FAP treatment Wainua reduces autonomic symptoms: Trial data

Phase 3 NEURO-TTRansform results supported therapy's approval in 2023

Katherine Poinsatte, PhD avatar

by Katherine Poinsatte, PhD |

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People with familial amyloid polyneuropathy (FAP) have fewer autonomic symptoms caused by damage to the nerves that control involuntary bodily functions after more than 1.5 years of treatment with Wainua (eplontersen) compared with a placebo.

That’s according to a new secondary analysis from the Phase 3 NEURO-TTRansform clinical trial (NCT04136184), the top-line data of which supported Wainua’s U.S. approval for adults with FAP in 2023.

“[Wainua] demonstrated benefit across multiple measures of autonomic impairment known to progress rapidly and negatively impact [quality of life] without treatment,” the researchers wrote. The study, “Effects of eplontersen on symptoms of autonomic neuropathy in hereditary transthyretin-mediated amyloidosis: secondary analysis from the NEURO-TTRansform trial,” was published in Amyloid.  Wainua is marketed by Ionis Pharmaceuticals and AstraZeneca. Some of the study’s authors are employed by these companies.

Amyloidosis is a group of conditions wherein toxic protein clumps, called amyloid fibrils, accumulate in tissues, causing organ damage. FAP patients have an inherited form of amyloidosis, where toxic clumps of the transthyretin protein build up in the nerves outside the brain and spinal cord.

This nerve damage causes an array of symptoms, including peripheral neuropathy, which results from peripheral nerve damage, and heart problems. Most patients also have autonomic symptoms, including low blood pressure upon standing, and gastrointestinal problems like constipation and incontinence.

“Autonomic symptoms may emerge at or soon after disease onset, and contribute strongly to disease burden and impaired health-related quality of life,” the researchers wrote.

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Effect on autonomic symptoms of FAP

Wainua, which is self-administered as a monthly injection under the skin, is designed to reduce transthyretin production, preventing its toxic buildup and slowing the disease’s progression.

In NEURO-TTRansform, 144 adults with stage 1 or 2 FAP were treated with Wainua and more than a year of treatment was found to improve quality of life and significantly slow nerve damage progression compared with an external placebo group from a previous FAP trial. These benefits were sustained for more than 1.5 years.

Here, a secondary analysis of NEURO-TTRansform data from 141 patients treated with Wainua and 59 patients from the external control group was conducted to determine if the treatment reduced autonomic symptoms.

FAP patients treated with Wainua showed consistent trends towards improvement in their total neuropathy symptoms relative to the external placebo group, which showed little or no improvement, or marked worsening up to week 66 (15 months).

When the researchers examined the patient responses specifically related to individual autonomic neuropathy symptoms, particularly urinary and gastrointestinal incontinence, they found improvements for Wainua-treated patients up to week 85, or almost 20 months.

Poor nutritional status is known to negatively impact survival in FAP patients. The modified body mass index (mBMI), an assessment of body fat that also takes into account blood levels of the protein albumin, remained stable at week 85 in patients treated with Wainua. The external placebo group had marked worsening in mBMI at both week 35 and 65, however. Treated participants also saw improvements in body weight.

“Longer-term assessment from the open-label extension to NEURO-TTRansform will determine whether reported improvements in autonomic function are sustained,” the researchers wrote.