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1. Switching from inotersen to eplontersen in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: analysis from NEURO-TTRansform

Author

Conceição, Isabel, Berk, John L., Weiler, Markus, Kowacs, Pedro A., Dasgupta, Noel R., Khella, Sami, Chao, Chi-Chao, Attarian, Shahram, Kwoh, T. Jesse, Jung, Shiangtung W., Chen, Jersey, Viney, Nicholas J., Yu, Rosie Z., Gertz, Morie, Masri, Ahmad, Cruz, Márcia Waddington, and Coelho, Teresa

Published
2024
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5. Design and Rationale of the Global Phase 3 NEURO-TTRansform Study of Antisense Oligonucleotide AKCEA-TTR-LRx (ION-682884-CS3) in Hereditary Transthyretin-Mediated Amyloid Polyneuropathy

Author

Coelho, Teresa, Ando, Yukio, Benson, Merrill D, Berk, John L, Waddington-Cruz, Márcia, Dyck, Peter J, Gillmore, Julian D, Khella, Sami L, Litchy, William J, Obici, Laura, Monteiro, Cecilia, Tai, Li-Jung, Viney, Nicholas J, Buchele, Gustavo, Brambatti, Michela, Jung, Shiangtung W, St. L. O’Dea, Louis, Tsimikas, Sotirios, Schneider, Eugene, Geary, Richard S, Monia, Brett P, and Gertz, Morie

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Rare Diseases, Clinical Trials and Supportive Activities, Neurosciences, Orphan Drug, Clinical Research, Peripheral Neuropathy, Neurodegenerative, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, AKCEA-TTR-L-rx, Antisense oligonucleotide, Clinical trial design, Hereditary transthyretin-mediated amyloid polyneuropathy, Phase 3 clinical trial, AKCEA-TTR-Lrx, Clinical sciences
Abstract

IntroductionAKCEA-TTR-LRx is a ligand-conjugated antisense (LICA) drug in development for the treatment of hereditary transthyretin amyloidosis (hATTR), a fatal disease caused by mutations in the transthyretin (TTR) gene. AKCEA-TTR-LRx shares the same nucleotide sequence as inotersen, an antisense medicine approved for use in hATTR polyneuropathy (hATTR-PN). Unlike inotersen, AKCEA-TTR-LRx is conjugated to a triantennary N-acetylgalactosamine moiety that supports receptor-mediated uptake by hepatocytes, the primary source of circulating TTR. This advanced design increases drug potency to allow for lower and less frequent dosing. The NEURO-TTRansform study will investigate whether AKCEA-TTR-LRx is safe and efficacious, with the aim of improving neurologic function and quality of life in hATTR-PN patients.Methods/designApproximately 140 adults with stage 1 (independent ambulation) or 2 (requires ambulatory support) hATTR-PN are anticipated to enroll in this multicenter, open-label, randomized, phase 3 study. Patients will be assigned 6:1 to AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks or inotersen 300 mg once weekly until the prespecified week 35 interim efficacy analysis, after which patients receiving inotersen will receive AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks. All patients will then receive AKCEA-TTR-LRx through the remainder of the study treatment period. The final efficacy analysis at week 66 will compare the AKCEA-TTR-LRx arm with the historical placebo arm from the phase 3 trial of inotersen (NEURO-TTR). The primary outcome measures are between-group differences in the change from baseline in serum TTR, modified Neuropathy Impairment Score + 7, and Norfolk Quality of Life-Diabetic Neuropathy questionnaire.ConclusionNEURO-TTRansform is designed to determine whether targeted delivery of AKCEA-TTR-LRx to hepatocytes with lower and less frequent doses will translate into clinical and quality-of-life benefits for patients with hATTR-PN.Trial registrationThe study is registered at ClinicalTrials.gov (NCT04136184) and EudraCT (2019-001698-10).

Published
2021

6. Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen

Author

Coelho, Teresa, Waddington Cruz, Márcia, Chao, Chi-Chao, Parman, Yeşim, Wixner, Jonas, Weiler, Markus, Barroso, Fabio A., Dasgupta, Noel R., Jung, Shiangtung W., Schneider, Eugene, Viney, Nicholas J., Dyck, P. James B., Ando, Yukio, Gillmore, Julian D., Khella, Sami, Gertz, Morie A., Obici, Laura, and Berk, John L.

Published
2023
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7. Long-term efficacy and safety of inotersen for hereditary transthyretin amyloidosis: NEURO-TTR open-label extension 3-year update

Author

Brannagan, Thomas H., Coelho, Teresa, Wang, Annabel K., Polydefkis, Michael J., Dyck, Peter J., Berk, John L., Drachman, Brian, Gorevic, Peter, Whelan, Carol, Conceição, Isabel, Plante-Bordeneuve, Violaine, Merlini, Giampaolo, Obici, Laura, Plana, Josep Maria Campistol, Gamez, Josep, Kristen, Arnt V., Mazzeo, Anna, Gentile, Luca, Narayana, Arvind, Olugemo, Kemi, Aquino, Peter, Benson, Merrill D., and Gertz, Morie

Published
2022
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9. Impact de la sévérité de la polyneuropathie à baseline sur la réponse au traitement par le vutrisiran dans l’étude de phase 3 HELIOS-A

