Intellia Therapeutics Announces First Patient Dosed in the MAGNITUDE-2 Phase 3 Study of Nexiguran Ziclumeran (nex-z), a One-Time Gene Editing-Based Treatment for Transthyretin (ATTR) Amyloidosis with Polyneuropathy
Intellia Therapeutics (NASDAQ:NTLA) has announced the dosing of the first patient in MAGNITUDE-2, a global Phase 3 trial of nexiguran ziclumeran (nex-z) for treating hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). This gene editing-based treatment aims to provide a one-time solution for this progressive, debilitating disease.
The trial builds on promising Phase 1 data that demonstrated nex-z's ability to achieve rapid, deep, and durable reduction in serum TTR levels with a single dose. The company plans to present extended Phase 1 data for both polyneuropathy and cardiomyopathy applications later this year, with a target to submit a biologics licensing application (BLA) for ATTRv-PN by 2028.
Intellia Therapeutics (NASDAQ:NTLA) ha annunciato la somministrazione della prima dose al paziente nel trial globale di Fase 3 MAGNITUDE-2, che riguarda nexiguran ziclumeran (nex-z) per il trattamento dell'amyloidosi ATTR ereditaria con polineuropatia (ATTRv-PN). Questo trattamento basato sull'editing genetico mira a fornire una soluzione unica per questa malattia progressiva e debilitante.
Il trial si basa su dati promettenti della Fase 1 che hanno dimostrato la capacità di nex-z di ottenere una rapida, profonda e duratura riduzione dei livelli sierici di TTR con una singola dose. L'azienda prevede di presentare dati estesi della Fase 1 per le applicazioni relative alla polineuropatia e alla cardiomiopatia entro la fine dell'anno, con l'obiettivo di presentare una domanda di licenza biologica (BLA) per ATTRv-PN entro il 2028.
Intellia Therapeutics (NASDAQ:NTLA) ha anunciado la dosificación del primer paciente en MAGNITUDE-2, un ensayo global de Fase 3 de nexiguran ziclumeran (nex-z) para el tratamiento de la amiloidosis hereditaria ATTR con polineuropatía (ATTRv-PN). Este tratamiento basado en la edición genética tiene como objetivo proporcionar una solución única para esta enfermedad progresiva y debilitante.
El ensayo se basa en datos prometedores de la Fase 1 que demostraron la capacidad de nex-z para lograr una reducción rápida, profunda y duradera de los niveles de TTR en suero con una sola dosis. La empresa planea presentar datos ampliados de la Fase 1 para las aplicaciones de polineuropatía y cardiomiopatía más adelante este año, con el objetivo de presentar una solicitud de licencia biológica (BLA) para ATTRv-PN para 2028.
인텔리아 테라퓨틱스 (NASDAQ:NTLA)는 유전성 ATTR 아밀로이드증과 다발신경병증(ATTRv-PN) 치료를 위한 넥시구란 지클루메란 (nex-z)의 글로벌 3상 시험 MAGNITUDE-2에서 첫 환자에게 투여를 시작했다고 발표했습니다. 이 유전자 편집 기반 치료법은 이 진행성이고 쇠약하게 만드는 질병에 대한 일회성 솔루션을 제공하는 것을 목표로 합니다.
이 시험은 단일 용량으로 혈청 TTR 수치를 빠르고 깊으며 지속적으로 감소시킬 수 있는 nex-z의 능력을 입증한 유망한 1상 데이터에 기반하고 있습니다. 회사는 올해 말까지 다발신경병증 및 심근병증에 대한 1상 데이터를 추가로 발표할 계획이며, 2028년까지 ATTRv-PN에 대한 생물학적 제품 허가 신청(BLA)을 제출할 목표를 가지고 있습니다.
Intellia Therapeutics (NASDAQ:NTLA) a annoncé l'administration de la première dose au patient dans l'essai mondial de Phase 3 MAGNITUDE-2, portant sur nexiguran ziclumeran (nex-z) pour le traitement de l'amyloïdose héréditaire ATTR avec polynévropathie (ATTRv-PN). Ce traitement basé sur l'édition génétique vise à fournir une solution unique pour cette maladie progressive et débilitante.
