CRISPR therapy tested on more patients with genetic inflammatory disorder

Positive Phase 2 results for an investigational CRISPR genome editing treatment for hereditary angioedema have been announced.

Intellia Therapeutics reported positive outcomes for NTLA-2002, an in vivo CRISPR/Cas-9 therapy that targets inflammation and swelling attacks commonly experienced by hereditary angioedema patients. The findings expand on Phase 1 clinical trial results published this June, where ten patients showed a reduction in swelling attacks after a single dose (see BioNews 1225).

'For many decades, patients with hereditary angioedema were faced with a very limited number of treatment options to control angioedema attacks. The prospect of a potential, functional cure following a single-time treatment is overwhelming both for patients and physicians,' commented Dr Danny Cohn, internist at Amsterdam University Medical Centre, the Netherlands, and first author of the study published in the New England Journal of Medicine.

The researchers conducted a larger study to determine the effective dose of NTLA-2002. The randomised trial included three groups: one received a placebo, while the other two received single doses of 25 mg and 50 mg of the genome-editing drug.

Over a 16-week treatment period, both dosages reduced the average monthly number of swelling attacks, with the 50 mg dose showing a greater reduction compared to the 25 mg dose. Additionally, elevated levels of the protein kallikrein, observed in hereditary angioedema patients, were more reduced in the 50 mg than the 20 mg dosage group. The most common side effects were fatigue and headache.

While the results were viewed as promising by the company, its shares fell by more than 20 percent following the announcement. Analysts attributed this decline to concerns regarding the drug delivery method as it is administered via injection directly into the bloodstream.

'We expect investors will view the approximate 75-80 percent reduction in hereditary angioedema attacks as less than impressive in the context of the potential risks of in vivo gene editing and the competitive landscape in this indication,' analysts commented, noting that other safe and effective drugs for hereditary angioedema treatment are already on the market or awaiting FDA approval.

The company has already begun screening patients for its Phase 3 trial, which will evaluate the efficacy of a single 50 mg dose in a cohort of over 60 participants. Results from this study are expected to be published in 2026.