Akcea & Ionis Announce Initiation of NEURO-TTRansform Phase 3 Clinical Trial 


Akcea Therapeutics, Inc., a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. recently announced initiation of the NEURO-TTRansform Phase 3 clinical trial for AKCEA-TTR-LRx in patients with polyneuropathy caused by h856ereditary TTR amyloidosis, or hATTR amyloidosis.

“The initiation of the TTRransform Phase 3 program represents an expansion of our dedication and commitment to the ATTR community. The NEURO-TTRansform study is the first of two Phase 3 studies that we expect to initiate with AKCEA-TTR-LRx. Our Phase 1 data are encouraging and we are excited about the possibility of delivering a significant advancement for people living with hATTR amyloidosis,” said Damien McDevitt, PhD, Interim Chief Executive Officer at Akcea.

AKCEA-TTR-LRx is an antisense drug developed using Ionis’ proprietary LIgand Conjugated Antisense (LICA) technology platform and is designed to inhibit production of TTR. It was discovered by Ionis and is being co-developed by Ionis and Akcea. In a Phase 1 clinical trial, patients treated with AKCEA-TTR-LRx experienced reductions in TTR of up to 94%.

“The Phase 1 data of AKCEA-TTR-LRx are consistent with the clinical profile seen across our other LICA programs, highlighting the potential of LICA-engineered therapies to address both rare and more common diseases,” added Brett P. Monia, PhD, Chief Operating Officer at Ionis. “We remain dedicated to advancing this important clinical development program as rapidly as possible and are hopeful about the prospect of bringing a new safe and effective treatment to people living with the devastating symptoms of hATTR amyloidosis in the years ahead.”

NEURO-TTRansform is a global, open-label, randomized study evaluating the efficacy and safety of AKCEA-TTR-LRx in patients with polyneuropathy due to hATTR amyloidosis. The study will enroll 140 adult patients with stage 1 or stage 2 polyneuropathy and will be compared to the historical placebo arm from the TEGSEDI (inotersen) NEURO-TTR Phase 3 study that was completed in 2017. Of the total 140 participants, 20 patients will begin on TEGSEDI and move to AKCEA-TTR-LRx after week 35. The primary endpoint analysis will be completed at week 66 and all patients will be followed until week 85 when they will have the option to transition into the open label extension study.

The co-primary efficacy endpoints at week 66 are:

-Percent change from baseline in serum TTR concentration;

-Change from baseline in the modified Neuropathy Impairment Score +7 (mNIS+7), a measure of neuropathic disease progression; and

-Change from baseline in Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN).

There will be an interim analysis at week 35 where the co-primary efficacy endpoints are percent change from baseline in serum TTR concentration and change from baseline in mNIS+7. For more information on the NEURO-TTRansform study, please visit www.clinicaltrials.gov.

AKCEA-TTR-LRx is an antisense drug that uses Ionis’ advanced LIgand Conjugated Antisense, or LICA, technology. It was discovered by Ionis and is being co-developed by Ionis and Akcea. AKCEA-TTR-LRx inhibits the production of the transthyretin (TTR) protein at its source. AKCEA-TTR-LRx is in development to treat a broad population of patients with both hereditary and wild-type forms of transthyretin amyloidosis, or ATTR amyloidosis.

hATTR amyloidosis is a severe, progressive, and life-threatening disease caused by the abnormal formation of the TTR protein and aggregation of TTR amyloid deposits in various tissues and organs throughout the body, including in peripheral nerves, the heart and intestinal tract. The progressive accumulation of TTR amyloid deposits in these organs often leads to intractable peripheral sensorimotor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations. hATTR amyloidosis causes significant morbidity and progressive decline in quality of life, severely impacting activities of daily living. The disease often progresses rapidly and can lead to premature death. The median survival is 4.7 years following diagnosis. Additional information on hATTR amyloidosis, including a full list of organizations supporting the hATTR amyloidosis community worldwide, is available at www.hattrchangethecourse.com or by visiting www.hATTRGuide.com.

As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for children and adults with spinal muscular atrophy as well as the world’s first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to treat a broad range of diseases including cardiovascular diseases, neurological diseases, infectious diseases, pulmonary diseases and cancer. For more information, visit www.ionispharma.com.

Akcea Therapeutics, Inc., a majority-owned affiliate of Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), is a biopharmaceutical company focused on developing and commercializing drugs to treat patients with serious and rare diseases. Akcea is commercializing TEGSEDI (inotersen) and WAYLIVRA (volanesorsen), as well as advancing a mature pipeline of novel drugs, including AKCEA-APO(a)-LRx, AKCEA-ANGPTL3-LRx, AKCEA-APOCIII-LRx, and AKCEA-TTR-LRx, with the potential to treat multiple diseases. All six drugs were discovered by Ionis, a leader in antisense therapeutics, and are based on Ionis’ proprietary antisense technology. TEGSEDI is approved in the US, EU, and Canada. WAYLIVRA is approved in the E.U. and is currently in Phase 3 clinical development for the treatment of people with familial partial lipodystrophy, or FPL. Akcea is building the infrastructure to commercialize its drugs globally. Akcea is a global company headquartered in Boston, MA. For more information, visit  www.akceatx.com.

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