Intellia’s CRISPR Drug Claims FDA Orphan Drug Designation to Treat ATTR Amyloidosis

Intellia Therapeutics is pushing CRISPR gene editing deeper into the human body. The US-based company, co-founded by Nobel laureate Jennifer Doudna, announced that the FDA has granted Orphan Drug Designation to NTLA-2001, its treatment for transthyretin (ATTR) amyloidosis.

ATTR amyloidosis is a rare protein misfolding disorder originating in the liver. Normally, the liver makes a protein called transthyretin to carry thyroid hormone and Vitamin A in the blood. However, a mutation in the TTR gene (which encodes transthyretin) causes the protein to break down.

The unstable proteins “misfold,” binding to each other and forming amyloid fibrils, which are deposited in blood vessels, nerves, and organs. The buildup of fibrils disrupts organ function, possibly leading to life-threatening situations.

NTLA-2001 is jointly developed by Intellia and Regeneron Pharmaceuticals as a one-time treatment that could halt and reverse the progression of the disease. Designed to knock out the TTR gene to bring concentrations of mutated transthyretin down, the drug has shown promise in a Phase 1 trial.

How Intellia’s Drug Compares to Other Treatments for ATTR Amyloidosis

There are already a number of approved treatments that silence the TTR gene to treat ATTR amyloidosis. 

Onpattro (patisiran), developed by Alnylam, inactivates TTR by binding to its mRNA through the RNA interference (RNAi) pathway. It was also the first FDA-approved drug to use RNAi technology. Another drug, Tegsedi (inotersen), operates in a similar vein.

However, these are multi-dose treatments. Onpattro has to be given once every three weeks, while Tegsedi is a weekly injection.

Intellia is hoping that the single-dose treatment NTLA-2001 would be its main selling point.

On the efficacy front, an interim readout in the Phase 1 trial of NTLA-2001 found that a single 0.3 mg/kg dose of the drug on average reduced transthyretin in the blood serum by 87%. In comparison, the standard of care treatments such as Onpattro reduced levels of the mutated protein by around 80%.

NTLA-2001 was generally well-tolerated, with no serious adverse events or liver abnormalities recorded by Day 28. The results were published in the New England Journal of Medicine.

Julian Gillmore, the national coordinating investigator for the Phase 1 trial, had called the results “highly encouraging.”

“These interim Phase 1 data support NTLA-2001 as the only one-time treatment either on the market or in development,” he said.

How Orphan Drugs Benefit Their Developers 

Developers of orphan drugs are given development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions, and seven-year marketing exclusivity upon FDA approval.

The decision by the FDA follows a similar one given earlier by the European Commission. In March, the EC granted NTLA-2001 orphan drug designation for the same disease setting.

“Orphan drug designation underscores the FDA’s recognition of NTLA-2001’s potential promise as a single-dose, novel therapy for the treatment of ATTR amyloidosis,” said Intellia President and CEO, John Leonard, M.D.

Author

Joy Lin

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