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How much experience do you have with Stargardt disease?
In 2010, I was recruited to Johns Hopkins University to lead retinal dystrophies at the Wilmer Eye Institute. We conducted the largest natural history study ever undertaken on Stargardt disease, called the ProgStar study.
I felt that at Belite Bio, I could work at the forefront of drug development. Clearly, given the topline data that we’ve just released, I was right to do so. The observed treatment effect was absolutely stunning, and I’m blown away.
Keep in mind, there has never been a therapy that allows for the slowing down of neurodegeneration for any known inherited retinal dystrophies. There’s one possible exception—Luxturna, a gene therapy that was approved eight years ago—but that’s not for Stargardt disease.
Stargardt is an inherited condition, and patients develop signs of the disease very early in life. From then on, you know that you will lose vision in the coming decades and end up with legal blindness, if not worse.
There has been absolutely nothing we can do to stop it.
Intervention is simply one pill a day. We are able to slow down the progression of disease, by which I mean the loss of the cells that enable vision, by more than one-third. This still means that a patient’s vision will get worse, but at a much, much slower rate.
That’s important to understand. We’re not going to restore vision. When you think about neuronal cell degeneration in the brain, like with Alzheimer’s or Parkinson’s, that’s an impossibility.
But with five milligrams of Tinlarebant, once a day, we will be able to slow down progression, and so in the early stages of disease, patients will retain perfect vision for longer. Moreover, patients that have lost significant vision will be able to keep what they do have for much longer.
Could you explain the science of Tinlarebant?
ABCA4, which is the underlying gene for Stargardt disease, is one of the few amongst the about 300 known disease genes that, if mutated, can cause complete blindness, or what we call “no light perception.”
In the presence of mutations in the ABCA4 gene, vitamin A toxic byproducts form and accumulate in the retina, causing macular degeneration.
RBP4 is a protein that transports vitamin A to the eye, and Tinlarebant works by lowering RBP4 systemically. You can see from our biomarkers in the clinical trials that when patients took Tinlarebant, RBP4 went down by 80% and stayed there.
Furthermore, there is a receptor that is expressed only in the eye, and this receptor controls the eye’s access to vitamin A, which is essential for vision. As a result of reducing RBP4, vitamin A availability is reduced in the photoreceptors, but not in other organs, since they get vitamin A through other mechanisms.
So even when RBP4 is lowered systemically, other organs are unaffected because of this eye-specific receptor. That’s why you can treat patients with Tinlarebant systemically with a pill and still have an effect only in the eye. In that sense, Tinlarebant is almost as precise as gene therapy, without requiring traumatic surgery under the retina.
There may also be implications for other retinal degenerations, including age-related macular degeneration, which is why we’re running an AMD trial.
What happens next?
For clinicians, as soon as they look at the retina and see the disease, at that moment, they are suffering too—because they know what it means for the patient’s life. They must explain Stargardt disease, that it’s an inherited disease, and may therefore also affect other relatives.
I believe Tinlarebant will become the future standard of care. We are working very hard, day and night, around the world, to make this therapy available. We have breakthrough designation, as well as rolling and priority review. We will be as fast as possible. Patients need to bear with us for a year or so—but we will get there!
Read our interview with Belite Bio's Chief Executive Officer, Dr. Tom Lin
Dr. Adil Ali
What questions should we ask Hendrik next? Let us know in the comments.
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