Porphyria, Variegate

-- GIVLAARI reduces Chronic Pain, Improves Quality of Life and is the First and Only Therapy Proven to Prevent AHP Attacks -- TORONTO, Oct. 18, 2021 /CNW/ - Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) is pleased to announce that GIVLAARI® (givosiran) has now received a positive recommendation for reimbursement from the Canadian Agency for Drugs and Technologies in Health (CADTH). GIVLAARI® is approved by Health Canada for subcutaneous use for the treatment of acute hepatic porphyria (AHP) in adults.1 "The Health Canada market authorization of GIVLAARI provides new hope for those living with AHP. For the first time, all patients have a treatment option specifically targeted for this rare and serious disease," says Colleen Coxson, Country General Manager, Alnylam Pharmaceuticals. "We are proud of what's been accomplished and are working towards full national reimbursement so that patients across Canada can have access to a treatment that will improve their overall health and quality of life." AHP is an ultra-rare condition in which patients can experience debilitating attacks of severe abdominal pain, vomiting and seizures. It can be life-threatening due to the possibility of paralysis and respiratory arrest during attacks. Many patients also experience chronic symptoms, including severe pain, which continues to be present between attacks, linked to increased rates of liver cancer, kidney failure and hypertension.2, 3 "Patients suffering from this very rare, genetic disease often require urgent healthcare assistance and hospitalization, due to serious symptoms such as porphyria attacks which can involve severe abdominal pain, vomiting, breathing problems, seizures, and can lead to long term complications like chronic pain, chronic kidney failure and liver damage," says Dr. Colin Van Zoost MD, FRCPC, Assistant Professor of Medicine Dalhousie University. "Not knowing when the next attack will can cause severe anxiety for many patients, making engagement in day-to-day life, work and social situations difficult. GIVLAARI® gives us a treatment option that can help patients avoid ever having another attack, allowing them to re-engage with society and live as close to a normal life as possible." The positive recommendation for reimbursement was supported by the results of the ENVISION Phase 3 Study, a randomized, double-blind, placebo-controlled, global, multicenter study to evaluate the efficacy and safety of GIVLAARI® in patients with a documented diagnosis of acute hepatic porphyria (AHP).4 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 intravenous hemin administration at home, in patients with acute intermittent porphyria (AIP, the most common subtype of AHP) over six months.5 Full details on the recommendation is available on the CADTH website.6 About GIVLAARI® (givosiran) GIVLAARI® is an RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of adults with acute hepatic porphyria (AHP). In the pivotal study, givosiran was shown to significantly reduce the rate of porphyria attacks that required hospitalizations, urgent healthcare visits or intravenous hemin administration at home compared to placebo. GIVLAARI is Alnylam's first commercially available therapeutic based on its Enhanced Stabilization Chemistry ESC-GalNAc conjugate technology to increase potency and durability. GIVLAARI is administered via subcutaneous injection once monthly at a dose based on actual body weight and should be administered by a healthcare professional. GIVLAARI works by specifically reducing elevated levels of aminolevulinic acid synthase 1 (ALAS1) messenger RNA (mRNA), leading to reduction of toxins associated with attacks and other disease manifestations of AHP. 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 a lack of certain enzymes needed to produce heme in the liver, which leads to an accumulation of porphyrins in the body to toxic amounts. AHP disproportionately impacts women of working and childbearing age, and 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. AHP is life-threatening due to the possibility of paralysis and respiratory arrest during attacks. The nonspecific nature of AHP signs and symptoms can often lead to misdiagnoses of other more common conditions such as gynecological disorders, viral gastroenteritis, irritable bowel syndrome (IBS), and appendicitis. Consequently, on a global perspective, patients with AHP can wait up to 15 years for a confirmed diagnosis, with the risk of addiction problems. In addition, long-term complications and comorbidities of AHP can include hypertension, chronic kidney disease or liver disease, including hepatocellular carcinoma. 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. About Alnylam Pharmaceuticals Alnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a new class of innovative medicines with the potential to improve the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS) diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust discovery platform. Alnylam has a deep pipeline of investigational medicines, including five product candidates that are in Phase 3 clinical trials and one in registration. 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 to address the needs of patients who have limited or inadequate treatment options. Alnylam employs over 1,200 people worldwide and is headquartered in Cambridge, MA. Alnylam Canada is headquartered in Mississauga, Ontario with established operations since June 2018. SOURCE Alnylam Pharmaceuticals, Inc. Company Codes: NASDAQ-NMS:ALNY

