Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Inclisiran in Children (2 to Less Than 12 Years) With Homozygous Familial Hypercholesterolemia and Elevated LDL-cholesterol

This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 2 to <12 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDLC).

Start Date31 Mar 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

NCT06597019 / RecruitingPhase 3

Two Part (Double-blind Inclisiran Versus Placebo [Year 1] Followed by Open-label Inclisiran [Year 2]) Randomized Multicenter Study to Evaluate Safety, Tolerability and Efficacy of Inclisiran in Children (6 to Less Than 12 Years) With Heterozygous Familial Hypercholesterolemia and Elevated LDL- Cholesterol

This is a pivotal phase III study designed to evaluate safety, tolerability, and efficacy of inclisiran in children (aged 6 to <12 years) with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDLC).

Start Date09 Dec 2024

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

NCT06501443 / Not yet recruitingPhase 4

Latin America Lipid Optimization After Acute Event in Patients With AthErosclerotic CardiovasculaR DiseaSe and High LDL-C

This is an open label, patient-level 1:1 randomized clinical trial in a multi-country study aiming to evaluate the real-world impact of inclisiran + Usual Care (UC) vs UC alone on LDL-C lowering, patient-reported outcomes, and healthcare resource utilization in an in-hospital population of patients, admitted during the acute setting, stabilized and before discharge, following an acute cardiovascular event.

Start Date29 Nov 2024

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

100 Clinical Results associated with Inclisiran sodium

100 Translational Medicine associated with Inclisiran sodium

100 Patents (Medical) associated with Inclisiran sodium

190

Literatures (Medical) associated with Inclisiran sodium

01 Jan 2025·INTERNATIONAL JOURNAL OF CARDIOLOGY

Clinical reality and challenges with familial hypercholesterolemia patients' management. 2024 results from the Regional Center for Rare Diseases (RCRD) Registry in Poland

Article

Author: Rutkowska, Lena ; Lewek, Joanna ; Mierczak, Karina ; Bielecka-Dąbrowa, Agata ; Adach, Weronika ; Konopka, Agnieszka ; Gach, Agnieszka ; Starostecka, Ewa ; Banach, Maciej ; Sosnowska, Bożena

BACKGROUND:

Despite advancements in early diagnosis and effective medications in last decade, most heterozygous familial hypercholesterolemia (heFH) patients still fail to achieve their low-density lipoprotein cholesterol (LDL-C) goals and remain at residual cardiovascular disease risk. We present recent data from the regional FH registry in Poland, highlighting the challenges and real-life clinical management of FH patients.

METHODS:

The registry is held at the Regional Centre for Rare Diseases, founded in 2016, at the 2nd largest, supraregional hospital in Poland, where >80 different rare diseases in patients from all over Poland are diagnosed and treated, including phenotypically or genetically diagnosed FH patients. Our analysis focused on both children and adult FH patients, excluding those treated with inclisiran due to a small sample size (n = 5).

RESULTS:

We studied 173 consecutive heFH patients, median age for adult population was 40 years (range: 27-57), of whom 56.14 % were women. Among the population, 82.1 % were adults (n = 142), and 31 were children (17.92 %; median age 9 (8-13), females 58.16 %). Children exhibited lower total cholesterol and triglyceride levels compared to adults, with no significant differences in LDL-C and high-density lipoprotein cholesterol (HDL-C) levels. Molecular diagnosis in the whole population revealed that 76.6 % had an LDL receptor (LDLR) mutation, while 23.4 % had an apolipoprotein B (APOB) mutation. Risk assessment categorized patients into high (70.7 %), very high (22.1 %), and extremely high (7.1 %) risk groups. Triple therapy achieved treatment goals in 61.76 % of adults and 70.97 % of children. At baseline, 36.62 % of adult patients were not using statins. High-intensity statin therapy combined with ezetimibe was initiated for the remaining patients. Only 3.33 % of patients avoided statins due to complete intolerance. Ezetimibe was used in 57.27 % of patients (mostly in combination therapy), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were prescribed for 28.17 % FH patients. In adults receiving statin and ezetimibe therapy, median achieved LDL-C was 141 mg/dl (107-184). For triple therapy, median achieved LDL-C was 52.5 mg/dL (32-86.5). Overall median achieved LDL-C in the study population was 99.5 mg/dl (57.5-145.4). PCSK9 inhibitors reduced LDL-C by 165.6 mg/dl. Combination therapy did not significantly alter baseline lipoprotein(a) (Lp(a)) levels (p = 0.134), and PCSK9 inhibitors led to a mean Lp(a) reduction of 18.66 mg/dl (45 % reduction; p = 0.013). Multivariable regression analysis identified key factors for achieving LDL-C targets in FH patients: DLCN total score, DLCN category, ezetimibe use, and PCSK9 inhibitors.

