Intellia Obtains UK Clearance to Begin Gene Insertion Trial in Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) is a rare, incurable genetic condition that increases the risk of developing severe lung and liver disease, including emphysema, cancer, and organ failure. The disease arises through mutations in the SERPINA1 gene that either reduce the quantity or impact the functionality of the alpha-1 antitrypsin (AAT) protein, which is produced by the liver and protects the lungs. Accumulation of abnormal AAT in the liver causes hepatic damage over time. The disease is estimated to affect approximately 250,000 individuals worldwide.

Current treatment approaches predominantly aim to control symptoms and reduce risk factors. Augmentation therapy, a lifelong treatment involving the administration of AAT protein derived from donor blood, can increase AAT levels in the lungs and slow lung damage, though it does not prevent liver damage. Lung and liver transplants may be an option for patients with severe disease, although donor organs are not easy to obtain and the surgeries carry a high risk of complications.

NTLA-3001 is a potential one-shot curative treatment for AATD

Intellia Therapeutics is developing NTLA-3001 as a potential single-dose treatment to normalise AAT protein levels and halt the progression of lung disease associated with AATD. Yesterday, the company announced in a press release that the UK's Medicines and Healthcare products Regulatory Agency has cleared its clinical trial application for NTLA-3001, which means that Intellia can now initate a clinical trial of NTLA-3001 in the UK.

NTLA-3001 is an in vivo CRISPR-Cas9-based targeted gene insertion candidate designed to precisely insert a healthy copy of the SERPINA1 gene. The approach has the potential to restore permanent expression of functional AAT protein to therapeutic levels after a single dose, and if successful, will transform the lives of AATD patients by eliminating the need for weekly AAT augmentation therapy or lung transplantation in severe cases.

According to the same press release, NTLA-3001 is Intellia’s first wholly owned CRISPR-based in vivo targeted gene insertion candidate to advance into the clinic, and the company is on track to dose the first patient in the second half of 2024.

The NTLA-3001 trial - what we know so far

The Phase 1/2 study will be an international, multicenter, single-arm, open-label study in adults with AATD-associated lung disease. The study will enrol up to 30 patients and include a dose-escalation phase and a dose-expansion phase to confirm the recommended dose. The study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of NTLA-3001. Intellia also announced in its press release that it is submitting additional regulatory applications in other countries as part of its ongoing, multi-national development strategy for NTLA-3001.

NTLA-3001 is the second gene-editing candidate to enter clinical development for AATD. Earlier this month, Beam Therapeutics announced that it has dosed the first AATD patient with its base-editing candidate BEAM-302. This is an in vivo liver-targeting base-editing therapy designed to precisely correct the PiZ mutation, a single point mutation found in the majority of severe homozygous patients living with AATD. You can read more about that programme here.

Stay tuned for more updates

We will continue to update you on the gene-editing clinical trials as new details emerge. In the meantime, can find all of our coverage on clinical-stage gene editing programmes here.

For a complete overview of current gene editing clinical trials, check out CRISPR Medicine News' Clinical Trials Database.