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Ionis Collaborates with AstraZeneca to Develop and Commercialize Eplontersen for ATTR

December 7, 2021

Ionis Pharmaceuticals has entered into a strategic collaboration agreement with AstraZeneca to develop and commercialize eplontersen, Ionis’ investigational antisense medicine for the treatment of transthyretin amyloidosis.

Photo: Brett Monia, CEO of Ionis

Under the terms of the agreement, Ionis will receive a $200 million upfront payment, up to $485 million in development and approval milestones, and up to $2.9 billion in sales-related milestone payments. The collaboration includes territory-specific development, commercial and medical affairs cost-sharing provisions. Ionis is also eligible to earn royalties in the range of low double-digit to mid-20s percentage depending on region.

“We believe that bringing together Ionis’ industry-leading experience in RNA-targeted therapeutics and deep knowledge of the TTR amyloidosis market with AstraZeneca’s global scale and leadership in cardiovascular drug development and commercialization will enable faster and deeper market penetration for the benefit of patients,” said Brett Monia, CEO of Ionis. “In addition to being the best strategy to maximize patient and shareholder value for eplontersen, this agreement also represents a key step in bolstering our commercial organization as we prepare to launch multiple products.”

Transthyretin amyloidosis (ATTR) is a systemic, progressive and fatal disease in which patients experience multiple overlapping clinical manifestations caused by the inappropriate formation and aggregation of TTR amyloid deposits in various tissues and organs, including peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone marrow. The progressive accumulation of TTR amyloid deposits in these tissues and organs leads to organ failure and eventually death.

Polyneuropathy due to hereditary ATTR (hATTR) is caused by the accumulation of misfolded mutated TTR protein in the peripheral nerves. Patients with polyneuropathy due to hATTR experience ongoing debilitating nerve damage throughout their body resulting in the progressive loss of motor functions, such as walking. These patients also accumulate TTR in other major organs, which progressively compromise their function and eventually leading to death within five to fifteen years of disease onset.

ATTR cardiomyopathy is caused by the accumulation of misfolded TTR protein in the cardiac muscle. Patients experience ongoing debilitating heart damage resulting in progressive heart failure, which results in death within three to five years from disease onset. ATTR cardiomyopathy includes both the genetic and wild-type form of the disease. Worldwide, there are an estimated 300,000 – 500,0001,2 patients with ATTR.

Eplontersen, formerly known as IONIS-TTR-LRx, is designed to reduce the production of transthyretin, or TTR protein, to treat all types of ATTR. Ionis is currently evaluating eplontersen through its CARDIO-TTRansform phase 3 study for the treatment of patients with hereditary and wild-type cardiomyopathy (ATTR-CM) and its NEURO-TTRansform phase 3 study for the treatment of patients with hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN).

As part of their agreement, Ionis and AstraZeneca will develop a global strategy for developing, manufacturing and commercializing eplontersen. Ionis will continue to lead the conduct of the global phase 3 clinical trials in patients with (hATTR) with polyneuropathy (NEURO-TTRansform) and cardiomyopathy (CARDIO-TTRansform).

Ionis will manufacture and supply eplontersen for the ongoing clinical trials and process qualifications. AstraZeneca will be responsible for commercial supply, with transition timing to be agreed by both companies. Ionis and AstraZeneca will have shared responsibility for medical affairs and commercial activities in the U.S. AstraZeneca will have an exclusive license for eplontersen outside the United States except certain countries in Latin America.

Hereditary ATTR amyloidosis (hATTR) with polyneuropathy is expected to be the first indication for which the companies will seek regulatory approval for eplontersen, with the potential to file a new drug application with the U.S. Food and Drug Administration by the end of 2022.

Author: Rare Daily Staff

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