Dicerna's most advanced GalXC™ product candidate

DCR-PHXC utilizes Dicerna’s GalXC™ technology, a proprietary platform that advances the development of next-generation RNAi-based therapies designed to silence disease-driving genes in the liver. DCR-PHXC is being tested in a variety of PHYOX trials, for the treatment of all three genetic forms of primary hyperoxaluria (PH):

  • PHYOX1 (DCR-PHXC-101): Single ascending dose study of DCR-PHXC in healthy volunteers and patients with PH 1 and 2
  • PHYOX2 (DCR-PHXC-201): Double-blind, randomized, placebo-controlled, pivotal trial (2:1 randomization) in ~36 patients with PH1 and PH2
  • PHYOX3 (DCR-PHXC-301): Long-term, multi-dose, open-label, rollover extension trial allowing readouts of multi-dose data and long-term access to DCR-PHXC for patients who previously participated in a PHYOX study

For more information about our PHYOX trials, please visit PHYOXTrials.com.

How does DCR-PHXC work?

GalXC enables subcutaneous delivery of RNAi therapies to hepatocytes in the liver and offers several distinct potential benefits, as extensively demonstrated in various animal models. Such benefits could include potent silencing of disease-causing genes like lactate dehydrogenase A (LDHA); highly specific targeting to hepatocytes, sparing other cell types in the body; a long duration of action; and a simple, infrequent dosing regimen.

In patients with PH, the liver over-produces oxalate, a metabolite that can accumulate throughout the body and particularly in the kidneys, often resulting in end-stage renal disease (ESRD) and the need for both kidney and liver transplants.

Why focus on LDHA?

Dicerna’s findings show that LDHA in animal models reduces oxalate to normal or near-normal levels in PH1 and PH2. The Company has identified LDHA as potentially being a novel therapeutic target in patients with PH:

  • LDHA inhibition reduces oxalate to normal or near-normal levels in PH types 1 and 2
  • LDHA reduction has a near-linear correlation with oxalate reduction and offers a minimal metabolic intervention. These benefits of LDHA inhibition may translate into consistent therapeutic activity even in the event of a missed dose. There are numerous case reports of LDHA deficiency naturally occurring in healthy humans, with no reported adverse effects due to deficiency in the liver
  • DCR-PHXC appeared to be well tolerated in these animal studies, with no adverse effects in the liver. Formal animal toxicology studies are ongoing

PHYOX1 Overview