Wainua shows similar benefits for men, women with hATTR-PN in trial
Analysis finds slowed nerve damage, better quality of life
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Treatment with Wainua (eplontersen) was associated with slower disease progression and improved quality of life in both men and women with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN).
That’s according to an exploratory analysis of data from the Phase 3 NEURO-TTRansform clinical trial (NCT04136184), whose top-line results supported the treatment’s approval. The findings support Wainua “as an effective treatment for hATTR-PN regardless of sex,” the researchers wrote.
Wainua designed to lower toxic TTR buildup
The results were detailed in the study “Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy: An Exploratory Analysis of Treatment Effect in Male and Female Patients,” published in Muscle & Nerve.
The NEURO-TTRansform trial was sponsored by Ionis Pharmaceuticals, and this analysis was supported by AstraZeneca, which holds exclusive Wainua commercialization rights in countries outside the U.S. and markets the therapy in the U.S. with Ionis Pharmaceuticals.
hATTR-PN, also known as familial amyloid polyneuropathy or ATTRv-PN, is caused by mutations in the TTR gene, resulting in the production of misfolded transthyretin (TTR) protein that forms toxic protein clumps called amyloid deposits. These deposits can build up in the peripheral nerves, which are found outside the brain and spinal cord, and may also affect the heart and other organs.
Wainua contains a piece of genetic material that reduces TTR production, which is expected to lower the buildup of amyloid deposits and slow hATTR-PN progression. The treatment is given as an under-the-skin (subcutaneous) injection once a month and can be administered by patients or caregivers at home.
Previous results from the NEURO-TTRansform trial, which included 144 adults with hATTR-PN at a Coutinho stage 1 or 2, showed that Wainua slowed disease progression and improved patients’ quality of life regardless of hATTR-PN-causing mutations and nutritional status. The treatment was also shown to reduce autonomic symptoms, which are caused by damage to nerves that control involuntary bodily functions.
Data from Wainua-treated patients in NEURO-TTRansform were compared with those from an external group of hATTR-PN patients given a placebo in a previous Phase 2/3 trial (NCT01737398). Results from that study supported the approval of Tegsedi (inotersen), another Ionis-developed therapy for hATTR-PN that was discontinued in 2024.
Analysis compares treatment effects by sex
Now, to better understand Wainua’s effects across sexes, a research team compared data from the 100 men and 44 women given Wainua in NEURO-TTRansform with data from 41 men and 19 women given a placebo in the prior Phase 2/3 trial.
At the start of either study, or baseline, the participants’ mean age ranged from about 52 to 59 years in men and about 56 to 60 years in women. In general, men were younger, had a longer disease duration since the onset of neurological symptoms, and a higher prevalence of hereditary ATTR cardiomyopathy (hATTR-CM), a related condition in which TTR deposits build up in the heart and can cause damage.
Among Wainua-treated patients, early-onset hATTR-PN related to the Val30Met mutation, with symptoms before age 50, was more common in men. Late-onset Val30Met, with symptoms at age 50 or older, had a similar prevalence in men and women.
About 20% of Wainua-treated men and women had a mixed profile involving both hATTR-PN and hATTR-CM.
After 65 weeks, or about 1.3 years, of Wainua treatment, blood TTR levels decreased by more than 80% in men and women. In the external placebo group, the decrease was below 14% for both sexes.
At baseline, most patients had polyneuropathy disability scores of I or II, meaning they could walk without assistance, although some had walking difficulties. Men and women treated with Wainua generally maintained less severe disability scores than those in the placebo group, who experienced disability progression.
Wainua effects similar in men and women
Neurological impairment, assessed by the modified Neuropathy Impairment Score plus 7, was maintained in men and women treated with Wainua, but worsened in those in the external placebo group.
Patients’ quality of life, measured using the Norfolk Quality of Life-Diabetic Neuropathy questionnaire, improved in Wainua-treated men and women but worsened in those in the placebo group.
Results also favored Wainua in both sexes for reducing the severity and progression of neuropathy symptoms, as assessed by the Neuropathy Symptom and Change score, and for improving quality of life on the 36-Item Short-Form Health Survey.
Nutritional status, assessed using the modified body mass index, a measure that combines weight, height, and blood protein levels, was maintained with Wainua in both sexes, but worsened in the placebo group.
Overall, for the outcomes formally tested, there were no significant differences in Wainua’s treatment effect versus placebo between men and women. Wainua effects were also similar in male and female patients with cardiomyopathy.
These findings show that Wainua “can lead to substantial decreases in percentage [blood] TTR levels, arrest neuropathy impairment, and improve quality of life, regardless of patient sex,” the researchers wrote.
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