial advice.

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