To evaluate the efficacy and safety of patisiran in patients with wtATTR amyloidosis and symptomatic polyneuropathy by evaluating the effect on neurologic impairment and quality of life.

Start Date03 Aug 2022

Sponsor / Collaborator

Alnylam Pharmaceuticals, Inc.

NCT04201418 / CompletedNot Applicable

A Phase 4 Multicenter Observational Study to Evaluate the Effectiveness of Patisiran in Patients With Polyneuropathy of Hereditary Transthyretin-Mediated (ATTRv) Amyloidosis With a V122I or T60A Mutation

To evaluate the effectiveness of patisiran in patients with ATTRv amyloidosis with polyneuropathy who have a V122I or T60A mutation.

Start Date18 Dec 2019

Sponsor / Collaborator

Alnylam Pharmaceuticals, Inc.

NCT03997383 / Active, not recruitingPhase 3

APOLLO-B: A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Patisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)

The purpose of this study is to evaluate the efficacy and safety of patisiran in participants with ATTR amyloidosis with cardiomyopathy.

Start Date04 Sep 2019

Sponsor / Collaborator

Alnylam Pharmaceuticals, Inc.

100 Clinical Results associated with Patisiran sodium

100 Translational Medicine associated with Patisiran sodium

100 Patents (Medical) associated with Patisiran sodium

226

Literatures (Medical) associated with Patisiran sodium

01 Jan 2025·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Analyte and probe melting temperature guided method development strategy for hybridization LC-MS/MS quantification of siRNAs

Article

Author: Lu, Angela ; Song, Zifeng ; Yuan, Long

Small interfering RNA (siRNA) is a novel class of double-stranded oligonucleotide therapeutics rapidly growing in drug research and development. Accurate, sensitive, and reliable quantification of siRNA analytes in biological samples is required to study their pharmacokinetics, toxicokinetics, and biodistribution. Hybridization LC-MS/MS can achieve highly sensitive and specific bioanalysis of single-stranded oligonucleotides, e.g., antisense oligonucleotides (ASOs); however, its application for bioanalysis of siRNA or other double-stranded oligonucleotides is limited. The detailed rationale and principles for assay development are still not well understood. In this work, we systematically evaluated key steps and parameters of hybridization LC-MS/MS assays, including probes (five different types compared), hybridization procedure and temperature, elution temperature, and column temperature using patisiran, an approved siRNA drug, as the test siRNA. Based on the evaluation, a practical and efficient melting temperature (Tm) guided strategy was developed for fast and reliable method development of hybridization LC-MS/MS assays for siRNA bioanalysis. The strategy was successfully applied to siRNA-A, a test siRNA, in mouse plasma over the range of 1.00-1000 ng/mL and the resulting method has been used to support multiple mouse studies. This method-development strategy showed great value as a general approach for other siRNAs or double-stranded oligonucleotides.

01 Jan 2025·EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

Optimization and evaluation of gastroresistant microparticles designed for siRNA oral delivery

Article

Author: Stalder, Thomas ; Moulari, Brice ; Koenig, Nathan ; Cornu, Raphaël ; Pellequer, Yann ; Laurent, Gautier ; Beduneau, Arnaud ; Martin, Hélène ; Jurin, Florian

Oral administration of siRNA is a challenging strategy for the local treatment of intestinal diseases, including cancer and inflammatory bowel disease. Both nucleic acids and delivery systems, especially lipid nanoparticles (LNPs), are sensitive to the acidic pH of the stomach, bile salts and digestive enzymes. The present work focuses on the design and evaluation of gastroresistant alginate microparticles (MPs) prepared with an original process for oral delivery of siRNA. MPs with a mean diameter of less than 200 µm were obtained without extrusion and emulsification methods. Onpattro® marketed pharmaceutical product and TNF-α siRNA-loaded LNPs were successfully microencapsulated with an efficiency of at least 80 %. Gastroresistance properties and intestinal release were demonstrated in simulated gastric and intestinal fluids. After exposure to simulated gastric fluid, MPs in contact with hepatocyte and LPS-activated monocyte-derived macrophage cell lines reduced the expression of transthyretin and TNF-α, demonstrating the preservation of the siRNA activity.

