Identifying the visually impaired patients most likely to benefit from jCyte’s stem cell therapy

We have written about jCyte many times on The Stem Cellar. For one reason, they are showing really encouraging results in their treatment for retinitis pigmentosa (RP). And now they have taken an even deeper dive into those results and identified which patients may be most likely to benefit from the therapy.

RP is a rare genetic disorder that slowly destroys the rods and cones, the light sensing cells in the back of the eye. If you look at the image below the one on the left shows normal vision, the one on the right shows what happens with RP. At first you start to lose night vision, then other parts of your vision are slowly eroded until you are legally blind.

RP starts early, often people are diagnosed in their teens and are legally blind by middle age. There is no treatment, no cure. It’s estimated that as many as 100,000 people in the US have RP, as many as two million worldwide.

That’s where jCyte comes in. They developed jCell, a therapy using adult stem cells that have been changed into human retinal progenitor cells (hRPCs). These are injected into the back of the eye where they secrete small proteins called neurotrophic factors.

Dr. Henry Klassen, one of the founders of jCyte, says jCell works by preserving the remaining photoreceptors in the eye, and helping them bounce back.

“Typically, people think about the disease as a narrowing of this peripheral vision in a very nice granular way, but that’s actually not what happens. What happens in the disease is that patients lose like islands of vision. So, what we’re doing in our tests is actually measuring […] islands that the patients have at baseline, and then what we’re seeing after treatment is that the islands are expanding. It’s similar to the way that one would track, let’s say a tumor, in oncology of course we’re looking for the opposite effect. We’re looking for the islands of vision to expand.”

And in patients treated with jCell those islands of vision did expand. The team followed patients for one-year post treatment and found that patients given the highest dose, six million cells, experienced the biggest improvement and were able to read, on average, 16 more letters on a standard eye chart than they had been before treatment. In comparison people given a sham or placebo treatment only had an improvement of less than two letters.

This group also experienced improvements in their peripheral vision, their ability to distinguish objects in the foreground from the background and were better able to get around in low light.

But that’s not all. Dr. Sunil Srivastava, with the Cleveland Clinic Cole Eye Institute, did a detailed analysis of patients treated in the trial and identified central foveal thickness (CFT- the part of the eye located in the center of the retina) as an important marker for who would be most likely to benefit from jCell. People who started out with a higher CFT score were most likely to get the biggest benefits.

In a news release, jCyte CEO Dr. Shannon Blalock said the findings are really encouraging: “We look forward to working closely with our scientific advisory board and principal investigators to apply these key learnings to our upcoming pivotal study of jCell to optimize its probability of success in an effort to advance the clinical development program of our RMAT designated therapy for RP patients who currently have no treatment options.”

Encouraging news for treatment targeting retinitis pigmentosa

While most people probably wouldn’t put 2020 in their list of favorite years, it’s certainly turning out to be a good one for jCyte. Earlier this year jCyte entered into a partnership with global ophthalmology company Santen Pharmaceuticals worth up to $252 million. Then earlier this week they announced some encouraging results from their Phase 2b clinical trial.

Let’s back up a bit and explain what jCyte does and why it’s so important. They have developed a therapy for retinitis pigmentosa (RP), a rare vision destroying disease that attacks the light sensitive cells at the back of the eye. People are often diagnosed when they are in their teens and most are legally blind by middle age. CIRM has supported this therapy from its early stages into clinical trials.

This latest clinical trial is one of the largest of its kind anywhere in the world. They enrolled 84 patients (although only 74 were included in the final analysis). The patients had vision measuring between 20/80 and 20/800. They were split into three groups: one group was given a sham or placebo treatment; one was given three million human retinal progenitor cells (hRPCs), the kind attacked by the disease; and one was given six million hRPCs.

jCyte CEO Paul Bresge

In an article in Endpoints News, jCyte’s CEO Paul Bresge said there was a very specific reason for this approach. “We did enroll a very wide patient population into our Phase IIb, including patients that had vision anywhere from 20/80 to 20/800, just to learn which patients would potentially be the best responders.”

The results showed that the treatment group experienced improved functional vision and greater clarity of vision compared to the sham or placebo group. Everyone had their vision measured at the start and again 12 months later. For the placebo group the mean change in their ability to read an eye chart (with glasses on) was an improvement of 2.81 letters; for the group that got three million hRPCs it was 2.96 letters, and for the group that got six million hRPCs it was 7.43 letters.

When they looked at a very specific subgroup of patients the improvement was even more dramatic, with the six million cell group experiencing an improvement of 16.27 letters.

Dr. Henry Klassen

Dr. Henry Klassen, one of the founders of jCyte, says the therapy works by preserving the remaining photoreceptors in the eye, and helping them bounce back.

“Typically, people think about the disease as a narrowing of this peripheral vision in a very nice granular way, but that’s actually not what happens. What happens in the disease is that patients lose like islands of vision. So, what we’re doing in our tests is actually measuring […] islands that the patients have at baseline, and then what we’re seeing after treatment is that the islands are expanding. It’s similar to the way that one would track, let’s say a tumor, in oncology of course we’re looking for the opposite effect. We’re looking for the islands of vision to expand.”

One patient did experience some serious side effects in the trial but they responded well to treatment.

The team now plan on carrying out a Phase 3 clinical trial starting next year. They hope that will provide enough evidence showing the treatment is both safe and effective to enable them to get approval from the US Food and Drug Administration to make it available to all who need it.