CONCLUSIONS:

In Poland, FH patients are often diagnosed too late (usually over 40 years of age), and many still do not reach their LDL-C goals. Combination LLT double or triple therapy significantly increases the likelihood of achieving LDL-C targets - even up to fivefold. Therefore, unrestricted access to PCSK9 inhibitors for all FH patients is crucial, without the current limitations imposed by drug reimbursement programs like B101.

01 Dec 2024·Atherosclerosis plus

Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials

Review

Author: Dongare, Shirish ; Jawla, Shantanu ; Kamboj, Geetank ; Barman, Parinita ; Iannuzzo, Gabriella

Background and aims:

Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk.

Methods:

EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs.

Results:

The search strategy yielded 2104 citations. Post screening for eligibility, nine unique trials/studies (84 publications) were identified. Among these, one trial each was identified for bempedoic acid and alirocumab, three for evolocumab, and four for ezetimibe. No published literature documenting the cardiovascular outcomes of inclisiran was identified. Only one trial (CLEAR Outcomes) included statin-intolerant patients at baseline. Most studies evaluated a 3-component, 4-component, or 5-component major adverse cardiovascular events composite as an outcome along with individual components. The quality of the included trials was found to be fair-to-good.

Conclusions:

The systematic review findings emphasise the significance of considering non-statin LLTs as viable treatment options for individuals with CVD or high cardiovascular risk who cannot tolerate or achieve optimal lipid control with statin therapy alone.

22 Oct 2024·ANALYTICAL CHEMISTRY

An Accurate and Fast ³¹P qNMR Assay Method for Oligonucleotide Therapeutics

Article

Author: Li, Jiayi ; Chen, Kang ; Chen, Fu ; Kozak, Darby ; Wang, Yan ; Zhang, Deyi

Chemically modified nucleic acid molecules have been developed as oligonucleotide therapeutics, and its assay is critical in quality assurance. The common DNA/RNA quantification method using UV-260 nm can lack accuracy because of structure modifications and the possible formation of higher-order structure (HOS). Additionally, process-associated water and counterions affect the accuracy in gravimetric analysis. Thus, to improve accuracy, efficiency, and flexibility, in this work a fast (<1 h) externally referenced ³¹P quantitative-NMR (qNMR) method was developed. The qNMR assay results agreed within 1-5% of the UV-260 nm results for the single-stranded DNA standards, confirming the method accuracy. Next, an NMR and UV comparison study was performed on intact oligonucleotide drug products. The ³¹P qNMR method showed 7 ± 2%, 8 ± 1%, and 12 ± 1% lower concentration values compared with drug product labels for eteplirsen, inotersen, and inclisiran, respectively. Meanwhile the UV-260 nm results showed 28 ± 3%, 10 ± 3%, and 10 ± 1% lower concentrations than the label for the same three drugs. The agreement between NMR and UV for phosphorothioate (PS)-based inotersen and mostly phosphodiester (PO)-based inclisiran suggest that the labeled concentration may have been obtained using different extinction coefficients. The underestimate of UV results for eteplirsen, which has a phosphorodiamidate morpholino oligomer (PMO) structure, suggests that the UV-260 nm extinction coefficient may need to be re-established for the PMO based oligonucleotide. Therefore, the ³¹P qNMR method could be a primary assay method for the oligonucleotide drug and reference standard.