High prevalence rate of clinical acute intermittent porphyria attributed to high chances of genetic mutations is likely to enhance advanced APH therapeutics uptake Fact.MR, Rockville MD: Award winning consulting firm Fact.MR’s ongoing acute hepatic porphyria (APH) market study forecasts a relatively positive outlook through 2021 and beyond, on the back of increasing demand for advanced therapeutic approaches for treating metabolic disorders. The market received a significant boost amidst the COVID-19 pandemic as well. According to the National Center for Biotechnology Information, global prevalence of acute hepatic porphyria is projected to range from one in 500 to one in 50,000 individuals. The presence of clinical acute intermittent porphyria is reported to be 5 to 10 per 100,000 individuals, while prevalence of genetic mutations of AIP is around 1 in 1675 individuals. Such high prevalence rate is likely to drive demand for treating APH in forthcoming years. As per Fact.MR’s study, the acute hepatic porphyria market is expecting to witness credible developments with respect to availability of novel therapeutic drugs. In 2019, for instance, the US Food & Drug Administration (FDA) approved Givosiran (Givlaari) for adults with acute hepatic porphyrias. Givosiran is a small-interfering RNA that causes degradation of aminolevulinate synthase 1 (ALAS1) mRNA in hepatocytes through RNA interference, reducing elevated levels via subcutaneous injection. “As the global population base widens, prevalence rates of key metabolic disorders such as APH are registering a significant incline. Manufacturers are deepening their foray across emerging markets in the developing world on the back of maximum concentration of such an expansion across these countries,” says the Fact.MR analyst. Request a report sample to gain comprehensive insights at Key Takeaways from Fact.MR’s Hepatic Porphyria (APH) Market Study Acute Intermittent Porphyria (AIP) treatment to emerge as the dominant indication type By drug type, intravenous hemin administration to remain the preferred route Hospital pharmacies to be the primary distribution channel for major acute hepatic porphyria drugs US to be a potential AHP drug market, attributed to swift drug candidate approvals by the FDA Asymptomatic manifestation of the disease to fuel accelerated research on advanced AHP detection in the UK Germany and France to open new expansion frontiers amid increasing healthcare spending Acute Hepatic Porphyria (APH) Market- Prominent Drivers Rapid advancements in metabolic disorders diagnostics is likely to propel acute hepatic porphyria market growth Increasing regulatory approvals to admit possible life saving therapeutic approaches is widening growth scope Strong government support for funding advanced research is providing major boost to APH therapeutics Acute Hepatic Porphyria (APH) Market- Key Restraints Limited awareness and inadequate access to quality healthcare in developing regions is limiting uptake Asymptomatic manifestation of the disorder causes delays in diagnosis, restricting uptake Discover more about the acute hepatic porphyria market with figures and data tables, along with the table of contents. You will also find detailed market segmentation on Competitive Landscape The global acute hepatic porphyria (APH) market comprises of the following key players: Recordati Rare Diseases Inc., Lundbeck Inc., Alleviare Life Sciences Pvt. Ltd., and Alnylam Pharmaceuticals, Inc. to name a few. The aforementioned players primarily concentrate on offering advanced drug formulations which are approved by key regulatory authorities. Moreover, some players are also involved in offering resources to better understand disease onset and prognosis. For example, Alnylam Pharmaceuticals Inc., offers the PinpointAHP® platform. This forum provides patients and caregivers a variety of resources to help them understand the types of acute hepatic porphyria and recognize the signs and symptoms. Also, manufacturers are in tandem with government initiatives to rein in the incidence of prominent rare disorders. For instance, Recordati Rare Diseases Inc. is supporting the European Porphyria Network in developing information for patients and families. This helps individuals detect signs early on and take effective preventive measures to mitigate its impact. More Insights on the Acute Hepatic Porphyria (APH) Market The research study on the acute hepatic porphyria (APH) market by Fact.MR includes an in-depth analysis of major demand-driving factors and trends and a comprehensive evaluation of crucial aspects that are projected to carve growth. Market statistics have been elucidated based on indication (acute intermittent porphyria (AIP), variegate porphyria (VP), hereditary coproporphyria (HC) and hereditary deficit of delta-aminolevulinic acid dehydratase (HDAD) drug type (intravenous hemin, carbohydrate nutrition and hydration, hypertonic saline and anti-epileptics (short-acting)) and distribution channel (hospital pharmacies, drug stores, retail pharmacies and online pharmacies) across seven major regions (North America, Latin America, Europe, East Asia, South Asia, Oceania and Middle East & Africa). Request For No-Obligation Table Of Content Explore Fact.MR’s Coverage on the Healthcare Domain Movement Disorder Market: Growing prevalence of the neurological