Mounting unmet need
To illustrate the unmet need, Rabin says "there's only been one blockbuster [AMD] ophthalmology drug in the last 30 years—Genentech's
Lucentis—which is used for "wet" AMD. Lucentis doesn't correct the underlying problem, but it dries out the vascular infrastructure
of the eye, which allows patients to maintain vision rather than having blood in the eye. According to Rabin, 90 percent of
patients with AMD have dry AMD, as opposed to wet AMD; the latter, "in almost all instances, is the end stage of dry AMD."
A second reason for targeting the eye is that, like the blood/brain barrier, the eye is "immunoprivileged," meaning that transplanting
allogeneic cells into the eye will not typically trigger an immune response. The third reason for choosing the eye, says Rabin,
is that advanced scanning techniques make it possible to observe what's happening "all the way down to the cellular level"
in the back of the eye. Since ACT is dosing AMD patients with a relatively small number of cells—100,000, suspended in 150
microliters of a saline-like fluid—the therapy has the potential to become "a real off-the-shelf product," says Rabin. Currently
in Phase I, ACT's patients, after a year with no safety complications, have demonstrated remarkable results. "Our first patient
had only hand-motion vision. Now she can read three lines on an eye chart. She can thread a needle and work on a computer;
it's pretty amazing," Rabin says. Also administered by an injection, ACT's therapy is an outpatient procedure that takes about
90 seconds to perform.
In addition to AMD, ACT is also conducting trials on Stargardt's disease, which Rabin characterizes as a juvenile onset of
essentially the same problem presented in AMD, but it's a genetic defect. Preliminary results from that Phase I trial were
published in The Lancet last January. Rabin said early results were published because "this was the first time ever that a human embryonic stem cell-derived
tissue was used and demonstrated efficacy in a human trial, and also, it was the first time that any therapy demonstrated
efficacy against macular degenerative disease. Rabin adds that FDA has recognized RPE cells' unique pigmentation—there are
only two kinds of pigmented cells in the body, RPE and melanocytes in the skin—as a way to prove and validate terminal differentiation.
The cells' pigmentation makes the screening process much more effective than the standard polymerase chain reaction (PCR)
assay typically used to validate differentiation in cell therapies. "That went a long way in making the FDA comfortable that
we were not going to inject undifferentiated cells," says Rabin. The head of opthamology at FDA, Wiley Chambers, established
the three lines of an eye chart improvement as a test for visual acuity, and Rabin says he hopes to work with FDA to develop
new metrics, since early stage patients won't have lost a degree of vision equivalent to three lines on an eye chart.
Rabin, like the other executives and CEOs interviewed, is optimistic about the future of stem cell therapies. For ACT, using
hESC despite lingering perceptions among politicians and the public at large makes sense because the "efficacy, potency, and
the survivability of cells derived from embryonic stem cells versus those derived from adult stem cells is that the embryonic
stem cell-derived tissue, time after time, always outshines the adult stem cell-derived cells...it's basically the equivalent
of taking very young tissue versus very old tissue," he says.