192

News (Medical) associated with Inclisiran sodium

10 Dec 2024

·www.globenewswire.com

CAMP4 Appoints John Maraganore and Rachel Meyers as Strategic Advisors

Industry veterans John Maraganore, Ph.D., and Rachel Meyers, Ph.D., to provide strategic guidance on the company’s RNA Actuating platform to develop a new class of RNA medicines that upregulate protein coding genesCAMBRIDGE, Mass., Dec. 10, 2024 (GLOBE NEWSWIRE) -- CAMP4 Therapeutics Corporation (“CAMP4”) (Nasdaq: CAMP), a clinical-stage biotechnology company developing a pipeline of regRNA-targeting therapeutics designed to upregulate gene expression with the goal of restoring healthy protein levels across a range of genetic diseases, today announced the appointments of John Maraganore, Ph.D., and Rachel Meyers, Ph.D., as strategic advisors to the Company. For nearly 20 years, Dr. Maraganore served as the founding Chief Executive Officer and Director of Alnylam where he led the company’s programs in RNA interference through global commercialization, resulting in the launch of the first four RNAi therapeutics, ONPATTRO®, GIVLAARI®, OXLUMO®, and LEQVIO®. Additionally, Dr. Meyers brings more than two decades of life sciences leadership, research, and development experience in RNA-based medicines, having spent nearly 14 years at Alnylam where she most recently served as Senior Vice President of Research and RNAi Lead Development. She currently sits on the company’s Scientific Advisory Board. “We feel privileged and are delighted to welcome Drs. Maraganore and Meyers to our CAMP4 team as strategic advisors,” said Josh Mandel-Brehm, Chief Executive Officer of CAMP4. “We view their joining the team as a testament to the promise and potential of our approach for upregulating gene expression to potentially address a broad range of diseases. As we prepare for 2025, we look forward to benefiting from their insights and expertise as we advance our efforts in bringing potentially transformative RNA medicines to patients in need of disease-modifying solutions.” Dr. Maraganore added, “The targeted upregulation of gene expression has been a long-standing challenge for the field, and by applying established and clinically validated antisense oligonucleotide technology to groundbreaking science, CAMP4 could potentially make a meaningful impact on patients across a broad range of diseases. I look forward to working with them as they pioneer the field of upregulation.” Prior to his role at Alnylam, Dr. Maraganore led the product franchises in oncology, cardiovascular, inflammatory, and metabolic diseases for Millennium Pharmaceuticals, in addition to leadership of M&A, strategy, and biotherapeutics. Earlier in his career, Dr. Maraganore invented and spearheaded the development of ANGIOMAX® (bivalirudin) for injection while at Biogen and was also a scientist at ZymoGenetics, Inc., and the Upjohn Company. He currently serves as a Venture Partner at ARCH Venture Partners, a Venture Advisor at Atlas Ventures, an Executive Partner at RTW Investments, a Senior Advisor for Blackstone Life Sciences, and a Senior Advisor for Jeffries Financial Group. Beyond his leadership roles in the investment community, Dr. Maraganore also sits on the Board of Directors for multiple publicly traded companies, including Beam Therapeutics, Kymera Therapeutics, Rapport Therapeutics, and Takeda Pharmaceuticals. He received his B.A., M.S., and Ph.D. in biochemistry and molecular biology at the University of Chicago. Dr. Meyers currently serves as a member of the Board of Directors of Korro Bio (Nasdaq: KRRO), a biopharmaceutical company focused on discovering, developing, and commercializing a new class of genetic medicines based on editing RNA, and also holds a variety of advisory roles within the biotech community. Most recently, she served as Founder and Chief Scientific Officer at Faze Medicines, a Third Rock Ventures-spawned biotech company focused on treating diseases of high unmet need through the perturbation of biomolecular condensates. Earlier in her career, Dr. Meyers was a senior scientist at Millennium Pharmaceuticals and today serves on multiple scientific advisory boards, including the National Advisory Board on Innovation and Entrepreneurship through the Department of Commerce. Furthermore, she is listed as an inventor on numerous patents and patent applications and has authored many peer-reviewed publications. Dr. Meyers received her postdoctoral training with Lew Cantley at Harvard Medical School in signal transduction and earned her Ph.D. in biology from Nobel laureate Phil Sharp at the Massachusetts Institute of Technology in in vitro transcription. She earned her BA in Biochemistry from Brandeis University. “I’ve had the unique opportunity to work alongside tremendously talented professionals who have led the shaping of the RNA medicines space,” said Dr. Meyers. “Having been at the forefront of these scientific breakthroughs, I believe now more than ever RNA-based therapies are poised to continue transforming how we treat patients with complex diseases. Having the opportunity to advise CAMP4 as they continue advancing the field is an extension of the work to which I’ve committed my career.” About CAMP4 Therapeutics CAMP4 is developing disease-modifying treatments for a broad range of genetic diseases where amplifying healthy protein may offer therapeutic benefits. Our approach amplifies