"The IND submission is an important milestone for the DCR-PH1 program,
as it takes us one step closer to bringing this novel therapy to
patients with primary hyperoxaluria type 1," said
DCR-PH1 incorporates small interfering RNA (siRNA) formulated in a
proprietary lipid nanoparticle (LNP) technology that is being
investigated as a system for efficient delivery to the liver after
intravenous (IV) administration. Dicerna obtained rights to this
delivery technology by way of a licensing agreement with Arbutus
Biopharma Corporation, formerly
About Primary Hyperoxaluria Type 1 (PH1)
PH1 is a rare, inherited genetic disorder of the AGXT gene in the liver which causes excess oxalate production.1 The AGXT gene encodes for the liver enzyme alanine:glyoxylate-aminotransferase (AGT). The kidneys are unable to eliminate the large amount of oxalate that is produced and the accumulation can result in severe damage to the kidneys and other organs. Currently, there are no approved therapies for the treatment of PH1 in the US and the EU.
Patients with this disease often undergo combined liver and kidney transplant, a major surgical procedure, and subsequently must take immunosuppressant drugs for the rest of their lives, and there is a potential for a future re-transplant and possible cancers. 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. The estimated genetic prevalence of PH1 is 1 in 151,887, which suggests more than 5,000 patients in the US and EU.2 The median age at first symptoms is 5.8 years.3 The median age at diagnosis is between 4.2 and 11.5 years depending on whether or not nephrocalcinosis is present.4 Fifty percent of patients with PH1 reach ESRD by their mid-30s.5
Dicerna is developing DCR-PH1, which is in preclinical development, for the treatment of PH1. DCR-PH1 is engineered to address the pathology of PH1 by targeting and destroying the messenger RNA (mRNA) produced by HAO1, a gene implicated in the pathogenesis of PH1. HAO1 encodes glycolate oxidase (GO), an enzyme involved in producing oxalate. This approach seeks to prevent the complications of PH1 through the reduction of oxalate production. In preclinical studies, DCR-PH1 induced inhibition of HAO1 and significantly reduced levels of urinary oxalate in animal models of PH1.
About Dicerna's Dicer Substrate Technology
Dicerna's proprietary RNAi molecules are known as Dicer substrate short-interfering RNA molecules, or DsiRNAs, so called because they are processed by the Dicer enzyme, which is the initiation point for RNAi in the human cell cytoplasm. Dicerna's discovery approach seeks to maximize RNAi potency through development of DsiRNAs that are thought to be ideally structured for processing by Dicer. Dicer processing enables the preferential use of the correct RNA strand of the DsiRNA, which may increase the efficacy of the RNAi mechanism, as well as the potency of the DsiRNA molecules relative to other molecules used to induce RNAi.
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. DCR-PH1 is in preclinical development, and
the process by which a preclinical therapeutic candidate could
potentially lead to an approved drug is long and subject to significant
risks and uncertainties. The Investigational New Drug application does
not assure a faster or more probable regulatory path. Applicable risks
and uncertainties include those relating to our preclinical and clinical
research and other risks identified under the heading "Risk Factors"
included in our most recent Form 10-Q filing and in other future filings
1. Cochat, P, Rumsby, G. Primary Hyperoxaluria.
2. Hopp, K, Cogal, A, Bergstralh, E, Seide, B, Olson, J, Meek, A,
Lieske, J, Milliner, D and Harris, C on behalf of the
3. 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.
4. Tang X, Bergstrath EJ, Mehta RA, Vrtiska TJ, Milliner DS, Lieske JC.
Nephrocalcinosis is a risk factor for kidney failure in primary
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