Intellia CRISPR drug succeeds in late-stage study against rare swelling disorder

Dive Brief:

An experimental gene editing medicine from Intellia Therapeutics has succeeded in a Phase 3 trial, positioning the company to seek approval of what would be the first treatment of its kind for a rare disorder known as hereditary angioedema.
When compared to a placebo, the therapy, “lonvo-z,” reduced the rate of the disease’s hallmark swelling attacks by 87% over the course of about six months, meeting the study’s primary objective. Lonvo-z also helped rid 62% of recipients of disease attacks or the need for other therapies during that follow-up period, versus 11% of placebo patients.
Intellia said, without specifics, that lonvo-z had a “favorable” safety and tolerability profile. The most common treatment-emergent side effects were infusion-related reactions, headache and fatigue, and all reported by a Feb. 10 data cutoff were mild to moderate in degree. The company has begun a “rolling” U.S. approval submission and, assuming a clearance, intends to launch lonvo-z in the first half of 2027. Intellia shares climbed about 5% in early trading Monday.

Dive Insight:

Intellia was one of the first biotech companies built around the Nobel prize-winning, gene editing technology known as CRISPR.

Since then, it’s helped prove that CRISPR can be successfully used inside the body to treat disease, a notable scientific achievement. But Intellia has also burned through billions of dollars and shifted research plans multiple times along the way. The company’s top programs have faced persistent questions about their commercial potential and safety, too.

Lonvo-z is a microcosm of that journey. Intellia billed the therapy as a possible “functional cure” for hereditary angioedema, or HAE, a rare condition that causes swelling attacks that can affect multiple organs. As a one-time, long-lasting treatment, lonvo-z might free people from relying on frequent injections or pills to prevent or treat symptoms.

But genetic medicines have struggled to sell in areas where, as with HAE, multiple effective medicines already exist. Therapies like lonvo-z also carry the specter of certain safety problems — like accidental, off-target edits — that more traditional drugmaking technologies don’t. Those factors have led some analysts to suggest Intellia’s therapy may need to prove exceptionally potent, durable and safe to entice patients and physicians to try it.

The data revealed Monday give Intellia the chance to make that case. Study results showed that, during the treatment period, the average monthly attack rate among lonvo-z recipients was 0.26. That equates to roughly three attacks a year, compared to just over 2 a month for those on a placebo.

Moreover, all patients given lonvo-z in the study were still off other preventive therapy as of that mid-February data cutoff.

Importantly, Intellia didn’t observe the kind of liver-related side effects that have slowed another treatment it’s developing for a rare heart condition. This “clean safety” addresses a key concern among investors on the program and company “as a whole,” wrote Leerink Partners analyst Mani Foroohar. The therapy’s efficacy is “competitive” with CSL’s preventive drug Andembry and could “strengthen over time” with longer follow-up, Foroohar added.

Yet the skepticism about lonvo-z’s sales potential persists. The Food and Drug Administration in the last year has approved multiple new therapies for HAE, giving patients several ways to keep their symptoms at bay.

The ongoing “debate” is now shifting from clinical data to lonvo-z’s “place in the treatment paradigm,” Foroohar wrote.

Evercore ISI analyst Jonathan Miller previously projected that peak annual sales will top out at $500 million, given the way gene therapy launches have gone so far.