mRNA by harnessing a fundamental mechanism of how genes are controlled. To amplify mRNA, our therapeutic ASO drug candidates target regRNAs, which act locally on transcription factors and are the master regulators of gene expression. CAMP4’s proprietary RAP Platform™ enables the mapping of regRNAs and generation of therapeutic candidates designed to target the regRNAs associated with genes underlying haploinsufficient and recessive partial loss-of-function disorders, of which there are more than 1,200, in which a modest increase in protein expression may have the potential to be clinically meaningful. Learn more about us at www.CAMP4tx.com and follow us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements which involve risks, uncertainties and contingencies, many of which are beyond the control of the Company, which may cause actual results, performance, or achievements to differ materially from anticipated results, performance, or achievements. All statements other than statements of historical facts contained in this press release are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements concerning CAMP4’s plans, objectives, expectations and intentions; the timing and results of ongoing and future clinical trials, including expectations on the timing of reporting SAD and MAD data from and seeking regulatory approval for the CMP-CPS-001 trial; its growth strategy; and cash balance guidance. The forward-looking statements in this press release speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions that could cause the Company’s actual results to differ materially from those anticipated in the forward-looking statements, including, but not limited to: the Company’s limited operating history, incurrence of substantial losses since the Company’s inception and anticipation of incurring substantial and increasing losses for the foreseeable future; the Company’s need for substantial additional financing to achieve the Company’s goals; the uncertainty of clinical development, which is lengthy and expensive, and characterized by uncertain outcomes, and risks related to additional costs or delays in completing, or failing to complete, the development and commercialization of the Company’s current product candidates or any future product candidates; delays or difficulties in the enrollment and dosing of patients in clinical trials; the impact of any significant adverse events or undesirable side effects caused by the Company’s product candidates; potential competition, including from large and specialty pharmaceutical and biotechnology companies; the Company’s ability to realize the benefits of the Company’s current or future collaborations or licensing arrangements and ability to successfully consummate future partnerships; the Company’s ability to obtain regulatory approval to commercialize any product candidate in the United States or any other jurisdiction, and the risk that any such approval may be for a more narrow indication than the Company seeks; the Company’s dependence on the services of the Company’s senior management and other clinical and scientific personnel, and the Company’s ability to retain these individuals or recruit additional management or clinical and scientific personnel; the Company’s ability to grow the Company’s organization, and manage the Company’s growth and expansion of the Company’s operations; risks related to the manufacturing of the Company’s product candidates, which is complex, and the risk that the Company’s third-party manufacturers may encounter difficulties in production; the Company’s ability to obtain and maintain sufficient intellectual property protection for the Company’s product candidates or any future product candidates the Company may develop; the Company’s reliance on third parties to conduct the Company’s preclinical studies and clinical trials; the Company’s compliance with the Company’s obligations under the licenses granted to the Company by others, for the rights to develop and commercialize the Company’s product candidates; risks related to the operations of the Company’s suppliers; and other risks and uncertainties described in the section “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, as well as other information we file with the Securities and Exchange Commission. The forward-looking statements in this press release are inherently uncertain and are not guarantees of future events. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond the Company’s control, you should not unduly rely on these forward-looking statements. The events and circumstances reflected in the forward-looking statements may not be achieved or occur and actual future results, levels of activity, performance and events and circumstances could differ materially from those projected in the forward-looking statements. Moreover, the Company operates in an evolving environment. New risks and uncertainties may emerge from time to time, and management cannot predict all risks and uncertainties. Investors, potential investors, and others should give careful consideration to these risks and uncertainties. Except as required by applicable law, the Company does not undertake to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contacts Investor Relations:Sandya von der WeidLifeSci Advisorssvonderweid@lifesciadvisors.com Media:Jason Braco, Ph.D.LifeSci Communicationsjbraco@lifescicomms.com

