RARE Daily

Intellia Cleared to Dose First Patient with Potentially Curative Gene Editing Therapy for hATTR-PN

October 20, 2020

Rare Daily Staff

Intellia Therapeutics said it has secured authorization from the United Kingdom Medicines and Healthcare products Regulatory Agency to begin a phase 1 study that will evaluate its experimental therapy NTLA-2001 for the treatment of the rare, progressive, and fatal condition hereditary transthyretin amyloidosis with polyneuropathy.

Hereditary ATTR (hATTR) occurs when a person is born with a specific DNA mutation in the TTR gene, which causes the liver to produce a protein called transthyretin (TTR) in a misfolded form that builds up in the body. hATTR can manifest as polyneuropathy (hATTR-PN), which can lead to nerve damage, or cardiomyopathy (hATTR-CM), which involves heart muscle disease that can lead to heart failure. In addition, non-mutated, or wild-type TTR protein, can also accumulate in the body, leading to wild-type ATTR (wtATTR). There are an estimated 50,000 hATTR patients worldwide and between 200,000 and 500,000 people with wtATTR.

Intellia’s NTLA-2001, its lead therapeutic candidate, could be the first curative treatment for ATTR. By applying the company’s in vivo liver knockout technology, Intellia said it has the potential to result in lifelong transthyretin (TTR) protein reduction after a single course of treatment. The therapy is delivered via Intellia’s proprietary non-viral lipid nanoparticle platform, which the company is also using to develop in vivo treatments for other diseases.

“Our trial is the first step toward demonstrating that our therapeutic approach could have a permanent effect, potentially halting and reversing all forms of ATTR,” said Intellia’s President and CEO John Leonard. “Once we have established safety and the optimal dose, our goal is to expand this study and rapidly move to pivotal studies, in which we aim to enroll both polyneuropathy and cardiomyopathy patients.”

The company expects to dose the first patient in the phase 1 trial by the end of 2020, subject to the impact of the COVID-19 pandemic. Intellia’s global first-in-human trial will be an open-label, multi-center, two-part study of NTLA-2001 in adults with hATTR-PN, the hereditary form of amyloidosis with peripheral nerve damage. The study will enroll up to 38 patients and consist of a single-ascending dose phase in part 1 and, following the identification of an optimal dose, a single-cohort expansion in part 2.

The trial will assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of NTLA-2001, which will include the measurement of serum TTR levels following a single intravenous infusion. The secondary objectives are to evaluate the efficacy of NTLA-2001 on clinical measures of neurologic function in hATTR-PN patients.

Beyond its first application in the United Kingdom, Intellia is submitting additional regulatory applications in other countries as part of its ongoing, global development strategy. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia and Regeneron Pharmaceuticals.

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