Andrew,
A PMO is just one type of ASO (antisense oligonucleotide). There are numerous ASO types– this recent paper,
Antisense Oligonucleotides: A Primer, provides further details.
Today’s announcement makes reference to “similar pre-clinical studies of ‘naked’ Anti-Sense Oligonucleotides” in which an approximately 60 times higher dose was administered than the 1.6 mcg dose used in PYC’s study.
The provided reference in today’s announcement points to the pre-clinical studies completed by Dutch biotech
ProQR and their antisense drug, sepofarsen (QR-110), which is intended for the treatment of the inherited retinal disease, Leber’s congenital amaurosis (LCA) type 10. In ProQR’s pre-clinical mouse study of sepofarsen, a 100 mcg dose was used.
Following up what happened after that study, I see that Pro QR proceeded to a Phase 1/2 study, which commenced in October 2017. The ten patients in the
study were to receive four intravitreal injections of sepofarsen; one injection every three months. Two dose levels were tested in this study, 80 mcg (160 mcg loading dose) and 160 mcg (320 mcg loading dose). Primary completion was supposed to be in December 2019, but after an interim analysis,
the trial was halted early in September 2018. Citing a “rapid and sustained benefit on every metric of vision assessed” in the early trial, the company announced it would move quickly to a pivotal Phase 2/3 trial. The announcement was well received by the market, adding $300 million to the value of Pro QR.
That pivotal trial commenced in April this year.
The two year trial, in an initial 30 patients, is testing doses of 40 mcg and 80 mcg of sepofarsen, with the second dose administered three months after the first and subsequent doses administered every six months. The decision to run with an even lower dose in this pivotal trial may relate to the fact that
CME (macular edema) was seen in the higher dose group (160mcg) in the Phase 1/2 trial.
Results to date are looking good for PYC. From this point, I expect that a longer time-course evaluation will be required (3 months?). Also, while the sustained effect at much lower dose achieved by PYC is impressive, I wish I had a clearer picture of the exon-skipping efficacy of the PYC CPP-ASO at the 1.6mcg dose level, versus that achieved in “similar pre-clinical studies” at 100mcg dosage.
(20min delay)