Intellia tacks on lower dose to polyneuropathy trial arm after elevated liver level in one patient

With over $900 million in the bank and much of its pipeline progressing as planned, Intellia looked to be sailing smoothly amid the tumultuousness of clinical development. But they've still had to make a couple of pipeline amendments to remain on course.

Of the two switch-ups revealed by the gene-editing company in its second-quarter earnings report Thursday, the most notable change is that Intellia is looking to add a lower fixed dose level to the polyneuropathy arm of the trial testing a therapy called NTLA-2001 in patients with transthyretin (ATTR) amyloidosis. The company made the call after one patient reported elevated liver enzyme levels 28 days after treatment.

The elevated levels were “possibly related” to the drug, the company said, but on its earnings call executives tamped that down further, saying they “have no idea” whether it was linked to treatment. NTLA-2001 is part of a collaboration with Regeneron

The patient was asymptomatic, and the side effect was deemed “nonserious” by the trial investigator, Intellia said in its earnings announcement. Nonetheless, the company plans to add a fixed dose arm corresponding to 0.7 mg/kg to counteract any potential impact the 1.0 mg/kg fixed-dose may have had on adverse events. The company expects that it will still be able to meet its previously announced timeline of wrapping up enrollment before the end of the year. 

Intellia executives said they are confident that a lower dose can pack an equal punch, citing interim data from the cardiomyopathy arm showing similar serum transthyretin (TTR) level reduction at both the 0.7 and 1.0 dose levels. 

“Because we believe we have so much room on the efficacy side … backing off the dose is a reasonable thing to do, particularly since our database has grown,” said CEO John Leonard, M.D., on the call.

In addition to amending the ATTR trial, Intellia has decided to push all of its oncology chips toward “off-the-shelf” work, electing to end the development of NTLA-5001, an autologous T-cell receptor therapy. Dosing for that trial began in March.

Instead, the company says it’s going to focus all of its ex vivo work on allogeneic treatments—where the T cells come from a donor, rather than the patient—citing lower manufacturing costs and a higher number of patients that could receive treatment. Leonard wasn’t able to provide an ETA for launching into the clinic, but the company says preclinical data will be available at a conference later this year. 

“If you're able to manufacture for 50 to 100 people at the same time, that just brings tremendous opportunities in terms of efficiency, cost of goods, improvements that we think can ultimately expand the use of these products,” said Leonard, adding that he believes the program can progress “very, very quickly.”