ProQR’s work development program for sepofarsen in Leber...

ProQR’s work development program for sepofarsen in Leber congenital amaurosis 10 (LCA) has been already been discussed a few times on this forum (including here, here, here, here and here) and was specifically referenced by the Company almost two years ago, when it was noted that PYC had achieved efficacy in animal models at substantially lower doses than ProQR’s non-CPP assisted ASO therapy.

While both drugs target a type of Retinitis Pigmentosa, there are differences between the VP-001 and sepofarsen programs.

VP-001 is being developed in the indication of an autosomal dominant type of Retinitis Pigmentosa – RP11, in which a mutation occurs in the gene, PRPF31. Sepofarsen is targeting Leber's Congenital Amaurosis (LCA) due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene. PYC’s indication is said to represent 1.5 -3% of the RP population whereas ProQR’s addresses approximately 1% of the RP population.

VP-001 dosage will likely be lower than that of sepofarsen. The target registration dose used in the sepofarsen Phase 1/2 clinical trial was a 160µg loading dose followed by 80µg doses at intervals, although a 320µg loading dose/160µg interval dose was also assessed. It is unclear which dose level was received as a single injection by the “eleventh patient” who was reported to have gained vision for more than a year.

One could argue that ProQR’s progress and success to date are a positive for PYC, because it provides validation of the antisense approach in inherited retinal disease.