New study tests nucresiran’s potential to slow nerve damage
Phase 3 trial studying treatment for hATTR-PN, results expected in 2028
Alnylam Pharmaceuticals has launched a Phase 3 clinical trial testing its experimental treatment nucresiran in adults with familial amyloid polyneuropathy (FAP), also known as hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN). Top-line results are expected in 2028.
This update came in the company’s latest pipeline and financial report, announced in a press release.
As part of the trial, called TRITON-PN (NCT07223203), up to 125 participants will receive either nucresiran — given every six months as an under-the-skin (subcutaneous) injection — or Alnylam’s Amvuttra (vutrisiran), which is approved in the U.S. and the European Union to treat adults with FAP. Recruiting sites have not yet been listed.
Trial will track changes in nerve function over time
The main goal is to measure changes in the Modified Neuropathy Impairment Score +7, a tool that assesses the level of neurological impairment, after nine months. The results will be compared with data from the placebo group in APOLLO (NCT01960348), the Phase 3 trial that supported approval of Alnylam’s Onpattro (patisiran) for FAP.
“In addition to our commercial success, we also made significant progress advancing late-, mid-, and early-stage programs,” including “the TRITON-PN study for nucresiran in hATTR-PN now initiating,” Yvonne Greenstreet, MD, CEO of Alnylam, said in a press release reporting on the company’s latest financial results.
FAP is a hereditary form of ATTR amyloidosis, a group of conditions marked by the production of a faulty TTR protein that can form toxic clumps and damage tissues. The condition results from mutations in the TTR gene, which encodes the TTR protein, and commonly leads to nerve damage outside the brain and spinal cord, causing neurological symptoms.
Like Onpattro and its successor, Amvuttra, nucresiran works by “silencing” the genetic material that serves as the template to produce the TTR protein. By reducing TTR protein production, nucresiran is expected to slow disease progression in FAP and other forms of ATTR amyloidosis, hereditary or not.
However, unlike Onpattro, which is given by infusion every three weeks, or Amvuttra, given as a subcutaneous injection every three months, nucresiran is expected to result in greater TTR reductions with only two subcutaneous injections per year.
Phase 1 data suggest therapy may offer long-lasting effects
In a now-completed Phase 1 clinical trial (NCT05661916) involving 48 healthy adults, a single nucresiran injection at a dose of 300 mg or higher reduced blood levels of TTR by an average of at least 90% for up to one year compared with a placebo. The therapy was also safe and generally well tolerated.
The TRITON-PN study will recruit adults, ages 18-85, with a diagnosis of FAP and a documented disease-causing TTR mutation. Participants will be randomly assigned, in a 4-to-1 ratio, to receive either the 300 mg dose of nucresiran or the approved dose of Amvuttra (25 mg).
Those who complete this part may roll over into an extension portion in which all participants receive nucresiran.
In addition to the main goal, researchers will also watch for changes in the Norfolk Quality of Life-Diabetic Neuropathy score — a patient-reported measure of quality of life — blood TTR levels, and modified body mass index — a measure of nutritional status — after nine and 18 months.
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