Executive ChangeOligonucleotide

25 Nov 2024

·www.businesswire.com

Alnylam Announces U.S. Food and Drug Administration Acceptance of Supplemental New Drug Application for Vutrisiran for the Treatment of ATTR Amyloidosis with Cardiomyopathy

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Company’s supplemental New Drug Application (sNDA) for vutrisiran, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM). Based on the Company’s use of a Priority Review Voucher, the FDA has set an action date goal of March 23, 2025, under the Prescription Drug User Fee Act (PDUFA). The FDA has informed the Company that it is not planning to hold an advisory committee meeting at this time to review the application. Vutrisiran is the generic name for AMVUTTRA ® , which is currently approved by the FDA for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. By rapidly knocking down both mutant and wild‑type transthyretin (TTR), vutrisiran addresses the underlying cause of transthyretin amyloidosis (ATTR). If approved, vutrisiran would become the first therapeutic approved in the U.S. to treat both the polyneuropathy manifestations of hATTR and cardiomyopathy manifestations of ATTR amyloidosis. “We are pleased that the FDA has accepted our sNDA for vutrisiran for the treatment of ATTR with cardiomyopathy – a steadily progressing, debilitating and ultimately fatal disease,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “In HELIOS-B, treatment with vutrisiran improved cardiovascular outcomes, survival, disease progression and quality of life, as compared to placebo, in a population reflective of today’s patients on substantial background treatment. We look forward to working with the FDA to support their review of the application and bring vutrisiran to patients with ATTR-CM in the U.S. early next year.” The supplemental application to the FDA was based on positive results from HELIOS-B, a randomized, double-blind, placebo-controlled multicenter global Phase 3 study in patients with ATTR-CM. The study demonstrated favorable effects of vutrisiran on outcomes of death and cardiovascular events, functional capacity and quality of life in patients with ATTR-CM. These treatment effects were seen on top of substantial background standard of care treatments. Vutrisiran demonstrated encouraging safety and tolerability consistent with the established profile of the drug. Detailed results from the study were presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine on August 30, 2024. AMVUTTRA ® (vutrisiran) U.S. Indication and Important Safety Information Indication AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. Important Safety Information Reduced Serum Vitamin A Levels and Recommended Supplementation AMVUTTRA treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body. 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 common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%). For additional information about AMVUTTRA, please see the full U.S. Prescribing Information . About AMVUTTRA ® (vutrisiran) AMVUTTRA ® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of mutant and wild-type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, AMVUTTRA 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. For more information about AMVUTTRA, including the full U.S. Prescribing Information , visit AMVUTTRA.com . 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. 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 or disease pathway 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 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’s commercial RNAi therapeutic products are ONPATTRO® (patisiran), AMVUTTRA® (vutrisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. 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. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on X (formerly Twitter) at @Alnylam , or on LinkedIn , Facebook , or Instagram . Alnylam Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, Alnylam’s expectations regarding the safety and efficacy of vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy, including the safety, tolerability and favorable effects of vutrisiran on outcomes of death and cardiovascular events, functional capacity and quality of life in patients with ATTR-CM; whether the FDA will convene an advisory committee in connection with the FDA’s review of Alnylam’s supplemental application for approval of vutrisiran for the treatment of patients with ATTR-CM; the potential for vutrisiran to obtain FDA approval for the treatment of patients with ATTR-CM, and the anticipated timing of such FDA approval; and the potential for Alnylam to achieve its Alnylam P 5 x25 vision of becoming a leading biopharma company should be considered forward-looking statements. 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, risks and uncertainties relating to: Alnylam’s ability to successfully execute on its “ Alnylam P 5 x25 ” strategy; Alnylam’s ability to successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates, including vutrisiran; actions or advice of regulatory agencies and Alnylam’s ability to obtain regulatory approval for its product candidates, including vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; and any delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s 2023 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q and in its other SEC filings. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

