Intellia Therapeutics Announces FDA Lift of Clinical Hold on MAGNITUDE Phase 3 Clinical Trial in ATTR-CM

Intellia Therapeutics (Nasdaq: NTLA) announced the FDA has lifted the clinical hold on the IND for the MAGNITUDE Phase 3 trial of nexiguran ziclumeran (nex-z) in ATTR-CM, allowing enrollment to resume with enhanced safety measures.

Rhea-AI Summary

Intellia Therapeutics (Nasdaq: NTLA) announced the FDA has lifted the clinical hold on the IND for the MAGNITUDE Phase 3 trial of nexiguran ziclumeran (nex-z) in ATTR-CM, allowing enrollment to resume with enhanced safety measures.

Holds were originally placed on October 29, 2025 after a patient experienced Grade 4 liver transaminase elevations and increased bilirubin. Mitigations include intensified liver monitoring, short-term steroid guidance, new exclusion criteria (including ejection fraction <25% and recent cardiovascular instability), and exclusion for certain liver abnormalities. MAGNITUDE plans ~1,200 patients (2:1 randomization, single 55 mg infusion); MAGNITUDE-2 enrolls ~60 ATTRv-PN patients (1:1).

Positive

• FDA lifted clinical hold on MAGNITUDE IND
• MAGNITUDE plans approximately 1,200 patients
• MAGNITUDE-2 plans approximately 60 patients
• Enrollment resumption expected after safety mitigations

Negative

• Observed Grade 4 liver transaminases and increased bilirubin
• New exclusion criteria may reduce eligible patient pool
• Enhanced monitoring implies prior safety signal for nex-z

Argus Mar 2 session

+12.05% close to close Open Argus

Details

News Market Reaction – NTLA

On Mar 2, the day this news came out, NTLA closed 12.05% above the previous close.

Data tracked by StockTitan Argus for the Mar 2 session.

Key Figures

MAGNITUDE enrollment: approximately 1,200 patients MAGNITUDE-2 enrollment: approximately 60 patients Dose per patient: 55 mg +4 more

MAGNITUDE enrollment

approximately 1,200 patients

Phase 3 ATTR-CM trial target population

MAGNITUDE-2 enrollment

approximately 60 patients

Phase 3 ATTRv-PN trial target population

Dose per patient

55 mg

Single IV infusion of nex-z in both Phase 3 trials

MAGNITUDE randomization

2:1 nex-z vs placebo

Phase 3 ATTR-CM trial design

MAGNITUDE-2 randomization

1:1 nex-z vs placebo

Phase 3 ATTRv-PN trial design

Ejection fraction cutoff

<25%

Exclusion criterion at screening for MAGNITUDE

Clinical hold date

October 29, 2025

Date FDA imposed holds on MAGNITUDE and MAGNITUDE-2 INDs

Previous Clinical trial Reports

5 past events · Latest: Jan 27

Same Type 5 events

1. Jan 27

   Hold lifted MAG-2

   24h Move

   +6.3%

   FDA lifted clinical hold on MAGNITUDE-2 with safety modifications and resumed enrollment.

2. Nov 10

   ATTR-CM Phase 1 data

   24h Move

   +2.2%

   Longer-term Phase 1 data showed deep, durable TTR reductions and clinical stability.

3. Nov 08

   HAE pooled data

   24h Move

   +2.2%

   Pooled Phase 1/2 HAE data showed high attack-free rates and strong kallikrein reduction.

4. Oct 27

   MAGNITUDE safety pause

   24h Move

   -42.2%

   Severe liver event and trial pause in MAGNITUDE programs after Grade 4 liver injury.

5. Sep 25

   ATTRv-PN Phase 1 data

   24h Move

   -6.5%

   Positive long-term ATTRv-PN data with deep TTR reductions but shares fell on the day.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Key Terms

investigational new drug, clinical hold, transthyretin amyloidosis, cardiomyopathy, +4 more

8 terms

investigational new drug regulatory

"FDA has removed the clinical hold on the Investigational New Drug application (IND)"

An investigational new drug is a medication that is still being tested in clinical trials to determine if it is safe and effective for treating a specific condition. For investors, it represents a potential breakthrough that could lead to a new treatment and significant financial gains if successful, but also carries risks since it has not yet been approved for widespread use.

clinical hold regulatory

"FDA has removed the clinical hold on the Investigational New Drug application (IND)"

A clinical hold is an order from a drug or medical-device regulator to stop or suspend a clinical trial or development activity because of safety concerns, inadequate study plans, or incomplete data. Think of it like a referee pausing a game until rules or safety issues are resolved; investors care because a hold can delay approval, increase costs, create uncertainty about a product’s future, and often affects a company’s valuation until the issues are addressed.

transthyretin amyloidosis medical

"for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM)"

