In my original article focusing on the truths and obfuscations of Ocata's (NASDAQ:OCAT) phase 1 clinical trials, I explored what has been seen so far with the embryonic stem cell (ESC) derived retinal pigmented epithelium (RPE) transplant for age-related macular degeneration and Stargardt's macular dystrophy. At the time of publication, investors were still unsure of the trial design, with the company providing relatively vague details on numbers and endpoints.
Today, Ocata submitted the trial protocol for PORTRAY, a phase 2 study of subretinally injected RPE cells in patients with advanced, non-exudative (dry) AMD. This represents a momentous shift in the company's operations, and I would like to provide those interested in Ocata Therapeutics with a little more color regarding how this trial is designed and why its endpoints are important.
Number Of Patients And Study Design
Ocata will enroll a total of 60 patients into 3 cohorts. Each cohort will have 20 patients (15 treated, 5 sham control) undergoing different immunosuppression regimens following the procedure. Patients must have best corrected visual acuity (BCVA) of between 20/800 and 20/80.
Treated patients will all be given the same immunosuppressive regimen, but the time of treatment will vary. In cohort 1, patients will receive 12 weeks of post-op immunosuppression. Cohort 2 patients will continue immunosuppression for 6 weeks. Cohort 3 won't receive continued immunosuppression after injection. Each patient must undergo 1 week of immunosuppression prior to the therapy, which could help prevent short-term rejection promoted by the surgical procedure. The number of cells has not been specified, but it is probably safe to assume that the company will use the maximum number from phase 1, 200,000 cells, since this did not increase treatment-related adverse events.
What's so important about varying the immunosuppression regimen? AMD is a disease of advanced age (age-related being a key word there). Patients in this group are often less healthy and can't tolerate the immunosuppressive regimen as well. Given that Ocata has shown in its phase 1 data that grafts can persist for up to 4 years without continued immunosuppression, it is reasonable to surmise that immunosuppression after the most early point of treatment is an unnecessary burden to patients.
Eliminating immunosuppression could open up the number of eligible patients for future studies and post marketing.
Endpoints Of The Trial: Why Are They So Important?
For its primary endpoint, Ocata threw a curveball to the shareholders who have been paying attention to these developments. The main goal of this study is to assess the number of patients with evidence of graft failure or rejection, a feature of therapy that can be observed in as little as a few months' follow-up. Using optical coherence tomography and autofluorescence photography, Ocata can assess in real time whether there is a difference in pigmentation and growth of the graft.
This primary endpoint is beneficial both in a temporal perspective and in terms of credibility. It will be very difficult for untreated patients to experience a placebo effect when the evidence for engraftment is literally staring you in the face. Control patients who receive no cells should simply not show any signs of engraftment, so this endpoint is a low bar. Importantly, the company has mentioned its ongoing discussion with the FDA, suggesting the regulatory agency is on board with this measure of efficacy as the primary endpoint.
Of course, Ocata is not foregoing other, arguably more important measures of efficacy. The secondary endpoints include progression of geographic atrophy and change in visual acuity. These are absolutely important for making a case for efficacy of the cell therapy, especially in the context of a randomized, controlled trial.
If they are so important, why not make these endpoints the primary objectives? Advanced dry AMD is a serious condition, but many patients experience slow progression. In other clinical trials for advanced dry AMD, control patients lose a few letters over several years. Of course, some deteriorate more quickly than others, and some have stable disease for years. This variability might make it difficult to produce a strong efficacy signal using BCVA, as I discussed in my first article.
Importantly, experts in the field have written early in the phase 1 study that evidence for engraftment will be a major finding that portends disease stability and possible reversal. Before the phase 1 trial began, Raymond Lund, PhD, an eminent visual scientist at the University of Utah commented:
"The study results of ACT's RPE cells implanted in the various animal models of macular degeneration was phenomenal. If ACT observes even a fraction of that benefit in humans, it will be nothing short of a home run."
Part of the power of the animal studies was the ability to demonstrate clear evidence of engraftment. Thus, focusing on this aspect of therapy can provide a clear signal for potential partners that these cells are doing their jobs, and if the early treated vs. control data look good come Q1/Q2 2016, we'll have a much clearer picture as to whether these cells are going to help patients with these eye disease.
Ocata Therapeutics has made what looks like a small step: posting the trial design for PORTRAY. But it represents a major leap forward for the technology platform and regenerative medicine. By careful design of its trial, we should be able to answer pivotal questions in the next several months. At its corporate presentation just yesterday, Ocata CEO Paul Wotton, PhD, noted that several patients have already been enrolled into the first cohort of the study.
As always, I encourage everybody to do their own due diligence when it comes to investing in developmental-stage biotechnology stocks. However, identifying the most promising players requires remaining updated on the latest news with respect to the clinical trials that make up the life's blood of these companies. I hope I have been able to provide you with some clarity as Ocata takes a big step in our journey toward regenerative medicine.
Disclosure: I am/we are long OCAT.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.