01 Dec 2024·ADVANCED DRUG DELIVERY REVIEWS

Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids

Review

Author: Brigger, Finn ; Bader, Johannes ; Leroux, Jean-Christophe

Extracellular vesicles (EVs) are increasingly investigated for delivering nucleic acid (NA) therapeutics, leveraging their natural role in transporting NA and protein-based cargo in cell-to-cell signaling. Their synthetic counterparts, lipid nanoparticles (LNPs), have been developed over the past decades as NA carriers, culminating in the approval of several marketed formulations such as patisiran/Onpattro® and the mRNA-1273/BNT162 COVID-19 vaccines. The success of LNPs has sparked efforts to develop innovative technologies to target extrahepatic organs, and to deliver novel therapeutic modalities, such as tools for in vivo gene editing. Fueled by the recent advancements in both fields, this review aims to provide a comprehensive overview of the basic characteristics of EV and LNP-based NA delivery systems, from EV biogenesis to structural properties of LNPs. It addresses the primary challenges encountered in utilizing these nanocarriers from a drug formulation and delivery perspective. Additionally, biodistribution profiles, in vitro and in vivo transfection outcomes, as well as their status in clinical trials are compared. Overall, this review provides insights into promising research avenues and potential dead ends for EV and LNP-based NA delivery systems.

205

News (Medical) associated with Patisiran 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

22 Nov 2024

·endpts.com

FDA approves BridgeBio's heart disease drug, setting up competition with Pfizer, Alnylam

The FDA approved BridgeBio’s acoramidis in a rare, genetic heart disease that’s expected to become an intense area of market competition, and a broad label will give it a near-immediate boost against the current leader. The drug, which will be branded as Attruby, is indicated to treat transthyretin amyloid cardiomyopathy (ATTR-CM), and its wholesale acquisition cost is $18,759.12 for a 28-day supply. Over the course of a year, that equates to about $244,500. Friday’s approval comes well ahead of the Nov. 29 decision date and about a month and a half after BridgeBio’s rival Alnylam filed an application with the FDA to expand the label for its drug, Amvuttra, to include ATTR-CM as well. (Its acceptance has not yet been announced, but Alnylam has said it intends to use a priority review voucher.) Both drugs had already received significant attention during clinical studies — and not all of it due to the trials’ data. BridgeBio CEO Neil Kumar caused a hullabaloo in July 2023 after posting a cryptic message on LinkedIn referring to Homer’s “The Odyssey,” and a claimed typo in an Alnylam presentation at a medical conference earlier this summer forced the company to update its slides — but not before its stock fell more than 8%. Notably, Attruby’s label said the drug reduces the likelihood of both hospitalization and death, a significant win for BridgeBio. Analysts were closely watching the labeling specifics, as the label for the first approved medicine to treat ATTR-CM — Pfizer’s tafamidis franchise (Vyndamax/Vyndaqel) — says it reduces hospitalization and mortality. “If you have this scenario where, for whatever reason, BridgeBio doesn’t end up with mortality in the indication statement, then odds are they’re at a commercial disadvantage,” Mizuho analyst Salim Syed told Endpoints News ahead of Friday’s decision. With Attruby approved and a potential Amvuttra decision in the first half of next year, the attention will turn to market dynamics. The drugs use different mechanisms of action, which may determine how they’re used. While Attruby and Vyndamax/Vyndaqel both aim to stabilize the misfolded proteins at the root of the disease, Amvuttra is designed to silence the gene causing misfolds through RNA interference. Analysts expect patients to opt for the stabilizers first, and then move to a silencer if they don’t respond well. Kumar said the same thing, telling Endpoints before the decision that “our first goal is really to make acoramidis the oral stabilizer of choice.” But most analysts anticipate Amvuttra will still be able to compete in the second-line setting. The total market is likely to surpass $10 billion, according to TD Cowen analyst Tyler Van Buren, with Vyndamax/Vyndaqel netting $3.9 billion in sales in the first nine months of 2024. Van Buren said Attruby sales could reach $2.5 billion annually by 2035. “There’s definitely upside to that number. That’s both US and ex-US [sales],” Van Buren said. Though ATTR-CM is a rare disease, its prevalence increased as doctors improved their tools to diagnose it, said Joshua Mitchell, a cardiologist at Washington University in St. Louis. Before Vyndamax/Vyndaqel’s approval in 2019, there were no drugs specifically approved to treat this condition, Mitchell said, and diagnoses were made through biopsies of the heart. But since then, “it’s been an explosion in the space,” he said. “We’ve really improved our ability to diagnose the disease, and it’s more common than we previously thought. And now we have competitors coming to the market, which is always fantastic, always good to have options.” Mitchell helped run one of BridgeBio’s trial sites and also recruited patients for a trial of another Alnylam drug, patisiran. The newer methods and drugs help patients feel better quickly, Mitchell added. Typically, ATTR-CM patients will feel healthy and normal, until all of a sudden they’re really sick, and the rapid onset can make patients feel blindsided. While the new drug approvals mark significant progress, there’s still more work to be done, Mitchell said. None of the stabilizers or silencers reverse the course of the disease, which is usually one of patients’ first questions after asking about safety profile. In its Phase 3 trial, more patients taking placebo experienced serious and severe treatment-related side effects. For now, though, Vyndamax/Vyndaqel, Attruby and Amvuttra will make up much of the near-term market. Kumar said that Attruby and other stabilizers and silencers should be able to prevent new deposition of the obstructive plaque associated with the disease. “What we’re trying to do is actually to intervene upstream, both with knockdowns and with small molecule stabilizers,” Kumar said. “So that’s one super-compelling frame to think about the history of these drug products.”