A progressive disease caused when a normal blood protein called transthyretin misfolds and forms sticky clumps that build up in organs such as the heart and nerves, impairing their function. It matters to investors because diagnosing and treating it often requires specialized drugs, tests and long-term care, so clinical trial results, regulatory approvals, or new diagnostic tools can materially affect healthcare companies’ revenues and the potential market size for therapies.

cardiomyopathy medical

"transthyretin amyloidosis with cardiomyopathy (ATTR-CM)"

A condition that weakens or stiffens the heart muscle, reducing its ability to pump blood effectively; think of the heart as an engine that becomes less powerful or less flexible. For investors, cardiomyopathy matters because it can drive demand for medical treatments, affect healthcare costs, influence the value of companies developing drugs or devices, and trigger regulatory or insurance impacts that change revenues and risks across the healthcare sector.

polyneuropathy medical

"hereditary ATTR with polyneuropathy, our attention now turns"

Polyneuropathy is a condition in which many nerves outside the brain and spinal cord stop working properly, causing numbness, tingling, weakness or pain in the hands, feet or limbs. Think of it like the electrical wiring in a house developing multiple shorts — it impairs communication and function. For investors, its presence, prevalence or treatment advances can affect demand, regulatory outcomes and the commercial value of drugs, devices or diagnostic tests targeting nerve damage.

ejection fraction medical

"those with ejection fraction <25% at the time of screening"

Ejection fraction is the percentage of blood the heart’s main pumping chamber pushes out with each beat, measured by imaging tests; think of it as the share of liquid emptied from a glass when you pour. Investors monitor it because changes signal shifting demand for treatments, devices, insurance and workforce health, and because clinical results or regulatory decisions tied to ejection fraction often influence healthcare and related stocks.

double-blind technical

"MAGNITUDE is a randomized, double-blind, placebo-controlled trial"

A double-blind process means that neither the people conducting an activity nor the people involved know certain key details, such as who is receiving a treatment or a placebo. This approach helps prevent bias from influencing the results, making the outcome more trustworthy. For investors, it ensures that decisions or judgments are based on unbiased information rather than preconceived opinions or expectations.

placebo-controlled technical

"randomized, double-blind, placebo-controlled trial evaluating the efficacy"

"Placebo-controlled" describes a testing method where one group receives the actual treatment or intervention, while another group receives a harmless, inactive version called a placebo. This approach helps determine whether the real treatment has genuine effects beyond psychological expectations. For investors, understanding this ensures confidence that reported benefits are real and not influenced by bias or false perceptions.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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CAMBRIDGE, Mass., March 02, 2026 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (Nasdaq: NTLA), a leading biopharmaceutical company focused on revolutionizing medicine leveraging CRISPR gene editing and other core technologies, today announced that the U.S. Food and Drug Administration (FDA) has removed the clinical hold on the Investigational New Drug application (IND) for the MAGNITUDE Phase 3 clinical trial of nexiguran ziclumeran (nex-z) for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM).

“We are very pleased to have aligned with the FDA on the path forward for our MAGNITUDE clinical trial, with measures designed to further enhance patient safety and allow us to continue to investigate nex-z in a broad ATTR-CM population,” said Intellia President and Chief Executive Officer John Leonard, M.D. “With the resolution in January of the clinical hold on our MAGNITUDE-2 Phase 3 trial for patients with hereditary ATTR with polyneuropathy, our attention now turns to completing enrollment in both ongoing trials. We appreciate the FDA’s responsiveness throughout this process and thank the many investigators and patients who are participating in these trials.”

The clinical holds on the INDs for MAGNITUDE and MAGNITUDE-2 were imposed by the FDA on October 29, 2025, following the observation of Grade 4 liver transaminases and increased total bilirubin in a patient who was dosed with nex-z in MAGNITUDE that met the trial’s protocol-defined pausing criteria. The company has aligned with the FDA on mitigation measures for MAGNITUDE and MAGNITUDE-2 that include enhanced monitoring of liver laboratory tests, guidance for short-term steroid treatment if elevated liver transaminases are observed in the initial period following dosing and the exclusion of patients with certain liver abnormalities. For MAGNITUDE, additional exclusion criteria are being incorporated for patients with a recent history of cardiovascular instability and those with ejection fraction <25% at the time of screening. Intellia is engaged with clinical trial investigators, ethics committees, international regulatory authorities and other stakeholders to resume enrollment activities in MAGNITUDE and MAGNITUDE-2.

MAGNITUDE is a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of nex-z in approximately 1,200 patients with ATTR-CM. The primary endpoint of the trial is based on a composite measure of cardiovascular-related events, including mortality. Adult patients with ATTR-CM are randomized 2:1 to receive a single 55 mg infusion of nex-z or placebo. For more information on MAGNITUDE (NCT06128629), please visit clinicaltrials.gov.

