On 31st August 2024, the EPA received a notification from Intellia Therapeutics, Inc., 40 Erie Street, Massachusetts, 02139, USA, seeking consent under Article 14 of the GMO (Deliberate Release) Regulations, S.I. No 500 of 2003, to carry out the deliberate release of a Genetically Modified Organism (GMO).

Description of the GMO and purpose of the deliberate release

The GMO is NTLA-3001, a gene therapy product which will be administered to patients suffering from Alpha-1 Antitrypsin Deficiency (AATD)- associated lung disease. 

NTLA-3001 is derived from wild-type adeno-associated viral vector serotype 8 (AAV8). It carries a therapeutic transgene, SERPINA1. CRISPR-Cas9 gene editing technology will be used to deliver the vector to target cells. Expression of the transgene in target cells will result in the synthesis of the human A1AT (hA1AT) protein to remediate AATD-associated lung disease caused by a lack of functional hA1AT in patients.  

The clinical trial will be carried out in two Phases. Phase 1 will be used to identify a safe and potentially efficacious dose of NTLA-3001. Phase 2 will aim to characterise safety, tolerability, pharmacokinetics and pharmacodynamics of the selected dose level of NTLA-3001, and to provide an initial assessment of NTLA-3001 on clinical measures of pulmonary function. 

Location and Duration

The clinical trials will take place at the following location between 2024 and 2030.

Two Irish sites, Beaumont Hospital, Beaumont Rd., Dublin 9 and St. James’ Hospital, James Street, Dublin 8, will participate in the clinical trial. 

Legislation

Any person or organisation proposing to carry out a deliberate release of a GMO for purposes other than placing on the market (for example, the performance of trials) must comply with the legislative requirements set out under Part II of the GMO (Deliberate Release) Regulations S.I. No 500 of 2003.

Role of the EPA

In accordance with the Regulations, it is the role of the Agency to assess the risks posed by the proposed deliberate release to human health or the environment.
The Agency must respond to the applicant in writing within 90 days of receipt of the notification.  This does not include any period during which the Agency is awaiting a response to a request for further information. In its response to the applicant, the Agency may indicate that consent to the proposed deliberate release is:

  • Granted, with or without conditions, or
  • refused, and the reasons for the refusal.

In reaching its decision, the Agency will take into consideration the views expressed by:

  • the GMO Advisory Committee, a statutory body set up to advise the Agency on any aspect of its functions in relation to GMOs; and,
  • common application form for investigational medicinal products for human use that contain or consist of AAV vectors
  • members of the public in representations forwarded to the Agency in accordance with Article 16 of the Regulations (see also “How to make representations to the EPA about a proposed GM release”);
  • competent authorities of other Member State of the European Communities.
Newspaper notice

The applicant published a notice of the proposed deliberate release, in the Irish Independent (12th September 2024) inviting members of the public to make representations to the EPA within 28 days of publication of the notice in a newspaper (i.e. up to 5pm on 10th October 2024). 

GMO Register Entry

The proposed clinical trial has been assigned GMO Register No G0876-01. The Register provides significant details about the trial.  The register entry will be updated as further details become available.

Relevant Documentation

Summary Notification Information Format (SNIF)
B/IE/24/01
Common Application Form
Newspaper Advertisement
How to make representations to the EPA about a proposed release
GMO Register Entry G0876-01