Clinical ResultDrug ApprovalPhase 3NDAPriority Review

21 Nov 2024

·endpts.com

With yearslong reorganization behind it, Novartis increases its sales guidance

Novartis’ reorganization is paying off, CEO Vas Narasimhan told investors at an event Thursday in London. The company raised its sales guidance through 2028 and now expects to grow sales at a 6% annual rate, as opposed to its previous expected growth rate of 5%. That additional percentage point reflects about $2.5 billion in additional sales between 2023 and 2028, CFO Harry Kirsch said Thursday on a call with reporters. Narasimhan attributed the updated guidance in part to Novartis’ transformation into a “pure-play” company. It’s been roughly a year since the drugmaker completed a global restructuring that involved the spinout of Sandoz, its generics unit. Narasimhan said the “simplified” structure has allowed Novartis to focus on “the biggest opportunities that we have in the pipeline.” “It’s been a three-year journey to streamline this portfolio, to go from what was one of the largest portfolios — 155 projects — down to 94,” he said on the same call. Novartis also touted a “sharpened” commercial structure, saying it allows for greater investment in key brands. Novartis is increasing its peak sales estimates for five products: Cosentyx, Kisqali, Kesimpta, Pluvicto and Leqvio. “For 25 years, Novartis led the industry in the number of FDA approvals, but we’re never in the top quartile in the value of those approvals,” Narasimhan told reporters. “It’s been a major effort to streamline down to what we think are the most high-value assets, and what that’s allowed us to do is increase the amount of resources we have on each project.” While Novartis has cited its radioligand therapy Pluvicto as one of several “large, in-market growth drivers in the base business,” Narasimhan said uptake is behind where executives would like it to be. The company alleviated concerns around radiopharma shortages by bringing on more manufacturing capacity. The company predicted Pluvicto would generate $2 billion in peak sales globally under its initial indication, an advanced type of prostate cancer. However, Narasimhan said he would have liked to get there faster, attributing the lag to challenges at community oncology centers. The drug generated $980 million in sales last year. “We were very successful in the large academic medical centers and hospitals,” he said. “It’s taken much longer to get community oncologists in the United States to utilize Pluvicto at rates that we hoped.” Novartis has applied for a label expansion to bring Pluvicto into the pre-taxane setting for patients with metastatic castration-resistant prostate cancer, which would triple the amount of patients eligible to receive it. The company is expecting a decision next year. “At that point in time, we would expect the acceleration to continue,” Narasimhan said.

100 Deals associated with Inclisiran sodium

External Link

KEGG	Wiki	ATC	Drug Bank
-	Inclisiran sodium	C10AX	DB14901

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Hypercholesterolemia	JP	Novartis Pharma KK	25 Sep 2023
Dyslipidemias	CN	Novartis Pharma AG	22 Aug 2023
Dyslipidemias	CN	Novartis Europharm Ltd.	22 Aug 2023
Primary Hyperlipidemia	US	Novartis Pharmaceuticals Corp.	07 Jul 2023
Atherosclerosis	AU	Novartis Pharmaceuticals Australia Pty Ltd.	14 Sep 2021
Heterozygous familial hypercholesterolemia	CA	Novartis Pharmaceuticals Canada, Inc.	26 Jul 2021
Hyperlipoproteinemia Type II	CA	Novartis Pharmaceuticals Canada, Inc.	26 Jul 2021
Complex dyslipidemia	EU	Novartis Europharm Ltd.	09 Dec 2020
Complex dyslipidemia	IS	Novartis Europharm Ltd.	09 Dec 2020
Complex dyslipidemia	LI	Novartis Europharm Ltd.	09 Dec 2020
Complex dyslipidemia	NO	Novartis Europharm Ltd.	09 Dec 2020
Primary hypercholesterolemia	EU	Novartis Europharm Ltd.	09 Dec 2020
Primary hypercholesterolemia	IS	Novartis Europharm Ltd.	09 Dec 2020
Primary hypercholesterolemia	LI	Novartis Europharm Ltd.	09 Dec 2020
Primary hypercholesterolemia	NO	Novartis Europharm Ltd.	09 Dec 2020

