Cutaneous Mastocytosis

− Type II Variation Submission Based on the Positive HELIOS-B Phase 3 Study in which Vutrisiran Significantly Reduced the Risk of Death and Cardiovascular Events Relative to Placebo – CAMBRIDGE, MA, USA I October 16, 2024 I Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNA interference (RNAi) therapeutics company, today announced the submission of a Type II Variation to the European Medicines Agency (EMA) for vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). Vutrisiran is the generic name for AMVUTTRA ® , which is currently approved in the European Union (EU) for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy. “Today marks another important milestone in our journey to bring RNAi therapeutics to patients with high unmet need around the world,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “ATTR-CM is a rapidly progressive, debilitating, and life-threatening disease that is an increasingly recognized cause of heart failure. Vutrisiran rapidly knocks down TTR, and in the HELIOS-B study treatment with vutrisiran substantially reduced all-cause mortality and cardiovascular events, underscoring the potential of this therapy for those living with the disease. We look forward to working closely with the EMA with the aim to bring this new treatment option to patients as soon as possible.” The regulatory application is based on positive results from the pivotal HELIOS-B Phase 3, randomized, double-blind, placebo-controlled multicenter global study which met all 10 of its primary and secondary endpoints across both the overall and monotherapy populations, each with statistical significance. The findings demonstrated the effects of vutrisiran on outcomes of mortality and cardiovascular events, as well as functional capacity (6-minute walk test), quality of life (Kansas City Cardiomyopathy Questionnaire), and heart failure symptoms and severity (NYHA class) in patients with ATTR-CM. The safety profile of vutrisiran in HELIOS-B was consistent with the established profile of the drug for hATTR amyloidosis in adult patients with polyneuropathy. In HELIOS-B, rates of adverse events (AEs), serious AEs, severe AEs and AEs leading to study drug discontinuation were similar between the vutrisiran and placebo arms. Detailed results from the HELIOS-B study were published in The New England Journal of Medicine . A supplemental New Drug Application (sNDA) for vutrisiran has been submitted to the U.S. Food and Drug Administration (FDA) for the treatment of ATTR-CM. Additional regulatory submissions are planned globally. AMVUTTRA ® (vutrisiran) INDICATION AND IMPORTANT SAFETY INFORMATION Indication In Europe and the UK, vutrisiran is indicated for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy. Important Safety Information Reduced Serum Vitamin A Levels and Recommended Supplementation Vutrisiran treatment leads to a decrease in serum vitamin A levels. Supplementation of approximately, but not exceeding, 2500 IU to 3000 IU vitamin A per day is advised for patients taking vutrisiran. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness). Adverse Reactions The most frequently occurring adverse reactions in patients treated with vutrisiran were pain in extremity and arthralgia. Other commonly reported adverse reactions with vutrisiran were dyspnoea, injection site reaction and increase in blood alkaline phosphatase. For additional information about vutrisiran, please see the full Summary of Product Characteristics . About AMVUTTRA ® (vutrisiran) AMVUTTRA ® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of variant and wild‑type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, vutrisiran is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Vutrisiran is also in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), which encompasses both wild-type and hereditary forms of the disease. About ATTR Transthyretin amyloidosis (ATTR) is an underdiagnosed, rapidly progressive, debilitating and fatal disease caused by misfolded transthyretin (TTR) proteins, which accumulate as amyloid deposits in various parts of the body, including the nerves, heart and gastrointestinal tract. Patients may present with polyneuropathy, cardiomyopathy or both manifestations of disease. There are two different forms of ATTR – hereditary ATTR (hATTR), which is caused by a TTR gene variant and affects approximately 50,000 people worldwide, and wild-type ATTR (wtATTR), which occurs without a TTR gene variant and impacts an estimated 200,000-300,000 people worldwide. 1-4 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. 5 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. 6 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 or disease pathway proteins – thus preventing them from being made. 5 This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases. About Alnylam Pharmaceuticals Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “ Alnylam P 5 x25 ” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. 1 Hawkins PN, Ando Y, Dispenzeri A, et al. Ann Med . 2015;47(8):625-638. 2 Gertz MA. Am J Manag Care . 2017;23(7):S107-S112. 3 Conceicao I, Gonzalez-Duarte A, Obici L, et al. J Peripher Nerv Syst . 2016;21:5-9. 4 Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis . 2013;8:31. 5 Elbashir SM, Harborth J, Lendeckel W, et al. Nature . 2001;411(6836):494-498. 6 Zamore P. Cell . 2006;127(5):1083-1086. SOURCE: Alnylam Pharmaceuticals