MAGNITUDE-2 is a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of nex-z in approximately 60 patients with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). The primary endpoints of the study are a change in modified neuropathy impairment score and a change in serum TTR levels. Adult patients with ATTRv-PN are 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 Nex-z
Based on Nobel Prize-winning CRISPR/Cas9 gene editing technology, nex-z has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis with cardiomyopathy (ATTR-CM) and/or hereditary ATTR with polyneuropathy (ATTRv-PN). Nex-z is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein and is being investigated in MAGNITUDE and MAGNITUDE-2, Phase 3 clinical trials in ATTR-CM and ATTRv-PN, respectively. Interim Phase 1 clinical data showed the administration of nex-z led to consistent, deep and long-lasting TTR reduction. Nex-z has received an Orphan Drug and RMAT Designation from the U.S. Food and Drug Administration (FDA) and an Orphan Drug Designation (ODD) from the European Commission. Intellia leads development and commercialization of nex-z as part of a multi-target discovery, development and commercialization collaboration with Regeneron Pharmaceuticals, Inc. 

About Intellia Therapeutics
Intellia Therapeutics, Inc. (Nasdaq: NTLA) is a leading clinical-stage biopharmaceutical company focused on revolutionizing medicine leveraging CRISPR gene editing and other core technologies. The company’s mission is to transform the lives of people with severe diseases by developing and commercializing potentially curative treatments. With deep scientific, technical and clinical development experience, Intellia aims to reset the standard for medicine by durably treating the root causes of disease. Learn more at intelliatx.com and follow us @intelliatx.

Forward-Looking Statements
This press release contains “forward-looking statements” of Intellia Therapeutics, Inc. (“Intellia” or the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellia’s beliefs and expectations regarding: the safety, tolerability, efficacy, success and advancement of its clinical programs for nexiguran ziclumeran or “nex-z” (also known as NTLA-2001), including the ability to engage with clinical trial investigators, ethics committees, international regulatory authorities and other stakeholders to resume enrollment activities in its MAGNITUDE and MAGNITUDE-2 trials for nex-z in ATTR-CM and ATTRv-PN, the ability to successfully complete the MAGNITUDE and MAGNITUDE-2 trials, and the potential of nex-z to become the first one-time treatment for ATTR-CM and/or ATTRv-PN.

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: regulatory agencies’ evaluation of regulatory filings and other information related to our product candidates, including nex-z; uncertainties related to the authorization, initiation and conduct of studies and other development requirements for our product candidates, including uncertainties related to regulatory approvals to conduct clinical trials; the risk that any one or more of Intellia’s product candidates, including nex-z, will not be successfully developed and commercialized; risks related to Intellia’s ability to protect and maintain its intellectual property position; risks related to valid third party intellectual property; risks related to Intellia’s relationship with third parties, including its licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies for the same product candidate or Intellia’s other product candidates; and risks related to Intellia’s reliance on collaborations, including that its collaboration with Regeneron Pharmaceuticals, Inc. will not continue or will not be successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellia’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Intellia’s most recent annual report on Form 10-K and quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in Intellia’s other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law.

Contact:
Jason Fredette
Vice President, Investor Relations and Corporate Communications
Intellia Therapeutics, Inc.
jason.fredette@intelliatx.com

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Intellia (NTLA) announce on March 2, 2026 about MAGNITUDE Phase 3?

The FDA removed the IND clinical hold for MAGNITUDE, allowing enrollment to resume. According to the company, this follows agreement on enhanced liver monitoring, steroid guidance and added exclusion criteria to address a prior liver safety event.

How large is the MAGNITUDE Phase 3 trial for NTLA's nex-z and what is the dosing?

MAGNITUDE will enroll about 1,200 patients randomized 2:1 to nex-z or placebo. According to the company, adults receive a single 55 mg infusion and the primary endpoint is a composite of cardiovascular events including mortality.

Why was the MAGNITUDE IND put on hold in October 2025 for Intellia (NTLA)?

The hold followed a patient with Grade 4 liver transaminase elevations and increased total bilirubin meeting protocol pausing criteria. According to the company, the events prompted FDA-imposed holds while safety mitigations were developed and agreed.

What safety measures did Intellia (NTLA) agree with the FDA for MAGNITUDE and MAGNITUDE-2?

Measures include enhanced liver lab monitoring, short-term steroid guidance for early transaminase rises, and exclusion of patients with certain liver abnormalities. According to the company, MAGNITUDE also adds exclusions for recent cardiovascular instability and EF <25%.

What is MAGNITUDE-2 and how many patients will NTLA enroll in that trial?

MAGNITUDE-2 is a randomized trial in hereditary ATTR with polyneuropathy planning about 60 patients randomized 1:1. According to the company, endpoints include modified neuropathy impairment score changes and serum TTR level changes.