FDA Lifts Clinical Hold on Intellia's CRISPR Gene Therapy for Rare Nerve Disease
Key Insights
The FDA has lifted a clinical hold on Intellia Therapeutics' late-stage trial testing nexiguran ziclumeran, a CRISPR-based gene therapy for hereditary transthyretin amyloidosis with polyneuropathy (search) (ATTRv-PN (search)).
The clinical hold was imposed in October after a patient developed severe liver-related side effects, but Intellia has since agreed to stronger safety monitoring measures.
A separate trial testing the same therapy for the cardiac form of the disease remains on hold following a patient death in November.
Intellia Therapeutics received clearance from the U.S. Food and Drug Administration to resume its late-stage gene therapy trial for a rare nerve disease, marking a significant milestone for the company's CRISPR-based treatment program. The FDA lifted the clinical hold on the study testing nexiguran ziclumeran in patients with hereditary transthyretin amyloidosis with polyneuropathy (search) (ATTRv-PN (search)), allowing the company to restart patient enrollment.
The regulatory action sent Intellia's shares surging over 20% in premarket trading, reflecting investor confidence in the company's ability to address safety concerns that had halted the program.
Safety Concerns Addressed Through Enhanced Monitoring
The FDA had imposed the clinical hold in October after a patient in an earlier dosing group developed severe liver-related side effects. To secure the hold's removal, Intellia agreed to implement stronger safety monitoring measures that satisfied regulatory requirements.
"The regulator's decision removes one element of uncertainty and indicates that constructive FDA engagement is ongoing," said Jones Trading analyst Debanjana Chatterjee.
The experimental therapy is designed as a one-time infusion for patients with ATTRv-PN (search), a hereditary condition where a misshapen protein builds up in the nerves and causes progressive damage. The CRISPR-based approach aims to address the underlying genetic cause of the disease rather than just managing symptoms.
Cardiac Trial Remains on Hold
While the nerve disease study has been cleared to proceed, a separate trial testing the same therapy in patients with the cardiac form of the disease, known as cardiomyopathy (search) (ATTR-CM (search)), remains on clinical hold. The patient who experienced liver complications was enrolled in the heart disease study and subsequently died in early November.
Intellia stated it continues working with the FDA on the cardiac program and will provide updates once a path forward is agreed upon. Chatterjee noted that clarity on an FDA-acceptable mitigation plan for the heart disease trial "will be central to how the story evolves from here," given the significantly larger commercial opportunity in that patient population.
Expanded Trial Design and Market Context
The company has expanded the nerve disease trial to enroll approximately 60 patients, up from the original target of 50. The study will compare patients receiving the one-time gene therapy infusion against those receiving a placebo.
Current treatments for the heart-related form of the disease include Alnylam Pharmaceuticals (search)' injectable drug Amvuttra, Pfizer's blockbuster Vyndaqel, and BridgeBio Pharma's Attruby. The competitive landscape underscores the significant unmet medical need in this rare disease area and the potential value of Intellia's gene editing approach if successfully developed.