New data to be presented will include biomarkers of disease progression and functional capacity from the ongoing Phase 1 study of nex-z, an investigational in vivo CRISPR gene editing therapy for ATTR amyloidosis CAMBRIDGE, Mass., Oct. 01, 2024 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today announced that interim data from the ongoing Phase 1 study of nexiguran ziclumeran (nex-z, also known as NTLA-2001) will be presented in a late-breaking oral presentation at the 2024 American Heart Association (AHA) Scientific Sessions, taking place November 16 – 18 in Chicago, Illinois. Nex-z is an investigational in vivo CRISPR-based gene editing therapy designed to be a single-dose treatment for transthyretin (ATTR) amyloidosis. Intellia leads development and commercialization of nex-z as part of a multi-target discovery, development and commercialization collaboration with Regeneron. The presentation will include safety, reduction in serum TTR and biomarkers of disease progression, and functional capacity data in patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM). Presentation Details Title: Nexiguran ziclumeran (nex-z, also known as NTLA-2001), an investigational in vivo CRISPR-based therapy for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM): interim report of the Phase 1 study Session: Late-Breaking Science 1: Celebrating a Century of Cardiovascular Science: From Prevention to Treatment, to Cure Session Type: Late-Breaking Science Date and Time: Saturday, November 16, 2024, from 8:30-9:45 a.m. CST Presenter: Marianna Fontana, M.D., Ph.D., Professor of Cardiology and Honorary Consultant Cardiologist, University College London Centre for Amyloidosis, London, UK Location: Main Event I About nexiguran ziclumeran (nex-z, also known as NTLA-2001)Based on Nobel Prize-winning CRISPR/Cas9 technology, nex-z has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis. Nex-z is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein. Nex-z is the first investigational CRISPR therapy to be administered systemically to edit genes inside the human body. Interim Phase 1 clinical data showed the administration of nex-z led to consistent, deep and long-lasting TTR reduction. Intellia leads development and commercialization of nex-z as part of a multi-target discovery, development and commercialization collaboration with Regeneron. About Transthyretin (ATTR) AmyloidosisTransthyretin amyloidosis, or ATTR amyloidosis, is a rare, progressive and fatal disease. Hereditary ATTR (ATTRv) amyloidosis occurs when a person is born with mutations in the TTR gene, which causes the liver to produce structurally abnormal transthyretin (TTR) protein with a propensity to misfold. These damaged proteins build up as amyloid in the body, causing serious complications in multiple tissues, including the heart, nerves and digestive system. ATTRv amyloidosis predominantly manifests as polyneuropathy (ATTRv-PN), which can lead to nerve damage, or cardiomyopathy (ATTRv-CM), which can lead to heart failure. Some individuals without the genetic mutation produce non-mutated, or wild-type TTR proteins that become unstable over time, misfolding and aggregating in disease-causing amyloid deposits. This condition, called wild-type ATTR (ATTRwt) amyloidosis, primarily affects the heart. There are an estimated 50,000 people worldwide living with ATTRv amyloidosis and between 200,000 and 500,000 people with ATTRwt amyloidosis. There is no known cure for ATTR amyloidosis and currently available medications are limited to slowing accumulation of misfolded TTR protein. About Intellia TherapeuticsIntellia Therapeutics, Inc. (NASDAQ:NTLA) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. The company’s in vivo programs use CRISPR to enable precise editing of disease-causing genes directly inside the human body. Intellia’s ex vivo programs use CRISPR to engineer human cells outside the body for the treatment of cancer and autoimmune diseases. Intellia’s deep scientific, technical and clinical development