NTLA-2002 More and More Looks Like a Cure for HAE

When Intellia Therapeutics set out to develop a CRISPR-based prekallikrein knockout for hereditary angioedema (HAE), it was as a compelling alternative to the newer prophylactic treatments. Cas9 nucleause-based NTLA-2002 (aka lonvo-z) was aimed at having similar efficacy and safety/tolerability, but with the added significant benefits of liberating patients from repeated injections, from having to worry about continued drug reimbursement, all while saving the healthcare system money and resources.

All this is changing as the company is presenting longer-term data strongly suggesting that NTLA-2002 could be a life-time functional cure for many, if not most people living with HAE.

Today, at the EAACI Annual Meeting, Intellia showed that there have been no more HAE attacks since the last update a year ago.  All 10 subjects in this now open-label extension trial have now been attack-free for at least 15 months with a median of almost 2 years.  These 10 patients would have conservatively had around 500 attacks based on their disease history.

500 versus zero, nothing short of a revolution in the management of HAE.  Importantly, with 9 of the 10 subjects having reached 20-30 months after dosing, no drug-related adverse event has been documented after day 28 following NTLA-2002 infusion.

As the data gets better over time, it looks like tonic PKK reduction below a certain threshold may normalize the bradykinin system und put a brake on a neurogenic attack feedback loop.  We know that attacks are frequently triggered by mental and hormonal stress.  In turn, attacks can increase anxiety.  It now looks similar to chronic itch that once the feedback loop is interrupted (HAE attack and scratching) there is a real chance of sustained outcomes.  That this is possible is also illustrated by the fact that people with C1 Inhibitor mutations (the causal mutation in HAE) often do not have any attacks before puberty.

Today’s development illustrates that CRISPR genome editing going after the same targets as competitive modalities can lead to superior outcomes and actually free people from disease instead of keeping them dependent on medicines.  Needless to say, patients are queuing up for the treatment and the pivotal phase 3 trial has been fully enrolled- well ahead of schedule.