Jan 31, 2020 Press Release for Alnylam
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Alnylam Receives Positive CHMP Opinion for GIVLAARI™ (givosiran) for the Treatment of Acute Hepatic Porphyria in Adults and Adolescents
Jan 31, 2020
− European Commission Decision Expected in March −
− Positive Opinion is Based on Data from the Pivotal ENVISION Phase 3 Study −
“Today’s CHMP positive opinion is very encouraging news for patients living with acute hepatic porphyria and recognizes the potential of givosiran to address the urgent unmet need that exists for those living with this ultra-rare, inherited disease,” said
“Acute hepatic porphyria is characterized by debilitating, potentially life-threatening attacks and chronic disease manifestations that dramatically impact the lives of patients and their families,” said
The positive opinion is based on efficacy and safety findings from the pivotal ENVISION Phase 3 study, including data on the reduction in the annualized rate of composite porphyria attacks compared with placebo. Findings were presented in
Givosiran was granted Priority Medicines (PRIME) Designation by the EMA as well as Orphan Designation in the
About Givosiran
Givosiran is an investigational, subcutaneously administered RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) in development for the treatment of acute hepatic porphyria (AHP). Monthly subcutaneous administration of givosiran has the potential to significantly lower induced liver ALAS1 levels in a sustained manner and thereby decrease neurotoxic heme intermediates, aminolevulinic acid (ALA), and porphobilinogen (PBG), toward normal levels. By reducing accumulation of these intermediates, givosiran has the potential to prevent or reduce the occurrence of severe and life-threatening attacks, control chronic symptoms, and decrease the burden of the disease. Givosiran utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC) GalNAc conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index.
About ENVISION Phase 3 Study
The ENVISION Phase 3 trial was a randomized, double-blind, placebo-controlled, global, multicenter study to evaluate the efficacy and safety of givosiran in patients with a documented diagnosis of acute hepatic porphyria (AHP). The primary endpoint was reduction relative to placebo in the annualized rate of composite porphyria attacks, defined as those requiring hospitalization, urgent healthcare visit, or hemin administration at home, in patients with acute intermittent porphyria (AIP, the most common subtype of AHP) over six months. Key secondary and exploratory endpoints evaluated reductions in neurotoxic heme intermediates, aminolevulinic acid (ALA) and porphobilinogen (PBG), usage of hemin, symptoms of AHP, such as pain, nausea, and fatigue, as well as impact on quality of life. The trial enrolled 94 patients with AHP, at 36 study sites in 18 countries around the world and is the largest-ever interventional study conducted in AHP. Patients were randomized 1:1 to givosiran or placebo, with givosiran administered subcutaneously at 2.5 mg/kg monthly. Upon completion of dosing in the double-blind period, all eligible patients (99 percent) enrolled in the ENVISION open-label extension (OLE) to receive givosiran on an ongoing basis.
About Acute Hepatic Porphyria
Acute hepatic porphyria (AHP) refers to a family of ultra-rare, genetic diseases characterized by debilitating, potentially life-threatening attacks and, for some patients, chronic manifestations that negatively impact daily functioning and quality of life. AHP is comprised of four subtypes: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and ALA dehydratase-deficiency porphyria (ADP). Each type of AHP results from a genetic defect leading to deficiency in one of the enzymes of the heme biosynthesis pathway in the liver. AHP disproportionately impacts women of working and childbearing age; symptoms of the disease vary widely. Severe, unexplained abdominal pain is the most common symptom, which can be accompanied by limb, back or chest pain, nausea, vomiting, confusion, anxiety, seizures, weak limbs, constipation, diarrhea, or dark or reddish urine. The nonspecific nature of AHP signs and symptoms can often lead to misdiagnoses of other more common conditions, such as viral gastroenteritis, irritable bowel syndrome (IBS), addiction withdrawal, and appendicitis. Consequently, patients with AHP can wait up to 15 years for a confirmed diagnosis. In addition, long-term complications and comorbidities of AHP can include hypertension, chronic kidney disease, or liver disease, including hepatocellular carcinoma. Currently, there are no treatments approved in
About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.
About 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 approval of GIVLAARI™ (givosiran) injection for subcutaneous use, and the implications of such approval for patients and their caregivers, the results of the ENVISION Phase 3 clinical trial for givosiran, expectations regarding the review of GIVLAARI’s marketing authorization application under accelerated assessment by the EMA for the treatment of patients with AHP, and expectations regarding its “Alnylam 2020” guidance for the advancement and commercialization of RNAi therapeutics constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties, and other factors, including, without limitation, Alnylam’s ability to discover and develop novel drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its product candidates, the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all, actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation, and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing, delays, interruptions, or failures in the manufacture and supply of its product candidates, obtaining, maintaining, and protecting intellectual property, Alnylam’s ability to enforce its intellectual property rights against third parties and defend its patent portfolio against challenges from third parties, obtaining and maintaining regulatory approval, pricing and reimbursement for products, including GIVLAARI, progress in establishing a commercial and ex-
View source version on businesswire.com: https://www.businesswire.com/news/home/20200131005020/en/
Source:
Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom
(Investors and Media)
+1-617-682-4340
Josh Brodsky
(Investors)
+1-617-551-8276
Fiona McMillan
(Media, Europe)
+44 1628 244960
For Media Inquiries, please contact:
Christine Lindenboom
SVP, Investor Relations & Corporate Communications media@alnylam.com 617-682-4340
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