Benefits of eplontersen continue for more than 1.5 years: Trial data

Treatment found to safely and effectively ease symptoms, improve life quality

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Eplontersen continues to safely and effectively ease symptoms and improve quality of life for people with familial amyloid polyneuropathy (FAP) who have been on the treatment for more than 1.5 years in the Phase 3 NEURO-TTRansform clinical trial.

That’s according to top-line, 85-week results announced by Ionis Pharmaceuticals, which is developing eplontersen alongside AstraZeneca.

“These positive findings further strengthen eplontersen’s efficacy and safety profile, underscoring its potential to be an important, differentiated advancement for patients with this progressive, debilitating and fatal disease,” Eugene Schneider, MD, executive vice president and chief clinical development officer at Ionis, said in a company press release.

The companies plan to present the new data at an upcoming medical meeting.

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Eplontersen for 1 year found to safely ease symptoms in FAP adults

Eplontersen designed to reduce production of transthyretin protein

In FAP, also known as hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), symptoms are driven by the toxic buildup of transthyretin protein in the body’s tissues.

Eplontersen is designed to reduce production of this protein. The experimental therapy works via a similar mechanism to Ionis’ approved FAP therapy Tegsedi (inotersen), but it’s designed to be better at getting into the liver where most transthyretin protein is made.

Both therapies can be self-administered by patients through under-the-skin injections, but while Tegsedi is given once a week, the second-generation therapy is administered once a month.

The U.S. Food and Drug Administration is currently reviewing an application from Ionis seeking eplontersen’s approval, with a decision expected in late December. Ionis and AstraZeneca plan to submit similar applications to regulatory agencies in Europe and other parts of the world.

“ATTRv-PN continues to be an underserved patient population and we look forward to working with regulatory authorities to bring this important new, self-administered treatment to patients,” Schneider said.

Ionis’ application is based on data from the global NEURO-TTRansform trial (NCT04136184), which enrolled 168 adults with FAP. Participants were first treated with either eplontersen or Tegsedi for 37 weeks (about eight months), after which all were given eplontersen for 48 weeks (about 11 months), totaling 85 weeks (about 19 months).

Earlier this year, Ionis announced top-line, 15-month trial data that compared findings from eplontersen-treated patients with those of an external placebo group from a prior Tegsedi Phase 2/3 trial (NCT01737398).

The data showed that eplontersen led to a significantly slower nerve damage progression, as measured by the modified Neuropathy Impairment Score +7 (mNIS+7), as well as improvements in quality of life, as assessed with the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN).

This contrasted with the trends in the external placebo group, which showed a worsening of nerve damage and life quality over time, which is expected without treatment in a progressive disorder like FAP.

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Eplontersen led to improvement in symptom severity, life quality over 85 weeks

The new data — covering up to 85 weeks, or a little more than 1.5 years, of eplontersen treatment — showed that average scores on the mNIS+7 were 2.9 points lower than at the study’s start, reflecting a slight improvement in symptom severity. Scores on the Norfolk QoL-DN were also lower than at the study’s start, by an average of 6.2 points, indicating better life quality.

“A substantial number of eplontersen-treated patients showed improvement in [nerve damage] impairment and quality of life through 19 months of treatment,” Schneider said.

Also, the significantly lower blood transthyretin levels observed after 15 months of treatment relative to the external placebo group were maintained with longer-term treatment. Levels were on average 81.8% lower after 85 weeks than at the start of the trial.

Longer-term safety data were consistent with previously reported findings. No serious side effects associated with eplontersen were reported. Three patients given the experimental medication have died, all due to complications associated with FAP and unrelated to the therapy.

Participants completing the NEURO-TTRansform trial will have the option to either enroll in an open-label extension study (NCT05071300), in which they will continue on eplontersen for up to 3.5 years, or enter a 20-week post-treatment evaluation period.

Ionis is also sponsoring a Phase 3 trial called CARDIO-TTRansform (NCT04136171) to test eplontersen against a placebo in up to 1,400 people with transthyretin-mediated amyloid cardiomyopathy, where transthyretin buildup causes damage in the heart. That study may still be recruiting participants at sites in the U.S., Canada, Brazil, Argentina, Israel, Australia, Japan, and several countries in Europe.