Intellia Therapeutics and Regeneron Pharmaceuticals announced early-stage data suggesting that a single dose of the experimental CRISPR/Cas9-based therapy NTLA-2001 may be able to halt and reverse the complications of hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), a disease characterised by progressive build-up of misfolded transthyretin (TTR) protein in tissue. "These are the first ever clinical data suggesting that we can precisely edit target cells within the body to treat genetic disease with a single intravenous infusion of CRISPR," remarked John Leonard, CEO at Intellia, which saw shares jump as much as 54% on the news.
According to interim results presented at the Peripheral Nerve Society (PNS) annual meeting and published in the NEJM, the three patients administered the highest dose of NTLA-2001 achieved a mean reduction of 87% in serum TTR concentration at day 28, including one subject with a 96% decline. The companies noted that the current standard of care for ATTRv-PN, which requires chronic treatment, typically yields reductions of approximately 80%. Meanwhile, the three patients in the lower-dose group saw serum TTR levels go down by a mean 52% at day 28.
Intellia and Regeneron noted that the two dose levels of NTLA-2001 so far tested have been generally well tolerated by all six patients included in the interim analysis, with no serious adverse events and no liver findings by day 28. The companies plan to evaluate whether a higher dose could produce deeper reduction in disease-causing protein levels, allowing for potentially more meaningful clinical benefit.
NTLA-2001, which is given by intravenous infusion, is the first CRISPR/Cas9-based therapy to be administered systemically, according to Intellia and Regeneron. The therapy is designed to inactivate the TTR gene in liver cells to prevent the production of misfolded TTR protein. Leonard said "solving the challenge of targeted delivery of CRISPR/Cas9 to the liver, as we have with NTLA-2001, also unlocks the door to treating a wide array of other genetic diseases with our modular platform."
Intellia and Regeneron said that they expect to begin a single-dose expansion cohort in Part 2 of the Phase I trial later this year, after which the plan is to move to pivotal studies in both polyneuropathy and cardiomyopathy manifestations of ATTR amyloidosis. Regeneron first partnered with Intellia in 2016 to advance CRISPR/Cas9 gene-editing technology for in vivo therapeutic development, with the collaboration expanded last year.
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