Clinical trial success moves first in-body CRISPR therapy toward FDA approval

A single-dose CRISPR-based genome-editing therapy for hereditary angioedema has shown positive Phase 3 clinical trial results and entered a step-by-step approval process with US regulators.

Intellia Therapeutics in Cambridge, Massachusetts, reported positive Phase 3 trial results for lonvoguran ziclumeran (lonvo-z), formerly known as NTLA-2002, an experimental in vivo CRISPR/Cas9 therapy for hereditary angioedema, a rare genetic condition that causes severe swelling attacks. The results build on earlier clinical trials, including a ten-patient trial showing reduced swelling attacks after a single dose (see BioNews 1225) and a larger follow-up study assessing the treatment's optimal dose (see BioNews 1263).

'... Many patients continue to experience significant burdens related to the disease, including breakthrough attacks and challenges associated with chronic treatment,' said the principal investigator Professor Aleena Banerji, clinical director of the Allergy and Clinical Immunology Unit at Massachusetts General Hospital and a principal investigator on the HAELO clinical trial. 'The results we are seeing from lonvo-z demonstrate its potential to eliminate the need for chronic medication and related challenges. If approved as a one-time treatment, I would expect lonvo-z to be an appealing option for many patients.'

The randomised, double-blind, placebo-controlled Phase 3 HAELO trial enrolled 80 participants with type I or II hereditary angioedema, who each received either a one-time 50 mg infusion of lonvo-z or a placebo. During the six-month efficacy evaluation period, the therapy reduced swelling attacks by 87 percent compared with placebo, and showed favourable safety and tolerability data, with mostly mild or moderate side effects including infusion-related reactions, headache and fatigue.

Unlike the only currently approved CRISPR-based therapy, Casgevy (see BioNews 1319, 1275 and 1251) – which uses an ex vivo approach in which a patient's cells are edited outside the body and then reinfused – lonvo-z is delivered in vivo via a single infusion, enabling genome editing to occur directly within liver cells. If approved, lonvo-z would likely become the first in vivo CRISPR-based therapy and the second approved CRISPR-based genome-editing therapy overall.

Following the positive Phase 3 results, Intellia Therapeutics began a rolling submission of its Biologics License Application to the US Food and Drug Administration (FDA), allowing the company to submit sections of its approval application for review as they are completed rather than waiting for the full application to be submitted. If approved, Intellia Therapeutics said it expects to launch lonvo-z commercially in the first half of 2027.

'Lonvo-z will become the world's first in vivo CRISPR-based gene editing therapy,' said Dr John Leonard, president and chief executive of Intellia. 'We look forward to our continued engagement with the FDA as we seek to ease many of the burdens for people living with hereditary angioedema.'