Drug ApprovalClinical ResultAcquisitionPhase 3Priority Review

100 Deals associated with Patisiran sodium

External Link

KEGG	Wiki	ATC	Drug Bank
D10794	Patisiran sodium	N07XX12	DB14582

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Amyloid Neuropathies, Familial	CA	Alnylam Netherlands BV	07 Jun 2019
Polyneuropathies	EU	Alnylam Netherlands BV	27 Aug 2018
Polyneuropathies	IS	Alnylam Netherlands BV	27 Aug 2018
Polyneuropathies	LI	Alnylam Netherlands BV	27 Aug 2018
Polyneuropathies	NO	Alnylam Netherlands BV	27 Aug 2018
Amyloidosis, Hereditary, Transthyretin-Related	US	Alnylam Pharmaceuticals, Inc.	10 Aug 2018

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Transthyretin Amyloid Cardiomyopathy	NDA/BLA	US	Alnylam Pharmaceuticals, Inc.	21 Feb 2023
Hematopoietic stem cell transplantation	NDA/BLA	US	Gamida Cell Ltd.	02 Jun 2022
Amyloid Neuropathies	Phase 3	US	Alnylam Pharmaceuticals, Inc.	01 Nov 2013
Amyloid Neuropathies	Phase 3	JP	Alnylam Pharmaceuticals, Inc.	01 Nov 2013
Amyloid Neuropathies	Phase 3	AR	Alnylam Pharmaceuticals, Inc.	01 Nov 2013
Amyloid Neuropathies	Phase 3	AU	Alnylam Pharmaceuticals, Inc.	01 Nov 2013
Amyloid Neuropathies	Phase 3	BR	Alnylam Pharmaceuticals, Inc.	01 Nov 2013
Amyloid Neuropathies	Phase 3	BG	Alnylam Pharmaceuticals, Inc.	01 Nov 2013
Amyloid Neuropathies	Phase 3	CA	Alnylam Pharmaceuticals, Inc.	01 Nov 2013
Amyloid Neuropathies	Phase 3	CY	Alnylam Pharmaceuticals, Inc.	01 Nov 2013

