FDA Grants Breakthrough Therapy Designation for Alnylam's Givosiran for the Prophylaxis of Attacks in Patients with Acute Hepatic Porphyria
- Additional Phase 1 Results to be Presented at the
- Company Plans to Initiate Phase 3 Clinical Program in Late 2017 -
"Patients with acute hepatic porphyrias, a family of ultra-rare
diseases, suffer from severe neurovisceral attacks often resulting in
hospitalization, and chronic, debilitating symptoms that impair daily
Promising results from the ongoing Phase 1 study of givosiran
demonstrating meaningful reductions in the occurrence of porphyria
attacks formed the basis of the Breakthrough application. Updated
results from this trial will be provided in an oral presentation on
About Givosiran Phase 1 Study
The ongoing portion of the Phase 1 study of givosiran (Part C) is being conducted as a randomized, double-blind, placebo-controlled study. Data presented at the 2016
Alnylam is developing givosiran (formerly known as ALN-AS1), a subcutaneously administered, investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias, including acute intermittent porphyria (AIP). AIP is the most common of the porphyrias, an ultra-rare autosomal dominant disease caused by loss of function mutations in porphobilinogen deaminase (PBGD), an enzyme in the heme biosynthesis pathway that can result in accumulation of toxic heme intermediates, including aminolevulinic acid (ALA) and porphobilinogen (PBG). Givosiran is an ESC-GalNAc-siRNA conjugate targeting ALAS1, a liver-expressed, rate-limiting enzyme upstream of PBGD in the heme biosynthesis pathway. Inhibition of ALAS1 is known to reduce the accumulation of heme intermediates that cause the clinical manifestations of AIP. Givosiran has the potential to be a novel treatment approach for the prevention of recurrent attacks. Givosiran has previously been granted PRIME designation which was established by the
About Acute Hepatic Porphyrias
The porphyrias are a family of rare metabolic disorders with mostly autosomal dominant inheritance predominantly caused by a genetic mutation in one of the eight enzymes responsible for heme biosynthesis. Acute hepatic porphyrias (AHP) constitute a subset where the enzyme deficiency occurs within the liver, and includes acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). Exposure of AHP patients to certain drugs, dieting, or hormonal changes can trigger strong induction of aminolevulinic acid synthase 1 (ALAS1), another enzyme in the heme biosynthesis pathway, which can lead to accumulation of neurotoxic heme intermediates that precipitate disease symptoms. Patients with AHP can suffer from a range of symptoms that, depending on the specific type, can include acute and/or recurrent life-threatening attacks with severe abdominal pain, peripheral and autonomic neuropathy, neuropsychiatric manifestations, cutaneous lesions and possibly paralysis and death if untreated or if there are delays in treatment. There are no approved treatments for the prevention of attacks; the only approved treatment for acute attacks is hemin for injection (Panhematin® or Normosang®), a preparation of heme derived from human blood. Hemin requires administration through a large vein or a central intravenous line and is associated with a number of complications including thrombophlebitis or coagulation abnormalities. Chronic administration of hemin may result in renal insufficiency, iron overload, systemic infections (due to the requirement for central venous access) and, in some instances, tachyphylaxis.
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
Alnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of patients who have limited or inadequate treatment options. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust discovery platform and deep pipeline of investigational medicines, including three product candidates that are in late-stage development or will be in 2017. Looking forward, Alnylam will continue to execute on its "Alnylam 2020" strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam.
Alnylam Forward Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including givosiran, its expectations regarding the timing of clinical studies, including the initiation of a Phase 3 trial for givosiran following interactions with regulatory authorities, its expectations regarding scientific and regulatory support for givosiran from the
The scientific information referenced in this news release relating to
givosiran is preliminary and investigative. Givosiran has not been
approved by the
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