Alnylam Receives Positive Reimbursement Recommendation from the Canadian Agencies for Drugs and Technology in Health (CADTH) for use of GIVLAARI® for the Treatment of Acute Hepatic Porphyria (AHP) in Adults

-- 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. 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 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.