FDA Grants RMAT Designation to Intellia's Nex-Z for Hereditary ATTR Amyloidosis Treatment

Intellia Therapeutics, Inc. (NASDAQ: NTLA), a prominent clinical-stage gene editing company, has announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to nexiguran ziclumeran (nex-z, also known as NTLA-2001). This investigational CRISPR-based therapy aims to treat hereditary transthyretin (ATTR) amyloidosis with polyneuropathy (ATTRv-PN). Nex-z is designed as a one-time treatment to deactivate the TTR gene, thereby preventing the production of the TTR protein, which is responsible for ATTR amyloidosis. Intellia is leading the development and commercialization of nex-z through a partnership with Regeneron.

John Leonard, M.D., President and CEO of Intellia, emphasized the significance of the RMAT designation, stating that it highlights the transformative potential of nex-z. The FDA granted this designation following a review of interim Phase 1 data, which demonstrated that the one-time treatment resulted in rapid, substantial, and long-lasting TTR reduction. This reduction is expected to halt and possibly reverse the progression of the disease. Intellia plans to work closely with the FDA to expedite the availability of this therapy for patients.

The RMAT designation, created under the 21st Century Cures Act, is intended to speed up the development and review of promising therapeutic candidates, including genetic therapies, aimed at treating or curing serious or life-threatening diseases. Benefits of RMAT designation include early interactions with the FDA, discussions on surrogate or intermediate endpoints that could support accelerated approval, and potential priority review of a product’s biologics license application (BLA).

This recent RMAT designation is the third special regulatory recognition for nex-z. Previously, the therapy received Orphan Drug Designation from both the U.S. FDA and the European Commission. Nex-z is based on the Nobel Prize-winning CRISPR/Cas9 technology and has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis. Data from interim Phase 1 clinical trials indicated that administering nex-z consistently leads to significant and durable reductions in TTR levels. Intellia is leading the development and commercialization of nex-z through its collaboration with Regeneron.

Transthyretin amyloidosis (ATTR amyloidosis) is a rare, progressive, and fatal disease. Hereditary ATTR (ATTRv) amyloidosis arises from mutations in the TTR gene, leading the liver to produce structurally abnormal TTR proteins that tend to misfold. These misfolded proteins accumulate as amyloid deposits in various tissues, causing severe complications in the heart, nerves, and digestive system. ATTRv amyloidosis primarily presents as polyneuropathy (ATTRv-PN), causing nerve damage, or cardiomyopathy (ATTRv-CM), leading to heart failure. Some individuals produce non-mutated, or wild-type TTR proteins that become unstable over time, leading to wild-type ATTR (ATTRwt) amyloidosis, which mainly affects the heart. Approximately 50,000 people globally are affected by ATTRv amyloidosis, while an estimated 200,000 to 500,000 people are affected by ATTRwt amyloidosis. There is currently no cure for ATTR amyloidosis, and existing medications only slow the accumulation of misfolded TTR proteins.

Intellia Therapeutics, Inc. is at the forefront of clinical-stage gene editing, focusing on developing CRISPR-based therapies to revolutionize medicine. The company's in vivo programs facilitate precise editing of disease-causing genes directly within the human body, while its ex vivo programs engineer human cells outside the body for treating cancer and autoimmune diseases. Intellia's extensive scientific, technical, and clinical expertise is setting a new standard in medicine. The company continues to enhance its CRISPR-based platform with innovative editing and delivery technologies.