Intellia's CRISPR candidate continues to cut HAE attacks at year follow-up

2023-06-12

临床结果临床1期临床2期

Intellia Therapeutics said new data show that across all 10 hereditary angioedema (HAE) patients who received a single dose of its in vivo CRISPR genome editing therapy in a Phase I/II study, the average reduction in monthly HAE attack rate was 95% through the latest follow-up. New findings for the NTLA-2002 treatment were reported over the weekend at the European Academy of Allergy and Clinical Immunology (EAACI) congress.

"The earliest-dosed patients are attack free for approximately a year or longer, with NTLA-2002 demonstrating a very favourable safety profile," commented CEO John Leonard, adding that the benefit has been "consistent, even in patients with the most severe symptoms."

NTLA-2002 works by knocking out KLKB1 gene expression in order to block production of kallikrein and ultimately prevent HAE attacks. In the Phase I portion of the study, single doses of 25mg, 50mg and 75mg of NTLA-2002 were administered via intravenous infusion, and HAE attacks and plasma kallikrein protein levels were measured for each patient.

Last November, the company said patients had achieved mean reductions of 89% in HAE attack rate from weeks 5 to 16, with Leonard suggesting at the time that NTLA-2002 offered the possibility of a "functional cure." According to the latest results, which had a February 17 cut-off, NTLA-2002 reduced average monthly HAE attack rates by 92% across all three groups from weeks 5 to 16. The 50mg cohort had the best showing, with all four patients being free of HAE attacks over that period.

Attack-free interval of 13 months

In addition, over the on-study period – the time from NTLA-2002 dosing through to the last assessment – the monthly HAE reduction was at least 93%, with the 50mg again performing best, achieving a reduction of 98%. The duration of follow-up ranged from close to 6 months to just over 14 months. Intellia noted that the longest attack-free interval is "13 months and ongoing."

Further, all nine patients who achieved >60% plasma kallikrein reduction remain attack-free following the 16-week primary observation period through the latest follow-up. Six subjects had also stopped long-term prophylaxis treatment after they got NTLA-2002, and Intellia said they have so far not experienced any more HAE attacks. Meanwhile, NTLA-2002 led to dose-dependent reductions in plasma kallikrein, ranging from 67% to 95%.

The majority of adverse events were mild, with no dose-limiting toxicities, no serious adverse events or any abnormal laboratory findings in any of the patients. Side effects were typically related to infusion-related reactions and fatigue, and resolved within two days, according to the company. The Phase II portion of the trial began dosing patients earlier this year, and Intellia expects to complete enrollment in the second half.

Ionis drug one to beat

Analysts at BMO Capital markets said data from the 50mg cohort "suggest durability of effect," although they noted that these patients had low disease severity, compared with the other two cohorts. "Overall, we believe that the 75mg dose data are reflective of the 50mg cohort and point to a durable/safe NTLA-2002 profile," the analysts said.

Still, they anticipate Ionis Pharmaceuticals' donidalorsen will be the leading therapy in HAE prophylaxis. The investigational ligand-conjugated antisense therapy, which is designed to target the prekallikrein pathway, recently showed a 97% attack reduction rate starting with the second dose. However, BMO analysts said the new data on NTLA-2002 suggest it is likely to capture "a meaningful market share."

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