Intellia Therapeutics Announces FDA Lift of Clinical Hold on MAGNITUDE Phase 3 Clinical Trial in ATTR-CM
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
News Market Reaction – NTLA
On the day this news was published, NTLA gained 12.05%, reflecting a significant positive market reaction. Argus tracked a peak move of +22.3% during that session. Our momentum scanner triggered 50 alerts that day, indicating high trading interest and price volatility. This price movement added approximately $196M to the company's valuation, bringing the market cap to $1.82B at that time. Trading volume was elevated at 2.0x the daily average, suggesting notable buying interest.
Data tracked by StockTitan Argus on the day of publication.
Key Figures
Market Reality Check
Peers on Argus
NTLA was down 3.5% pre-news while momentum scanner showed only one peer (XERS) moving up, and sector peers like DNTH, ELVN and RCUS were modestly positive. This points to stock-specific dynamics rather than a coordinated sector move.
Previous Clinical trial Reports
| Date | Event | Sentiment | Move | Catalyst |
|---|---|---|---|---|
| Jan 27 | Hold lifted MAG-2 | Positive | +6.3% | FDA lifted clinical hold on MAGNITUDE-2 with safety modifications and resumed enrollment. |
| Nov 10 | ATTR-CM Phase 1 data | Positive | +2.2% | Longer-term Phase 1 data showed deep, durable TTR reductions and clinical stability. |
| Nov 08 | HAE pooled data | Positive | +2.2% | Pooled Phase 1/2 HAE data showed high attack-free rates and strong kallikrein reduction. |
| Oct 27 | MAGNITUDE safety pause | Negative | -42.2% | Severe liver event and trial pause in MAGNITUDE programs after Grade 4 liver injury. |
| Sep 25 | ATTRv-PN Phase 1 data | Positive | -6.5% | Positive long-term ATTRv-PN data with deep TTR reductions but shares fell on the day. |
Clinical trial news has often produced strong one-day moves, including a -42.23% selloff on a safety-related pause and several mid-single-digit gains on positive data or regulatory resolutions. Most clinical updates aligned with their apparent sentiment, with one notable divergence where positive long-term data saw a negative reaction.
Over the past year, NTLA’s key milestones have centered on nexiguran ziclumeran (nex-z) and lonvoguran ziclumeran. For nex-z, the company moved from positive Phase 1 data in ATTR-CM and ATTRv-PN to a serious liver safety event that triggered a pause in the MAGNITUDE programs on Oct 27, 2025, causing a -42.23% reaction. Since then, improved safety clarity and the Jan 27, 2026 lift of the MAGNITUDE-2 hold led to a 6.31% gain, setting the stage for today’s broader hold resolution in ATTR-CM.
Historical Comparison
In the past year, NTLA issued 5 clinical trial updates with an average move of -7.6%, including a -42.23% safety-driven selloff. Today’s FDA lift of the MAGNITUDE ATTR-CM hold follows January’s MAGNITUDE-2 resolution, representing a continuation of the safety and regulatory stabilization narrative for nex-z.
Clinical news has progressed from early positive Phase 1 ATTR data through a serious MAGNITUDE safety event and trial pause, to subsequent FDA engagement and stepwise lifting of holds on MAGNITUDE-2 and now the MAGNITUDE ATTR-CM program.
Market Pulse Summary
The stock surged +12.1% in the session following this news. A strong positive reaction aligns with prior instances where resolution of regulatory overhangs or positive data points supported NTLA shares, such as the 6.31% move on the MAGNITUDE-2 hold lift. Investors would still need to weigh the history of safety concerns, including the -42.23% drop on the MAGNITUDE pause, and assess whether improved monitoring and exclusion criteria in MAGNITUDE meaningfully reduce perceived trial and program risk.
Key Terms
investigational new drug regulatory
clinical hold regulatory
transthyretin amyloidosis medical
cardiomyopathy medical
polyneuropathy medical
ejection fraction medical
double-blind technical
placebo-controlled technical
AI-generated analysis. Not financial advice.
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 <
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
What did Intellia (NTLA) announce on March 2, 2026 about MAGNITUDE Phase 3?
How large is the MAGNITUDE Phase 3 trial for NTLA's nex-z and what is the dosing?
Why was the MAGNITUDE IND put on hold in October 2025 for Intellia (NTLA)?
What safety measures did Intellia (NTLA) agree with the FDA for MAGNITUDE and MAGNITUDE-2?
What is MAGNITUDE-2 and how many patients will NTLA enroll in that trial?