experience, along with its people, is helping set the standard for a new class of medicine. To harness the full potential of gene editing, Intellia continues to expand the capabilities of its CRISPR-based platform with novel editing and delivery technologies. Learn more at intelliatx.com and follow us @intelliatx. Forward-Looking Statements This press release contains “forward-looking statements” of Intellia Therapeutics, Inc. (“Intellia” or the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellia’s beliefs and expectations regarding: the safety, efficacy, success and advancement of its clinical program for nexiguran ziclumeran (“nex-z”, also known as “NTLA-2001”) for transthyretin (“ATTR”) amyloidosis pursuant to its clinical trial applications and investigational new drug submission, including its potential to become the first one-time treatment for ATTR amyloidosis; and the expected timing of data releases, including the oral presentation planned for November 16 at the 2024 American Heart Association (AHA) Scientific Sessions. Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellia’s ability to protect and maintain its intellectual property position; risks related to Intellia’s relationship with third parties, including its licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; uncertainties related to the authorization, initiation, enrollment and conduct of studies and other development requirements for its product candidates, including nex-z; the risk that any one or more of Intellia’s product candidates, including nex-z, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies, such as the Phase 1 clinical study of nex-z, will not be predictive of future results in connection with future studies for the same product candidate or Intellia’s other product candidates; and risks related to Intellia’s reliance on collaborations, including that its collaboration with Regeneron will not continue or will not be successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellia’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Intellia’s most recent annual report on Form 10-K and quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in Intellia’s other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law. Intellia Contacts: Investors:Ian KarpSenior Vice President, Investor Relations and Corporate Communicationsian.karp@intelliatx.com Lina LiSenior Director, Investor Relations and Corporate Communicationslina.li@intelliatx.com Media:Matt CrensonTen Bridge Communicationsmedia@intelliatx.com mcrenson@tenbridgecommunications.com This press release was published by a CLEAR® Verified individual.

WEDNESDAY, Sept. 18, 2024 -- Monthly use of erenumab injections (140 mg) is safe and effective in achieving medication overuse headache (MOH) remission in patients with nonopioid chronic migraine (CM) and MOH, according to a study published online Sept. 16 in JAMA Neurology . Stewart J. Tepper, M.D., from the New England Institute for Neurology and Headache in Stamford, Connecticut, and colleagues assessed the safety and efficacy of erenumab in patients with nonopioid CM-MOH. The analysis included 584 participants randomly assigned to erenumab (70 mg or 140 mg) or placebo, once monthly for 24 weeks. The researchers found that at month 6, 69.1 percent of participants in the erenumab 140-mg group (odds ratio, 2.01; 95 percent confidence interval, 1.33 to 3.05; P < 0.001 versus placebo) and 60.3 percent in the erenumab 70-mg group (odds ratio, 1.37; 95 percent confidence interval, 0.92 to 2.05; P = 0.13 versus placebo) achieved MOH remission versus 52.6 percent of participants in the placebo group. From baseline, least squares mean change in average monthly acute headache medication days was –9.4 days in the erenumab 140-mg group (difference from placebo, –2.7) and –7.8 days in the erenumab 70-mg group (difference from placebo, –1.2). Throughout the treatment period, MOH remission was sustained in 61.3 percent of participants in the erenumab 140-mg group, 49.5 percent of participants in the 70-mg group, and 37.6 percent in the placebo group. The safety profile was similar to that seen in previous trials, with treatment-emergent adverse event incidence in the combined erenumab group of 66.8 percent, including most commonly constipation (15.2 percent) and COVID-19 (13.9 percent). "This study is the first controlled trial to provide American Academy of Neurology class I evidence of beneficial effects of a migraine preventive treatment in patients with CM-MOH (nonopioid)," the authors write. Several authors disclosed ties to pharmaceutical companies, including Amgen, which manufactures erenumab and funded the study. Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.