L'essai s'appuie sur des données prometteuses de la Phase 1 qui ont démontré la capacité de nex-z à obtenir une réduction rapide, profonde et durable des niveaux de TTR sérique avec une seule dose. L'entreprise prévoit de présenter des données étendues de la Phase 1 pour les applications de polynévropathie et de cardiomyopathie plus tard cette année, avec pour objectif de soumettre une demande de licence biologique (BLA) pour ATTRv-PN d'ici 2028.
Intellia Therapeutics (NASDAQ:NTLA) hat die Dosisverabreichung an den ersten Patienten in MAGNITUDE-2 bekannt gegeben, einer globalen Phase-3-Studie zu Nexiguran Ziclumeran (nex-z) zur Behandlung der erblichen ATTR-Amyloidose mit Polyneuropathie (ATTRv-PN). Diese auf Gen-Editing basierende Behandlung zielt darauf ab, eine einmalige Lösung für diese fortschreitende, schwächende Erkrankung zu bieten.
Die Studie baut auf vielversprechenden Phase-1-Daten auf, die gezeigt haben, dass nex-z in der Lage ist, mit einer einzigen Dosis eine schnelle, tiefe und nachhaltige Reduktion der Serum-TTR-Spiegel zu erreichen. Das Unternehmen plant, noch in diesem Jahr erweiterte Phase-1-Daten für die Anwendungen bei Polyneuropathie und Kardiomyopathie zu präsentieren, mit dem Ziel, bis 2028 einen Antrag auf biologische Lizenz (BLA) für ATTRv-PN einzureichen.
- Advancement to Phase 3 trial indicates promising treatment potential
- Phase 1 data showed strong efficacy with rapid, deep, and durable TTR reduction
- Single-dose treatment could replace current chronic treatment regimens
- Clear regulatory pathway with BLA submission targeted for 2028
- Long timeline to potential commercialization (BLA submission not until 2028)
- Phase 3 trial outcomes remain uncertain despite promising Phase 1 data
Insights
The initiation of the Phase 3 MAGNITUDE-2 trial for Intellia's nexiguran ziclumeran (nex-z) represents a significant milestone in the development of CRISPR-based therapeutics for ATTR amyloidosis with polyneuropathy. Advancing to pivotal trials indicates strong confidence based on previous clinical data.
What sets this therapy apart is its one-time treatment paradigm, potentially eliminating the burden of chronic medications currently required for ATTR patients. The Phase 1 data showing "consistently rapid, deep and durable reduction in serum TTR" suggests the therapy effectively targets the disease mechanism, as TTR protein reduction correlates with halting or reversing disease progression.
The 2028 BLA submission timeline indicates this remains a long-term catalyst, with several years of clinical development ahead. While Phase 3 trials represent significant derisking in the drug development process, investors should note that approximately 50
For patients with this progressive disease, a one-time gene editing approach could be transformative compared to existing chronic treatment regimens requiring "pills, injections and infusions." This first patient dosing initiates what will likely be a multi-year pivotal trial program that could position Intellia as a pioneer in bringing CRISPR-based treatments to market for genetic diseases.
This Phase 3 initiation marks a crucial inflection point for Intellia's lead program and validates their gene editing platform in a pivotal setting. With a market cap of just
The single-dose treatment approach for ATTR amyloidosis represents a compelling value proposition against current standard-of-care therapies that require ongoing administration. If successful, nex-z could command premium pricing while reducing overall healthcare expenditure by eliminating lifetime treatment costs.
Investors should note the extended timeline to potential approval, with BLA submission targeted for 2028. This places revenue generation several years away, requiring substantial patience. However, positive longer-term Phase 1 data expected later this year could serve as a nearer-term catalyst.
The polyneuropathy indication represents Intellia's initial market entry strategy, with potential expansion to the larger cardiomyopathy population. This stepwise approach is strategically sound, allowing the company to establish safety and efficacy in a more clearly defined patient population before targeting broader markets.
While development and regulatory risks remain, this Phase 3 initiation substantially derisks Intellia's platform and increases confidence in their ability to translate CRISPR technology into approved therapies.
CAMBRIDGE, Mass., April 03, 2025 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today announced the first patient has been dosed in MAGNITUDE-2, a global, pivotal Phase 3 trial of nexiguran ziclumeran (nex-z) for the treatment of hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN).
