Dicerna Pharmaceuticals, a RNA interference-based biopharmaceutical company, has dosed the first patient in its DCR-PH1-101 trial, which is the first Phase l clinical trial of DCR-PH1 to treat primary hyperoxaluria type 1 (PH1).
PH1 is a severe, rare, inherited disorder of the liver and often results in kidney failure.
There are currently no approved therapies for the disease.
Dicerna noted that the US Food and Drug Administration (FDA) designated DCR-PH1, an investigational Dicer substrate short interfering RNA (DsiRNA) therapeutic, as an orphan drug in April last year.
Last August, the European Medicines Agency (EMA) granted orphan drug designation to DCR-PH1 in the European Union (EU).
In patients with PH1, the liver over-produces oxalate, a metabolite that can accumulate throughout the body and particularly in the kidneys, often led to end-stage renal disease (ESRD) and the need for both kidney and liver transplants.
DCR-PH1 is currently being developed by Dicerna, targets rare diseases of the liver and is based on the company's proprietary DsiRNA-EX technology.
In a genetic mouse model of PH1, DCR-PH1 markedly knocked down HAO1, the gene transcript that encodes for the enzyme glycolate oxidase (GO), causing near normalisation of oxalate levels.
In preclinical models, DCR-PH1 also helped increasing the excretion of glycolate, a metabolite that is the substrate of the GO enzyme, and as a result, a pharmacodynamic marker of effective knockdown.
The DCR-PH1-101 clinical trial is testing single ascending doses of DCR-PH1 in patients who have a genetically confirmed diagnosis of PH1.
Investigators will monitor patients for changes in urinary and plasma glycolate and oxalate, which are major efficacy markers in PH1.
Once safety has been demonstrated with single doses, the trial will transition to a multi-dose study that will include a pharmacokinetic analysis to identify an appropriate dose for future studies of DCR-PH1.
Dicerna Pharmaceuticals chief medical officer Dr Pankaj Bhargava said: "Dosing of our first patient with PH1 is an important milestone for DCR-PH1, as it brings us a step closer to offering a potentially meaningful therapeutic option to this underserved patient population.
"We eagerly await the first clinical readout from this study, as well as from the normal healthy volunteer study, and we look forward to sharing the results with the PH1 community."