Ionis Pharmaceuticals and its affiliate Akcea Therapeutics have launched a Phase III clinical trial of AKCEA-TTR-L to treat polyneuropathy in patients with hereditary TTR (hATTR) amyloidosis.
hATTR amyloidosis is a progressive disease that develops due to the abnormal formation of the transthyretin (TTR) protein and accumulation of TTR amyloid deposits.
Based on Ionis’ ligand conjugated antisense (LICA) technology, AKCEA-TTR-L is an antisense drug designed to block the generation of the TTR protein at its source.
The drug is being jointly developed by Ionis and Akcea to treat patients with hereditary and wild-type forms of transthyretin (ATTR) amyloidosis.
Named NEURO-TTRansform, the Phase III trial will assess the safety and efficacy of AKCEA-TTR-L in 140 adults with stage 1 or stage 2 polyneuropathy caused by hATTR amyloidosis.
The global, open-label, randomised trial will compare the drug to the placebo arm from the NEURO-TTR Phase III study of Tegsedi (inotersen), which was completed in 2017.
Of the total patients, 20 will initially receive Tegsedi and switch to AKCEA-TTR-L after week 35.
The co-primary efficacy endpoints are the change in serum TTR concentration, the modified Neuropathy Impairment Score +7, which measures neuropathic disease progression, and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy from baseline to week 66.
NEURO-TTRansform involves follow-up until week 85, when the patients can opt to participate in the open-label extension study.
When evaluated in a Phase I study, AKCEA-TTR-L demonstrated a decrease of up to 94% in TTR.
Ionis Pharmaceuticals chief operating officer Brett Monia said: “The Phase I data of AKCEA-TTR-L are consistent with the clinical profile seen across our other LICA programmes, highlighting the potential of LICA-engineered therapies to address both rare and more common diseases.
“We remain dedicated to advancing this important clinical development programme as rapidly as possible and are hopeful about the prospect of bringing a new safe and effective treatment to people living with the devastating symptoms of hATTR amyloidosis in the years ahead.”
The company also reported plans to study the drug in another Phase III trial.