“We are pleased to have dosed the first patient with a treatment that has such strong potential to redefine the treatment paradigm for those living with ATTR with polyneuropathy. This is a debilitating, progressive disease that leaves people feeling increasingly helpless,” said Dr. Paulo Sgobbi, Medical Director, PSEG Clinical Research Center. “Through nex-z’s potential to favorably impact disease progression, patients living with ATTR polyneuropathy could experience life-changing benefit while being freed from the existing chronic treatment regimen of pills, injections and infusions.”
“This milestone marks important progress toward our goal of completing the MAGNITUDE-2 clinical program and we are optimistic the study will enable us to demonstrate nex-z’s potential to be the first to halt or reverse disease progression with a single dose in hereditary ATTR with polyneuropathy,” said Intellia President and Chief Executive Officer John Leonard, M.D.
The Phase 3 MAGNITUDE-2 study is informed by Intellia’s Phase 1 data, showing that a single dose of nex-z led to consistently rapid, deep and durable reduction in serum TTR. Intellia expects to present longer-term data from the Phase 1 studies of nex-z for both polyneuropathy and cardiomyopathy later this year. The company plans to submit a biologics licensing application (BLA) for ATTRv-PN by 2028.
About the MAGNITUDE-2 Study
The pivotal Phase 3 MAGNITUDE-2 clinical trial is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of nexiguran ziclumeran (nex-z) in approximately 50 patients with transthyretin amyloidosis with polyneuropathy (ATTRv-PN). The primary endpoint of the study includes a modified neuropathy impairment score and change in serum TTR levels. Adult patients with ATTRv-PN will be randomized 1:1 to receive a single 55 mg infusion of nex-z or placebo. For more information on MAGNITUDE-2 (NCT06672237), please visit clinicaltrials.gov.
About nexiguran ziclumeran (nex-z, formerly 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 an investigational in vivo CRISPR-based therapy designed to inactivate the TTR gene that encodes for the mutated transthyretin (TTR) protein causing the polyneuropathy. Interim Phase 1 clinical data showed the administration of nex-z led to consistent, deep and long-lasting TTR reduction. Nex-z has been granted Regenerative Medicine Advanced Therapy designations by the U.S. FDA for both cardiomyopathy and polyneuropathy. Nex-z has also been granted Orphan Drug Designation by the U.S. FDA and European Commission. Intellia leads development and commercialization of nex-z as part of a multi-target discovery, development and commercialization collaboration with Regeneron.
About Transthyretin (ATTR) Amyloidosis
Transthyretin 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 Therapeutics
Intellia Therapeutics, Inc. (NASDAQ:NTLA) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. Since its inception, Intellia has focused on leveraging gene editing technology to develop novel, first-in-class medicines that address important unmet medical needs and advance the treatment paradigm for patients. 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 concerning: its ability to successfully develop and commercialize nexiguran ziclumeran (“nex-z”), formerly known as NTLA-2001, for the treatment of hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN); the planned release of longer-term data from the Phase 1 studies of nex-z for both polyneuropathy and cardiomyopathy in 2025; its planned submission of a biologics license application (“BLA”) for ATTRv-PN by 2028; the potential of nex-z to be a single-dose treatment and the first treatment to halt or reverse disease progression in ATTRv-PN and for patients to experience life-changing benefit while being freed from chronic treatment; its ability to optimize the impact of its collaborations on its development programs, including its collaboration with Regeneron Pharmaceuticals, Inc. and their co-development program for ATTR amyloidosis.
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 contract manufacturers, 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 and conduct of clinical studies and other development requirements for its product candidates, including nex-z, including uncertainties related to regulatory approvals to conduct clinical trials; risks related to the ability to develop and commercialize nex-z successfully; risks related to the results of preclinical studies or clinical studies not being predictive of future results in connection with future studies; the risk that clinical study results will not be positive; risks related to Intellia’s future financial condition and its ability to fund its operations; and risks related to Intellia’s collaboration with Regeneron Pharmaceuticals, Inc. not continuing or not being 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:
Brittany Chaves
Senior Manager, Investor Relations
brittany.chaves@intelliatx.com
Media:
Matt Crenson
Ten Bridge Communications
media@intelliatx.com
mcrenson@tenbridgecommunications.com
FAQ
What are the key findings from NTLA's Phase 1 trial of nexiguran ziclumeran?
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What makes NTLA's nexiguran ziclumeran different from current ATTR treatments?
What is the significance of the MAGNITUDE-2 Phase 3 trial for NTLA?
