AstraZeneca gets rights to market eplontersen across Latin America

Potential once-monthly FAP treatment, similar to Tegsedi, under FDA review

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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AstraZeneca has added Latin America to the list of regions in which it has exclusive commercialization rights for eplontersen, an investigational therapy being reviewed for approval by the U.S. Food and Drug Administration (FDA) to treat familial amyloid polyneuropathy (FAP).

Eplontersen’s original developer, Ionis Pharmaceuticals, teamed with AstraZeneca in 2021 to continue its development, granting AstraZeneca exclusive marketing rights in all countries outside the U.S., except for certain ones in Latin America.

Should eplontersen by approved in the U.S., it will be jointly commercialized there by the two companies. An FDA decision is expected on or before Dec. 22.

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For rights in Latin America, AstraZeneca has paid Ionis $20 million, with the possibility of up to $3.6 billion, partly based on the attainment of certain milestones. Ionis also is eligible for royalties on eplontersen sales in these countries, should it earn regulatory approval.

“With FDA review of eplontersen for [FAP] already underway and plans to file for regulatory approval in the [European Union] and other countries later this year, today’s agreement underscores our shared commitment to ensuring that this much needed treatment is made available to patients around the world,” Brett P. Monia, PhD, CEO of Ionis, said in a company press release.

FAP is a hereditary form of transthyretin amyloidosis (ATTR), an umbrella term for conditions in which the transthyretin protein forms toxic clumps that accumulate in cells.

The peripheral nerves that send signals between the brain and the rest of the body primarily are affected in people with FAP, leading to characteristic disease symptoms of nerve damage, or neuropathy.

Eplontersen works to reduce production of transthyretin to prevent it from forming toxic clumps. Its mechanism of action is similar to Tegsedi (inotersen), Ionis’ approved FAP therapy. But is designed to be better at reaching the liver, where most of the body’s transthyretin is made.

Both are under-the-skin (subcutaneous) injection therapies administered at home, but eplontersen requires less frequent dosing: once a month versus once each week for Tegsedi.

Ionis’ FDA application is supported by data from the global Phase 3 NEURO-TTRansform trial (NCT04136184), which evaluated the safety and effectiveness of eplontersen in 168 adults, ages 18 to 82, with stage 1 or 2 FAP.

Participants randomly were assigned to treatment with either eplontersen or Tegsedi for about eight months, after which all received eplontersen for roughly 11 more months — totaling a bit more than 1.5 years of treatment.

Top-line data, collected after about 15 months, showed that eplontersen led to statistically significant and clinically meaningful reductions in neuropathy symptoms and gains in life quality compared with an external placebo group — people given a placebo in a previous Phase 2/3 trial (NCT01737398) of Tegsedi.

Additional analyses indicated that eplontersen’s benefits were sustained for more than 1.5 years, with transthyretin levels an average of 81.8% lower at 85 weeks of treatment relative to the study’s start.

The treatment also was generally safe and well tolerated, with no serious side effects associated with eplontersen’s use.

“The positive clinical results from our Phase 3 NEURO-TTRansform study, combined with eplontersen’s self-administration profile, reinforce eplontersen’s potential to be an important and differentiated new treatment option for patients with ATTR,” Monia said.

Patients who complete the NEURO-TTRansform trial may choose to continue with eplontersen for up to 3.5 more years in an open-label extension study (NCT05071300) assessing its long-term safety and tolerability, or they will enter a 20-week post-treatment evaluation period.

Eplontersen also is being evaluated in the Phase 3 CARDIO-TTRansform trial (NCT04136171) as a potential treatment of transthyretin-mediated amyloid cardiomyopathy. In this form of ATTR transthyretin mainly accumulates in the heart, leading to heart failure. The study still may be recruiting up to 1,400 patients, ages 18 to 90, at sites worldwide.