diseases is expected to contribute towards growth of the global movement disorder market. As manufacturers are increasingly focusing on development and innovation of products, growth of the global market is expected to remain positive. This Fact.MR report analyzes the expansion of global movement disorder market till date, and provides key insights on the growth of the market for the forthcoming decade. Epistaxis Market: The scope of Fact.MR’s report is to analyze the global epistaxis market and provide readers an unbiased and accurate analysis. Medical device manufacturers, research institutes, and raw material suppliers in the global epistaxis market can benefit from the analysis offered in this report. This report offers a comprehensive analysis, which can be of interest to leading trade magazines and medical journals pertaining to epistaxis. Spine Devices Market: Explore Fact.MR’s insightful coverage on the global spine devices market, mapping all the key trends, opportunities and drivers anticipated to influence growth trajectory for the upcoming decade. A detailed competitive analysis further enhances the reliability of this study. 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IgorGolovniov/Shutterstock Although January was a fairly slow month for PDUFA dates for the U.S. Food and Drug Administration, February has a stronger schedule. Igor Golovniov / Shutterstock Although January was a fairly slow month for PDUFA dates for the U.S. Food and Drug Administration (FDA), February has a stronger schedule. Of course, given today’s stories, it appears the agency was using their open January schedule to get a head start on February’s approvals. Alnylam’s Givorsiran for Acute Hepatic Porphyria Cambridge, Massachusetts-based Alnylam Pharmaceuticals had a target action date of February 4 for its New Drug Application (NDA) for givosiran for acute hepatic porphyria (AHP). The FDA approved the drug on November 20, 2019 under the trade name Givlaari. Givosiran is an investigational RNA therapy that targets aminolevulinic acid synthase 1 (ALAS1). The NDA was granted Priority Review. “We believe the approval of Givlaari represents a landmark event for the advancement of precision genetic medicines, providing new hope for patients and their caregivers living with the debilitating manifestations of AHP and unpredictable nature of AHP attacks, as well as for the doctors who diagnose and treat these patients,” said John Maraganore, Alnylam’s chief executive officer. “We are grateful to the investigators, patients and families who have helped make this new treatment option a reality for the AHP community.” AHP is a family of rare, genetic diseases marked by life-threatening attacks for for some patients, chronic debilitating symptoms. There are four subtypes, each caused by a genetic defect that causes enzyme deficiencies in the heme biosynthesis pathway in the liver. They are acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP) and ALAD-deficiency porphyria (ADP). The accumulation of neurotoxic heme intermediates aminolevulinic acid (ALA) and porphobilinogen (PBG) is believed to be responsible for the attacks and ongoing symptoms. The symptoms include severe, diffuse abdominal pain, weakness, nausea, and fatigue. RNAi is a natural cellular process of gene silencing. On January 31, 2020, the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval for Givlaari for AHP. Blueprint Medicines’s Avapritinib for Gastrointestinal Stromal Tumors Blueprint Medicines , also headquartered in Cambridge, Massachusetts, had a target action date of February 14 for its NDA for avapritinib for adults with PDGFRA Exon 18 mutant gastrointestinal stromal tumors (GIST), regardless of previous therapy, and fourth-line GIST. It was also under Priority Review. It was also granted Breakthrough Therapy Designation for patients with unresectable or metastatic GIST harboring the PDGFRalpha D842V mutation. On January 9, 2020, the FDA approved the drug under the trade name Ayvakit. Avapritinib is a highly selective KIT and PDGFRA inhibitor. It is initially being developed for advanced GIST, advanced systemic mastocytosis (SM), and indolent and smoldering SM. GIST is a sarcoma, a tumor of bone or connective tissue, of the GI tract. These types of tumors originate in cells in the wall of the GI tract and occur most often in the stomach or small intestine. Typically, patients are diagnosed between the ages of 50 and 80, usually triggered by GI bleeding. The drug was approved on the basis of data from the Phase I NAVIGATOR clinical trial. “Today’s approval of Ayvakit brings forward a new standard of care for patients with PDGFRA exon 18 mutant GIST, a genomically defined population that previously had very limited treatment options,” said Michael Heinrich, professor of Medicine at Oregon Health & Science University and an investigator on the NAVIGATOR trial. “For the first time, we can offer these patients a highly effective treatment that targets the underlying genetic cause of their disease.” He went on to say, “Building on our growing understanding of the molecular basis of GIST, this milestone ushers in a new era of precision medicine in this disease. The FDA approval represents a call to action to conduct mutational testing in all patients with GIST before initiating kinase inhibitor therapy, as recommended by clinical guidelines, so appropriate patients may realize the benefits of this promising new medicine.”