One-shot CRISPR treatment for inherited disease aces first human trial

A CRISPR treatment for hereditary angioedema has just performed incredibly well in its first human trial. If the results are confirmed in larger studies, it could be the first one-and-done therapy for the painful swelling disorder. 

The disease: Hereditary angioedema is a rare but serious disorder that causes severe swelling in the hands, feet, face, and other parts of the body. Sometimes, these attacks can be caused by stress or physical trauma, but they often happen for no apparent reason.

“It’s transforming patients’ lives.”

Padmalal Gurugama

If untreated, it’s common for someone with hereditary angioedema to have three or more attacks every month. The attacks can last for several days, making it hard to live a “normal” life, and if the swelling hits their airway, it can even be fatal.

While there are drugs designed to prevent attacks, they have to be taken daily (if in pill form) or every few days (if administered via IV). They aren’t 100% effective, either, meaning people on them may still have to  worry that an attack is coming — and that stress can lead to more attacks. 

“Amazing”: Intellia Therapeutics, an early pioneer in gene editing, is developing a CRISPR treatment for hereditary angioedema — and the results of their phase 1 trial suggests it could be the first one-and-done therapy for the devastating condition.

“It’s transforming patients’ lives,” study co-author Padmalal Gurugama told the Guardian. “My patient was having attacks every three weeks and that gentleman has not had any attacks in the past 18 months. He is not taking any medications. That is amazing.”

How it works: People with hereditary angioedema have a genetic mutation that prevents their body from making a blood protein called “C1-Inhibitor.” This leads to the buildup of another protein, called “kallikrein,” which is what triggers their swelling attacks.

Intellia’s CRISPR treatment, called “NTLA-2002,” works by inactivating a gene in the liver that’s necessary for the production of kallikrein.

In the phase 1 trial, 10 people with hereditary angioedema received a single IV infusion of the therapy in one of three doses: 25 mg, 50 mg, and 75 mg. In the 16-week observation period that followed, their rate of attacks fell by an average of 95%.

The six participants who were taking preventative meds prior to enrolling in the study have stopped, and nine participants had no attacks between the end of the observation period and the last check-in (the follow-up ranged from 5.7 months to 13.1 months after treatment).

The therapy was well tolerated, with no serious adverse events reported.

Looking ahead: Intellia is wasting no time in trialing its CRISPR treatment in larger populations — a placebo-controlled phase 2 trial is ongoing, with results expected later in 2024, and the company is working with regulators to kick off a phase 3 trial before the end of the year.

If the drug is eventually approved, gene therapies are usually incredibly expensive — Casgevy, the only FDA-approved CRISPR therapy to date, comes with a $2.2 million price tag — so access will likely be extremely limited, at least at first.

But for those lucky enough to receive the treatment, the results could be life-changing.

“I’ve had a radical improvement in my physical and mental wellbeing,” Cleveland, a 54-year-old trial participant who has been attack-free for 18 months, told the Guardian, adding, “I spent my life constantly wondering if my next attack would be severe.”

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