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02510261 (APOLLO, CTgov)	Phase 3	Amyloidosis, Hereditary, Transthyretin-Related	211	Patisiran (Prior Placebo Group of Study 004)	enpyghclax(qdyprepwsa) = sltgcrzvnc evimsmbwsj (jqlfgrggmz, wisaidxacb - vwvvvtvqoy) View more	-	06 Dec 2023
				Patisiran (Prior Patisiran Group of Study 004)	enpyghclax(qdyprepwsa) = srtcdckxrx evimsmbwsj (jqlfgrggmz, mdqpwbbfcp - uzhzbbvzpq) View more
ESC2023	Not Applicable	Transthyretin Amyloid Cardiomyopathy	-	Patisiran	mxwtczmavd(ktpxdkyqxi) = hbkvctghcb aeoydcipxl (xfdtsejhig )	-	25 Aug 2023
				Inotersen	tzqzmgozwj(mnggftlwxp) = exnkzhmlmm kbliboawub (rckzdjcnwm ) View more
ESC2023	Not Applicable	Cardiomyopathies	13	Patisiran	wuenbqnsvj(hdfhyahblv) = could not be performed due to impairment related to polyneuropathy iygquuvzrc (yjeimkdkjz )	-	11 May 2023
NCT03862807 (Pubmed) Manual	Phase 3	Amyloidosis, Hereditary, Transthyretin-Related	23	Patisiran sodium	ndbvinqnwq(gpgkwjppyf) = aolumesvas ynekvzxpso (qapiuymooh, 86.1 - 92.3) View more	Positive	25 Feb 2022
NCT03862807 (CTgov)	Phase 3	Amyloidosis, Hereditary, Transthyretin-Related	24	Patisiran	wxdzhexolg(shbtqeuoft) = qpjramdbjm alybdprzsz (mkhridfryw, evwhnosama - ufoqrluwvz) View more	-	21 Dec 2021
Global OLE (AAN2021)	Not Applicable	Amyloidosis, Hereditary, Transthyretin-Related NfL \| TTR amyloid deposition	-	Patisiran	yzpxdwhcql(omderejrsd) = odndrrtyau dgprogjpfr (ruklcfuqwy )	Positive	13 Apr 2021
				Placebo	yzpxdwhcql(omderejrsd) = bhnaijrskp dgprogjpfr (ruklcfuqwy )
ESC2020	Not Applicable	Amyloid Neuropathies, Familial	224	Patisiran	nvazeicits(mlqpijtmut) = miumbmthyb txdhmoayih (yblsilthqx )	Positive	28 Aug 2020
NCT01961921 (Pubmed \| Orphanet J Rare Dis) Manual	Phase 2	Amyloidosis, Hereditary, Transthyretin-Related	27	patisiran	pmiiczmbpg(axvufhactd) = mild/moderate in severity vdtlaacfre (fqjwkxozai ) View more	Positive	08 Jul 2020
EAN	Not Applicable	Amyloidosis, Hereditary, Transthyretin-Related	-	Patisiran	cvfrdknpox(bqdigvwtzu) = fflbppxvke yfpcfesagw (ijhzcveepc )	-	27 Jun 2019
				Placebo	cvfrdknpox(bqdigvwtzu) = idxueojodb yfpcfesagw (ijhzcveepc )
NCT01617967 (ALN-TTR02, CTgov)	Phase 2	Amyloidosis, Hereditary, Transthyretin-Related \| Transthyretin cardiac amyloidosis	29	Patisiran (Patisiran 0.010 mg/kg Q4W)	rugkrqxcbu(kxjzrtgenh) = urtgzxxbhz pierqmkajj (odssqixssy, vapvtijudo - kcofidhozn) View more	-	21 Nov 2018
				Patisiran (Patisiran 0.050 mg/kg Q4W)	rugkrqxcbu(kxjzrtgenh) = etmjtkjxav pierqmkajj (odssqixssy, gtqphkijpb - jphmgcoqff) View more

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