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Coronary Artery Disease	Phase 3	US	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	CN	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	JP	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	AR	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	AU	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	BE	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	BR	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	CA	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	CL	Novartis Pharmaceuticals Corp.	08 Jul 2022
Coronary Artery Disease	Phase 3	FR	Novartis Pharmaceuticals Corp.	08 Jul 2022

Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESC2024	Not Applicable	-	-	Inclisiran	hcpyminijs(aowbajyiel) = scjeymjtvk rzcmbnybeq (apfjnmyjol ) View more	-	31 Aug 2024
ESC2024	Not Applicable	Atherosclerosis	-	Inclisiran first	yoqgzxdvpg(rkvwuvndnt) = xcxaltgrxv aqawdxfuep (ysgtxaoblf )	-	30 Aug 2024
				Usual care	yoqgzxdvpg(rkvwuvndnt) = mgygorhzfy aqawdxfuep (ysgtxaoblf )
ESC2024	Not Applicable	Cardiovascular Diseases \| Hyperlipidemias	-	Inclisiran treatment	ebnifafhpl(vwdpxbnyeq) = cznrsujhxv dcgbpwinex (ezhbzcvoaw ) View more	-	30 Aug 2024
				Placebo	ebnifafhpl(vwdpxbnyeq) = stnjnxdurl dcgbpwinex (ezhbzcvoaw )
ESC2024	Not Applicable	-	-	Inclisiran + Usual Care	iiivbwqemq(zndqnqzxpt) = Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs compared similarly between IF and UC for each subgroup (IF: 35.5−69.2%, UC: 34.2−84.2%, and IF: 3.2−16.9%, UC: 0.0−36.8%, respectively) jzyybcztpc (yfqigjybdt )	-	30 Aug 2024
ESC2024	Not Applicable	Plaque, Atherosclerotic	-	High-intensity statin + optional ezetimibe	lkkzjtowjw(jqoiirdbyy) = jkglrvlhag zodxsbjfza (nufnroletz )	-	30 Aug 2024
NCT05763875 (V-MONO, NEWS) Manual	Phase 3	Atherosclerosis	-	Leqvio	fgbjbufjfd(elbahzfngi) = met its primary endpoints. mlydpxjbec (sliuivicdg ) Met	Positive	28 Aug 2024
				Ezetimibe
ENDO2024	Not Applicable	LDL-C levels	69	Inclisiran	xjumrhalsb(kuxbvixrdr) = Only one subject discontinued Inclisiran due to experiencing a generalized rash qntkwawpld (tqtwkgvbcq )	Positive	01 Jun 2024
				Statins, Ezetimibe, Bempedoic Acid, PCSK-9 inhibitors
NCT03814187 (ORION-8, Pubmed)	Phase 2/3	Homozygous familial hypercholesterolemia \| Atherosclerosis \| Heterozygous familial hypercholesterolemia	3,274	Inclisiran	azxcdjqqxv(xhkieihota) = 5.9% of inclisiran-treated patients olfrbrllla (urxhaldouq )	Positive	16 May 2024
NCT04929249 (V- INITIATE, PRNewswire) Manual	Phase 3	Atherosclerosis	450	Leqvio	ummjvawsqj(zdnsjeewtl) = dfopdtgudk ctxqftjbez (rqiplzhdgd ) View more	Positive	06 Apr 2024
NCT04807400 (SPIRIT, CTgov)	Phase 3	Hyperlipoproteinemias \| Atherosclerosis	892	Background lipid lowering therapy+Inclisiran (Inclisiran)	mzgicetwwc(unlvcstwsj) = zojbkhqyzr sbtahtevdo (bgqabflzij, vakmzcjqup - cyoqgvrupb) View more	-	25 Mar 2024
				Behavioural Support+Inclisiran (Inclisiran + BS)	mzgicetwwc(unlvcstwsj) = wnerrffiqw sbtahtevdo (bgqabflzij, rugapdkxgv - aybrlcvucj) View more

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