Intellia's CRISPR program that edits genes directly in patients shows durability in ATTR amyloidosis
The first in vivo CRISPR/Cas9 gene editing program has some new durability data showing sustained reduction of a toxic protein in ATTR amyloidosis at all four dose levels in a small 15-patient study.
Intellia Therapeutics presented the much-anticipated data for its Regeneron-collaborated NTLA-2001 Friday morning, adding to the initial Phase I results it first delivered almost a year ago to the day.
The Cambridge, MA, biotech’s shares $NTLA climbed nearly 6% before the opening bell Friday.
Intellia is now in talks with the FDA and other regulators about trial design for a potential pivotal study, the Jennifer Doudna-founded biotech said on an investor call Friday morning. The much-tracked single-dose program, which edits genes directly inside the body, is being investigated for two different manifestations of ATTR amyloidosis — polyneuropathy, where patients have peripheral nerve damage, and cardiomyopathy, where patients’ heart muscles don’t work well.
All results since last June have been in polyneuropathy, with Friday’s data drop showing sustained durability in the rare condition in which toxic protein accumulates in a patient’s organs.
Back in February, Intellia had said that at the highest dose level (1.0mg/kg), six patients had shown a 93% mean reduction in the toxic protein. In the new data, three of those patients reached the nine-month follow-up point and maintained that level of TTR reduction.
The mean reduction for the three patients at the second-highest dose (0.7mg/kg) was 86%. For the longest-tracked group, dose level two at 0.3mg/kg, the three patients had a mean reduction of 89%.
Part II of the study, which is ongoing, is testing a dose of 80mg, the fixed-dose equivalent of the highest dose group in Part I, the company said.
Headaches, infusion-related reactions, back pain, rash and nausea were the most frequent adverse events across all four dose levels, the biotech said. Eleven of the 15 patients reported a maximal adverse event of grade 1. The most serious adverse event, which Intellia said was “possibly related” to its treatment, was grade 3 vomiting in a patient with a medical history of gastroparesis.
“Based on the interim data shared today, we believe NTLA-2001’s potential to be a transformational treatment for patients with ATTR amyloidosis is becoming clearer. The safety, depth of serum TTR reduction and durability profile demonstrated thus far highlights its potential for halting and reversing the disease after a single dose,” said CEO and president John Leonard in a statement.
The company will complete enrollment for both the polyneuropathy and cardiomyopathy arms of the trial later this year and will present the first cardiomyopathy results by year’s end, Intellia said.
Intellia is trying to leapfrog Alnylam’s Onpattro and recently approved Amvuttra, as well as Ionis’ Tegsedi. Those are all RNA-targeting drugs, but require constant dosing compared to Intellia’s one-time therapy. Onpattro and Tegsedi have shown reduced mutant protein expression by about 80%.
Alnylam is pursuing label expansions of its Onpattro and Amvuttra in ATTR with cardiomyopathy, as well.