Pipeline

Novel Investigational Drug for PH: DCR-PHXC

DCR-PHXC: Dicerna's most advanced GalXC product candidate

DCR-PHXC: 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. In December 2017, we initiated human dosing in normal healthy volunteers (NHVs) in a Phase 1 clinical trial of DCR-PHXC, called PHYOX, and dosed the first patient with PH in May 2018.

For more information about PHYOX and Dicerna’s plans for the DCR-PHXC development program, click here.

How DCR-PHXC works

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.

Dicerna presented research findings on LDHA inhibition, which was shown in animal models to reduce oxalate to normal or near-normal levels in PH types 1, and 2. The Company has identified as potentially being a novel therapeutic target in patients with PH. Highlights included:

  • 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.

DCR-PHXC Overview

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