The first retinal dystrophy for which Astherna aims to conduct a clinical trial is Stargardt disease.
RNA therapy consists of a solution with small molecular band-aids (AONs), which precisely fit to the area surrounding the mutation in the ABCA4-RNA. When such a band-aid binds to the RNA, it covers the mistake in the recipe, and the protein kitchen will ignore the mistake and produce a normal, functional ABCA4 protein.
More detailed information about the mode of action of RNA therapy can be found here.
More detailed information about Stargardt disease can be found here.
As a consequence of this, each ABCA4 mutation requires its own RNA therapy. The first RNA therapy Astherna develops restores a mutation that is relatively common, especially in Europe. However, this still means that this RNA therapy can only treat a subgroup of STGD1 patients. When this RNA therapy is proven effective, Astherna will continue to develop new RNA therapies for other mutations of STGD1, as well as for other inherited retinal diseases.
Moreover, Astherna’s RNA therapy is aimed to stop progression of the disease. It is unlikely that it will reverse damage that has already occurred to the retina, but is most likely to prevent further decay in vision. Therefore, it is expected that the highest benefit can be achieved in patients that still have some residual visual function.
When a treatment is shown to be effective and safe in the lab, the next step is to test the drug in patients, to determine the magnitude of a potential therapeutic effect, the best dose and risk of side-effects. This is the clinical phase, which can be further divided into three phases:
- Phase I: Safety assessment. It is determined whether a drug is safe and whether it has any unwanted side-effects
- Phase II: Dose assessment. The best dose is determined, which is both effective and safe. For this, groups of patients are given a different dose of the drug, and a comparison is made.
- Phase III: Confirmation of effectivity and safety. A requirement is set about the level of effectivity which the drug needs to meet, in order for it to be allowed for registration, by regulatory authorities. In a phase III trial, patients that are treated with the drug are compared to patients that receive a ‘fake treatment’ (placebo), in order to draw conclusions on whether the safety and efficacy requirements are met.
- After a drug has received market authorization, additional phase IV clinical trial is conducted to monitor long term safety and efficacy.