Wainua slows FAP progression in key patient groups: Phase 3 trial

Benefits seen regardless of nutritional status, sex, or a common mutation

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Wainua (eplontersen) is able to slow disease progression and improve life quality for people with familial amyloid polyneuropathy (FAP) regardless of nutritional status, sex, or certain genetic factors.

That’s according to new subgroup analyses from the Phase 3 NEURO-TTRansform clinical trial (NCT04136184), whose top-line data supported Wainua’s U.S. approval for adults with FAP in December.

Findings were discussed across several presentations at the International Symposium on Amyloidosis, held May 26-30 in Rochester, Minnesota.

AstraZeneca and Ionis, the therapy’s developers, are seeking regulatory approvals for Wainua in Europe and other regions, according to a company press release.

“Our data … showcases the leadership and dedication of AstraZeneca and our partner Ionis in developing best-in-class treatment options through greater understanding of treatment effects in [FAP] and patient characteristics from our Phase 3 NEURO-TTRansform study,” Sarah Walters, vice president of U.S. cardiovascular, renal, and metabolic diseases at AstraZeneca, said in an emailed statement to FAP News Today.

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Amyloidosis is a group of conditions characterized by toxic protein clumps, called amyloid fibrils, that accumulate in tissues, leading to organ damage. In FAP, an inherited form of amyloidosis, toxic aggregates of the transthyretin protein mainly build in the nerves outside the brain and spinal cord, leading to nerve damage and other disease symptoms.

Wainua, self-administered as an under-the-skin injection once a month, is designed to reduce transthyretin production, thereby preventing its toxic accumulation and slowing FAP progression.

In NEURO-TTRansform, 144 adults with stage 1 or 2 FAP were treated with Wainua. Trial results showed that a little more than one year of treatment significantly slowed nerve damage progression and improved life quality relative to an external placebo group from a previous FAP trial. Treatment benefits were sustained for more than 1.5 years.

Newly presented findings concerned subgroup analyses of NEURO-TTRansform data.

In a poster titled “Neuropathy Impairment and Nutritional Status with Eplontersen in Patients with Hereditary Transthyretin-Mediated Amyloidosis (abstract 174),” Jonas Wixner, MD, PhD, with Umeå University in Sweden, presented results of an analysis looking at the link between nutritional status and disease progression with Wainua’s use.

Weight loss is commonly observed in FAP patients. Body mass index (BMI), a ratio of person’s height and weight that serves as a proxy of body fat, was used to assess participants’ nutritional status.

In general, BMI tended to increase, or improve, with Wainua while it declined in the historical placebo group. While 42% of patients in that placebo group showed a more than a 10% drop in BMI, a similar decline was reported in 12% of patients on Wainua.

Gains in body mass index, life quality reported across patients

Importantly, Wainua’s benefits in terms of disease progression and life quality consistently were superior to those of a placebo across all categories evaluating BMI change, including patients who gained weight, lost weight, or remained relatively stable.

“Regardless of change in nutritional status, [Wainua] halted progression of [nerve damage] impairment and improved [life quality],” the researchers wrote in the poster, noting that findings indicate that even those with a worsening nutritional status might benefit from the therapy.

In the poster “Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy: An Exploratory Analysis in Patients with the V30M TTR Variant and Early-Onset or Late-Onset Disease,” Julian D. Gillmore, MD, PhD, with the National Amyloidosis Centre at University College London, discussed findings from a subgroup of trial participants carrying Val30Met — the most common FAP-causing mutation.

The analysis included 54 patients with early-onset disease, where symptoms start before age 50, and 31 with late-onset disease (at 50 years and older), who were compared with similar patients in the historical placebo group.

Disease progression tended to be slower with Wainua relative to placebo in both early- and late-onset patients with the Val30Met mutation. Similarly, life quality measures favored use of the treatment.

Wainua also associated with a better nutritional status for both groups, as indicated by a relatively stable BMI in Wainua-treated patients compared with a marked decline in the placebo group.

Márcia Waddington Cruz, MD, PhD, with the Brazilian Amyloid National Referral Center (CEPARM) and Federal University of Rio de Janeiro, explored Wainua’s effects by patients’ sex in the poster “Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy: An Exploratory Analysis of Treatment Effect in Male and Female Patients.”

Among NEURO-TTRansform participants, 100 were men and 44 were women. The Val30Met mutation with early-onset disease was more common in men than women.

Again, Wainua was found to be superior to a placebo at slowing nerve damage progression and improving life quality regardless of sex, with a similar degree of improvements seen in both men and women.

“We are grateful to the patients, families and investigators participating in our trials so that together we can improve the standard of care and address gaps in amyloidosis,” Walters said.