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Abstract Details

Eplontersen in Hereditary ATTR-polyneuropathy: Week 66 Final Analysis of the Phase 3 NEURO-TTRansform Study
General Neurology
ES1 - Emerging Science 1 (11:57 AM-12:03 PM)
008

ATTRv-PN is a rare, progressive, and debilitating disease caused by accumulation of amyloid fibrils composed of transthyretin (TTR) protein in multiple organ systems. Eplontersen, a ligand-conjugated antisense oligonucleotide that inhibits TTR protein synthesis, is being assessed in the NEURO-TTRansform study. Previously reported topline statistics established that the coprimary endpoints and key secondary endpoint were met at the prespecified Week 35 interim analysis. Eplontersen treatment resulted in significant reductions in serum TTR concentration and neuropathy impairment (modified Neuropathy Impairment Score +7 [mNIS+7]), and improved quality of life (Norfolk Quality of Life-Diabetic Neuropathy score [Norfolk QoL-DN]), compared with external placebo (from the NEURO-TTR study [NCT01737398]). Eplontersen treatment also demonstrated an acceptable safety and tolerability profile.

To evaluate the final efficacy and safety analysis of eplontersen at Week 66 in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, open-label NEURO-TTRansform study (NCT04136184). 

NEURO-TTRansform enrolled 168 adults with ATTRv-PN, defined by Coutinho Stage 1?2, a documented TTR sequence variant, and signs/symptoms consistent with polyneuropathy (Neuropathy Impairment Score ≥10 and ≤130). Patients were assigned 6:1 to eplontersen 45 mg subcutaneously every 4 weeks (n=144) or inotersen 300 mg once weekly (n=24) until the prespecified Week 35 interim analysis, after which all patients received eplontersen 45 mg subcutaneously every 4 weeks. All patients who received eplontersen were compared with an external placebo group from the NEURO-TTR study at Week 66. Coprimary efficacy assessments at Week 66 included serum TTR concentration, mNIS+7, and the Norfolk QoL-DN score. Safety and tolerability were also assessed.

Full results from the efficacy and safety analysis at Week 66 and Week 35 will be presented.

Results from the final analysis at Week 66 will provide detailed longer-term data on the efficacy and safety of eplontersen in patients with Stage 1 or 2 ATTRv-PN.

Authors/Disclosures
Sami L. Khella, MD, FAAN (Presbyterian Med Ctr/Dept of Neuro)
PRESENTER
Dr. Khella has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ionis. Dr. Khella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. Dr. Khella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Khella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Khella has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eidos.
Wilson Marques, Jr., MD (School of Medicine of Ribeirao Preto) Dr. Marques has nothing to disclose.
No disclosure on file
Chi-Chao Chao (Department of Neurology, National Taiwan Univ) Chi-Chao Chao has nothing to disclose.
Fatma Yesim Parman, MD (Istanbul Üniversitesi Tip Fakültesi) Dr. Parman has nothing to disclose.
Marcondes C. Franca, Jr., MD Dr. Franca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Franca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC. Dr. Franca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Franca has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Franca has received research support from FARA.
Yuh-Cherng Guo Yuh-Cherng Guo has nothing to disclose.
No disclosure on file
Long-Sun Ro, MD, PhD (Chang Gung Memorial Hospital) Dr. Ro has nothing to disclose.
Cristian Calandra, MD (Merck Serono Argentina) Dr. Calandra has nothing to disclose.
Pedro A. Kowacs, MD, FAAN (Private Office) Dr. Kowacs has nothing to disclose.
John L. Berk John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam Pharmaceuticals. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis Pharmaceuticals. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca/IONIS. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eidos/BridgBio. John L. Berk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Intellia Therapeutics. John L. Berk has received research support from Alnylam . John L. Berk has received research support from Ionis. John L. Berk has received research support from Eidos/Bridgbio.
Laura Piera Obici (Fondazione IRCCS Policlinico San Matteo) No disclosure on file
Fabio Adrian Barroso, MD Fabio Adrian Barroso, MD has nothing to disclose.
No disclosure on file
Isabel Conceicao (Hospital de Santa Maria) Isabel Conceicao has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Isabel Conceicao has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sobi.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Eugene Schneider, MD (Ionis Pharmaceuticals, Inc) Dr. Schneider has received personal compensation for serving as an employee of ionis pharmaceuticals.
Nicholas Viney Nicholas Viney has received personal compensation for serving as an employee of Ionis Pharmaceuticals Inc.. Nicholas Viney has stock in Ionis Pharmaceuticals. Nicholas Viney has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
P. James B. Dyck, MD, FAAN (Mayo Clinic) Dr. Dyck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea/Ionis.
Marcia Waddington Cruz, MD (Hospital Universitario) Dr. Waddington Cruz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Waddington Cruz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Waddington Cruz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca. Dr. Waddington Cruz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC. Dr. Waddington Cruz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Waddington Cruz has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sobi. Dr. Waddington Cruz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Waddington Cruz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. Dr. Waddington Cruz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC. Dr. Waddington Cruz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NovoNordisk.
Teresa Coelho, MD (Unidate Clinica de Paramoloidose Hospital) Dr. Coelho has nothing to disclose.