Dicerna Receives Breakthrough Therapy Designation for DCR-PHXC for Treatment of Primary Hyperoxaluria Type 1 (PH1)
Jul 15, 2019
—Designation Follows Recently Reported PHYOX™1 Phase 1 Data Showing Positive Clinical Responses to DCR-PHXC—
—FDA Recognizes Primary Hyperoxaluria Types 2 and 3 (PH2 and PH3) as Meeting Criteria for a Serious or Life-Threatening Disease or Condition—
In its communication to Dicerna, the
“By granting Breakthrough Therapy Designation, the
Dicerna recently presented updated data from the PHYOX1 Phase 1 clinical trial of DCR-PHXC, which reported substantial post-dose reductions in 24-hour urinary oxalate levels in adult and adolescent study participants with PH1 and PH2. The updated PHYOX1 data, presented at the Oxalosis and Hyperoxaluria Foundation’s
DCR-PHXC is the only RNAi investigational drug in development for the treatment of all types of primary hyperoxaluria (PH), and the most advanced product candidate utilizing Dicerna's GalXC™ 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 lactate dehydrogenase A enzyme, or 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 may 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 organs in patients with PH.
Dicerna is evaluating DCR-PHXC in the PHYOX™ clinical trial program. Interim results from the ongoing PHYOX1 Phase 1 study have demonstrated normalization or near-normalization of urinary oxalate levels in a majority of participants receiving DCR-PHXC, as well as a favorable tolerability profile.
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. The accumulation of oxalate can result in severe damage to the kidneys and other organs.
There are three known genetic types of PH, each of which results from a mutation in a specific gene. In each type, the mutation decreases the activity of an enzyme in the liver, leading to an increase in the production of oxalate.
- PH type 1, or PH1, is caused by a mutation in the AGXT gene. This causes a deficiency of the enzyme alanine:glyoxylate-aminotransferase (AGT).
- PH type 2, or PH2, is caused by a mutation in the GRHPR gene. This causes a deficiency of the enzyme glyoxylate/hydroxypyruvate reductase (GR/HPR).
- PH type 3, or PH3, is caused by a mutation in the HOGA1 gene, causing a deficiency of the enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA).2,3
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.4 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. 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 future potential for confirmation of reductions in urinary oxalate in future data from DCR-PHXC clinical trials; (ii) research and development plans and timelines related to DCR-PHXC; and (iii) the potential of Dicerna™’s technology and drug candidates in the Company’s research and development pipeline. The process by which an early stage investigational therapy such as DCR-PHXC and an early stage platform such as GalXC could potentially lead to an approved product is long and subject to highly significant risks. Applicable risks and uncertainties include those relating to Dicerna’s clinical research and other risks identified under the heading "Risk Factors" included in the Company’s most recent Form 10-Q filing and in other future filings with the
Dicerna™, GalXC™, and PHYOX™ are trademarks of
Dicerna Press Release. Dicerna™ Presents Additional Data from PHYOX™1 Study of DCR-PHXC in Patients with Primary Hyperoxaluria Type 1 (PH1) and Type 2 (PH2). Available at: http://investors.dicerna.com/news-releases/news-release-details/dicernatm-presents-additional-data-phyoxtm1-study-dcr-phxc. Accessed
July 11, 2019. 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.
Hopp, K, Cogal, A, Bergstralh, E, et al. Phenotype-genotype correlations and estimated carrier frequencies of primary hyperoxaluria.
Journal of the American Society of Nephrology2015; 26(10):2559-2570.
- 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.
Tang X, Bergstrath EJ, Mehta RA, Vrtiska TJ, Milliner DS, Lieske JC. Nephrocalcinosis is a risk factor for kidney failure in primary hyperoxaluria.
Kidney International2015; 87:623-631.