RTx-015: Exploring Optogenetic Gene Therapy for RP and Choroideremia
Ray Therapeutics, a clinical stage biopharmaceutical company, is currently investigating their lead optogenetic therapy candidate, RTx-015, in early stage clinical trials for those with RP and Choroideremia.
In a nutshell:
RP and choroideremia are inherited retinal diseases that cause progressive vision loss by damaging the retina, although through different mechanisms. RTx-015 is an investigational optogenetic gene therapy being developed for people with advanced RP or choroideremia, aiming to enable remaining retinal cells to respond to light after photoreceptors have degenerated. It is currently being evaluated in an early-stage Phase 1 clinical trial focused on safety and dose finding, with participants receiving a single injection and being followed for five years. While RTx-015 has received regulatory designations to help speed its development, it remains in the early stages of research and will require further testing and regulatory approval before it could become widely available.
What is RP?
RP is one of the most common types of inherited retinal disease (IRD), associated with faults in over 100 genes, affecting around 1 in 4,000 people globally. RP causes progressive vision loss, starting peripherally, due to the loss of light-sensing photoreceptor cells in the retina. To learn more, please watch this short animation video on Inherited Retinal Disease
What is Choroideremia?
Choroideremia is an IRD that causes damage to the network of blood vessels behind the retina that are known as the choroid. The choroid supplies oxygen and nutrients to support and nourish the retinal pigment epithelial (RPE) cells and the photoreceptor cells. Choroideremia is likely to be underdiagnosed as its symptoms are quite similar to a number of other retinal conditions such as RP. The distinctive appearances of the back of the eye and X-linked inheritance pattern can help doctors to make the diagnosis.
Choroideremia is most often caused by mutations in a gene called CHM. So far, there have been 280 mutations identified in the CHM gene that can result in choroideremia.
What is RTx-015?
RTx-015 is an investigative optogenetic gene therapy in development for RP and Choroideremia. Optogenetic therapy is not dependent on genetic diagnosis but is only appropriate for advanced stages of sight loss. It works by using gene therapy techniques to provide cells at the back of the eye with the genetic instructions to build a light sensitive protein. These cells do not normally sense light but could potentially take over from degenerated photoreceptors.
In this case, RTx-015 is designed to deliver a bioengineered, highly light-sensitive protein to retinal ganglion cells (the output nerve cells of the retina that transmit visual information to the brain via the optic nerve). These modified cells can then detect light and send visual signals to the brain, potentially bypassing the lost photoreceptors. While this cannot replace healthy photoreceptors or restore normal vision, it may help recover useful visual function in people with advanced retinal degeneration.
The trial:
This phase 1 trial is taking place across 4 sites in the U.S and is an open-label, non-randomized and dose escalation study involving 18 participants with RP or Choroideremia. This means that both participants and researchers know who is getting which treatment dose and there is no placebo group. It also means that the dose is gradually increased across groups of participants. In early-stage clinical trials, this is common because the main focus is on safety and trying to identify the dose that is the most effective and safe.
Participants will receive a single, unilateral intravitreal injection (an injection into the jelly-like substance of the eye) of RTx-015 in the study eye and be followed for a total of 5 years. Although an intravitreal injection sounds scary, the eye is numbed with anaesthetic drops before the procedure takes place and the injection part only lasts a few seconds. This means that the main sensation is a brief feeling of pressure and discomfort rather than pain. It is common to feel some soreness and irritation as the anaesthetic wears off, but this shouldn’t last longer than a few days.
What next:
RTx-015 has received multiple regulatory designations to support faster development, though it remains in early-stage testing and requires further rigorous research before it could become widely available.
RTx-015 has been granted Priority Medicines (PRIME – Europe) and Regenerative Medicine Advanced Therapy (RMAT – U.S) designations which are designed to expedite the normally lengthy review process. However, different regulatory bodies operate in the US, UK, Europe and elsewhere, and designations do not transfer across regions. Obtaining regulatory approval can take a long time, even if Ray Therapeutics seeks to work with all of them and reaching agreement for NHS availability is a further, separate process. We look forward to hearing an update from Ray Therapeutics when preliminary data from this early stage trial becomes available.
Ray Therapeutics also have a second optogenetic therapy candidate in development that targets retinal bipolar cells in Stargardt disease and other macular degenerative conditions. This is in late-stage preclinical development.
To learn more about Ray Therapeutics or RTx-015 please visit their website here.