The Orphan Drug Designation program, administered by the FDA's
"The Orphan Drug Designation is an important regulatory milestone as we
further our development of DCR-PH1 in PH1, a disease that currently does
not have an approved treatment option," said
DCR-PH1 incorporates a proprietary, lipid nanoparticle (LNP) technology
which allows it to be efficiently delivered to the liver after
intravenous (IV) administration. Dicerna obtained rights to this
delivery technology by way of a licensing agreement signed in
About Primary Hyperoxaluria Type 1 (PH1)
PH1 is a rare, inherited liver disorder in which excess oxalate
production often results in severe damage to the kidneys. The disease
can be fatal unless the patient undergoes a liver-kidney transplant, a
major surgical procedure that is often difficult to perform due to the
lack of donors and the threat of organ rejection. In the event of a
successful transplant, the patient must live the rest of his or her life
on immunosuppressant drugs, which have substantial associated risks.
Currently, there are no
PH1 is characterized by a genetic deficiency of the liver enzyme alanine:glyoxalate-aminotransferase (AGT), which is encoded by the AGXT gene. AGT deficiency induces overproduction of oxalate by the liver, resulting in the formation of crystals of calcium oxalate in the kidneys. Oxalate crystal formation often leads to chronic and painful cases of kidney stones and subsequent fibrosis (scarring), which is known as nephrocalcinosis. Many patients progress to end-stage renal disease (ESRD) and require dialysis or transplant. Aside from having to endure frequent dialysis, PH1 patients with ESRD may experience a build-up of oxalate in the bone, skin, heart and retina, with concomitant debilitating complications. While the true prevalence of primary hyperoxaluria is unknown, it is estimated to be one to three cases per one million people.1 Fifty percent of patients with PH1 reach ESRD by their mid-30s.2
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, a protein involved in producing oxalate. By reducing oxalate production, this approach seeks to prevent the complications of PH1. In preclinical studies, DCR-PH1 has been shown to induce potent and long-term inhibition of HAO1 and to significantly reduce levels of urinary oxalate, while demonstrating long-term efficacy and tolerability 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 is believed to maximize RNAi potency because the DsiRNAs are structured to be ideal 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. Orphan Drug Designation 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-K filing and in other future filings
1 Cochat, P, Rumsby, G. Primary hyperoxaluria.
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