Investors & Media
Dicerna Announces Late-Breaking Data from the PHYOX Phase 1 Clinical Trial of DCR-PHXC Will Be Presented at ASN Kidney Week 2018
Details for the poster presentation are as follows:
- Session Title: Late-Breaking Clinical Trials Posters [LB-PO]
- Poster Title:PHYOX: A Safety and Tolerability Study of DCR-PHXC in Primary Hyperoxaluria Types 1 and 2
- Poster Number: TH-PO1167
Thursday, October 25, 2018, 10:00 a.m. - 12:00 p.m. PT
- Presenter: Dr.
Bernd Hoppe, M.D., PHYOX investigator and head of the Division of Pediatric Nephrologyin the Department of Pediatricsat the University of Bonn, Germany
The Company recently reported initial proof-of-concept data from the PHYOX Phase 1 trial demonstrating significant and sustained reduction in urinary oxalate levels following single-dose administration in adults with PH1 and PH2.
For information on ASN Kidney Week 2018, visit https://www.asn-online.org/education/kidneyweek/.
DCR-PHXC is an investigational drug in development for the treatment of all forms of primary hyperoxaluria (PH), and the most advanced product candidate utilizing Dicerna's GalXCTM technology. GalXC is a proprietary platform invented by Dicerna scientists to discover and develop next-generation RNAi-based therapies designed to silence disease-driving genes in the liver. In animal models of PH, DCR-PHXC selectively silences lactase dehydrogenase (LDHA) in the liver, blocking the excess production of oxalate, a hallmark of the disease. In preclinical studies of DCR-PHXC, the compound was well tolerated with no adverse effects in the liver. Studies have shown that people who are completely deficient in LDHA show no liver dysfunction and can lead normal lives. LDHA deficiency in the liver might be beneficial for patients with PH, as the LDHA enzyme is implicated in the abnormal production of oxalate in PH, which in turn is responsible for the severe damage to kidneys and other organ systems in patients with PH.
About Primary Hyperoxaluria (PH)
Primary hyperoxaluria (PH) is a family of severe, rare, genetic liver disorders characterized by overproduction of oxalate, a natural chemical in the body that is normally eliminated as waste through the kidneys. In patients with PH, the kidneys are unable to eliminate the large amount of oxalate that is produced, and the accumulation of oxalate can result in severe damage to the kidneys and other organs. Currently, there are no approved therapies for the treatment of PH.
There are three known types of PH, each of which results from a mutation in a specific gene, as well as PH for which the molecular basis remains unknown, often referred to as idiopathic PH (IPH) or "no mutation detected" (NMD) PH. The known PH mutations cause a decrease in the activity of a specific enzyme in the liver, triggering an increase in oxalate production. In each case the decreased enzyme activity changes the balance of intermediary metabolites, resulting in overproduction of oxalate. The three genetically known types of PH are: 1,2
- PH1, which is caused by a mutation in the AGXT gene, causing a deficiency of the enzyme alanine:glyoxylate-aminotransferase (AGT)
- PH2, which is caused by a mutation in the GRHPR gene, causing a deficiency of the enzyme glyoxylate/hydroxypyruvate reductase (GR/HPR)
- PH3, which is caused by a mutation in the HOGA1 gene, causing a deficiency of the enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA)
Patients with severe PH often undergo both liver and kidney transplants, which are major surgical procedures, and subsequently must take immunosuppressant drugs for the rest of their lives. Patients with decreased renal function may also experience oxalosis, which involves a build-up of oxalate in other organs such as the bone, skin, heart, and retina, possibly causing other concomitant, debilitating complications.
PH occurs in an estimated 1 in 120,000 live births around the world.3 The
estimated genetic prevalence of PH1 is 1 in 151,887 births, which
implies more than 5,000 patients in the
Cautionary Note on Forward-Looking Statements
This press release includes forward-looking statements. Such
forward-looking statements are subject to risks and uncertainties that
could cause actual results to differ materially from those expressed or
implied in such statements. Examples of forward-looking statements
include, among others, statements we make regarding: (i) the therapeutic
and commercial potential of the GalXC™ platform, including DCR-PHXC;
(ii) research and development plans related to GalXC,™ including
DCR-PHXC; and (iii) the potential of our technology and drug candidates
in our research and development pipeline. The process by which an early
stage platform such as GalXC (including DCR-PHXC, our lead product
candidate) could potentially lead to an approved product is long and
subject to highly significant risks. In general, most earlier stage drug
candidates do not ultimately become approved drugs. Applicable risks and
uncertainties include those relating to Dicerna's clinical and
preclinical research and others identified under the heading "Risk
Factors" included in the Company's filings with the
Oxalosis & Hyperoxaluria Foundation. Overview of hyperoxaluria. 2017. Available at: https://ohf.org/overview/. Accessed July 6, 2017.
Rare Kidney Stone Consortium. Primary hyperoxaluria. 2010. Available at: http://www.rarekidneystones.org/hyperoxaluria/physicians.html. Accessed July 6, 2017.
|3.||Hopp, K, Cogal, A, Bergstralh, E, et al. Phenotype-genotype correlations and estimated carrier frequencies of primary hyperoxaluria. Journal of the American Society of Nephrology 2015; 26(10):2559-2570.|
|4.||van der Hoeven SM, van Woerden CS, Groothoff JW. Primary hyperoxaluria type 1, a too often missed diagnosis and potentially treatable cause of end-stage renal disease in adults: results of the Dutch cohort. Nephrology, Dialysis, Transplantation 2012; 27(10):3855-3862.|
|5.||Tang X, Bergstrath EJ, Mehta RA, Vrtiska TJ, Milliner DS, Lieske JC. Nephrocalcinosis is a risk factor for kidney failure in primary hyperoxaluria. Kidney International 2015; 87:623-631.|