Author

Luigetti, Marco, primary, Quan, Dianna, additional, Berk, John L., additional, Conceição, Isabel, additional, Misumi, Yohei, additional, Chao, Chi-Chao, additional, Bender, Shaun, additional, Aldinc, Emre, additional, Vest, John, additional, Lainé, Anne-Félice, additional, and Adams, David, additional

Published
2024
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10. Assessing mNIS+7Ionis and international neurologists' proficiency in a familial amyloidotic polyneuropathy trial

Author

Dyck, Peter J, Kincaid, John C, Dyck, P James B, Chaudhry, Vinay, Goyal, Namita A, Alves, Christina, Salhi, Hayet, Wiesman, Janice F, Labeyrie, Celine, Robinson‐Papp, Jessica, Cardoso, Márcio, Laura, Matilde, Ruzhansky, Katherine, Cortese, Andrea, Brannagan, Thomas H, Khoury, Julie, Khella, Sami, Waddington‐Cruz, Márcia, Ferreira, João, Wang, Annabel K, Pinto, Marcus V, Ayache, Samar S, Benson, Merrill D, Berk, John L, Coelho, Teresa, Polydefkis, Michael, Gorevic, Peter, Adams, David H, Plante‐Bordeneuve, Violaine, Whelan, Carol, Merlini, Giampaolo, Heitner, Stephen, Drachman, Brian M, Conceição, Isabel, Klein, Christopher J, Gertz, Morie A, Ackermann, Elizabeth J, Hughes, Steven G, Mauermann, Michelle L, Bergemann, Rito, Lodermeier, Karen A, Davies, Jenny L, Carter, Rickey E, and Litchy, William J

Subjects
Neurodegenerative, Peripheral Neuropathy, Neurosciences, Chronic Pain, Clinical Research, Pain Research, Adult, Aged, Aged, 80 and over, Amyloid Neuropathies, Familial, Cohort Studies, Diagnostic Techniques, Neurological, Disability Evaluation, Female, Humans, International Cooperation, Male, Middle Aged, Neural Conduction, Neurologists, Oligonucleotides, Outcome Assessment, Health Care, Severity of Illness Index, disability, familial amyloidotic polyneuropathy, neurophysiologic tests, oligonucleotide trials, peripheral neuropathy, polyneuropathy signs, proficiency, Medical and Health Sciences, Neurology & Neurosurgery
Abstract

IntroductionPolyneuropathy signs (Neuropathy Impairment Score, NIS), neurophysiologic tests (m+7Ionis ), disability, and health scores were assessed in baseline evaluations of 100 patients entered into an oligonucleotide familial amyloidotic polyneuropathy (FAP) trial.MethodsWe assessed: (1) Proficiency of grading neurologic signs and correlation with neurophysiologic tests, and (2) clinometric performance of modified NIS+7 neurophysiologic tests (mNIS+7Ionis ) and its subscores and correlation with disability and health scores.ResultsThe mNIS+7Ionis sensitively detected, characterized, and broadly scaled diverse polyneuropathy impairments. Polyneuropathy signs (NIS and subscores) correlated with neurophysiology tests, disability, and health scores. Smart Somatotopic Quantitative Sensation Testing of heat as pain 5 provided a needed measure of small fiber involvement not adequately assessed by other tests.ConclusionsSpecially trained neurologists accurately assessed neuropathy signs as compared to referenced neurophysiologic tests. The score, mNIS+7Ionis , broadly detected, characterized, and scaled polyneuropathy abnormality in FAP, which correlated with disability and health scores. Muscle Nerve 56: 901-911, 2017.

Published
2017

12. Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

Author

Vita, Giuseppe, Rizzo, Vincenzo, Russo, Massimo, Mazzeo, Anna, Gentile, Luca, Berk, John L, Brueckner, Caitlin, Lazzari, Victoria, Wiesman, Janice, DeLong, Douglas, Victory, Jennifer, Dalton, James, May, John, Gilmore, Catherine, Attarian, Shahram, Diallo, Saran, Delmont, Emilien, Pouget, Jean, Verschueren, Annie, Grapperon, Aude-Marie, Campana-Salort, Emmanuelle, Conceição, Isabel M, Lopes, Ana, Lamas, Filipa, Neves, Carlos, Castro, Jose, Pereira, Pedro, Castro, Isabel, Franco, Ana, Santos, Miguel Oliveira, de Azevedo Coutinho, Conceição, Falcao de Campos, Catarina, Coelho, Teresa, Hipólito Reis, Antonio, Correia, Nuno, Perez, Javier M, Martins da Silva, Ana, Alves, Cristina, Cardoso, Marcio, Valdrez, Katia, Monte, Julia R, Pessoa, Bernardete, Guimaraes, Nadia, Freitas, Monica, Ramalho, Joana, Ferreira, Natalia, Kuzume, Daisuke, Tard, Celine, Waucquier, Nawal, Rougeaux, Isabelle, Brice, Sylvie, Kasprzyk, Emmanuelle, Elrezzi, Elise, Meguig, Sayah, Hachulla, Eric, Gauvain, Clement, Migaud-Chervy, Maria-Claire, Deplanque, Dominique, Jozefowicz, Elsa, Lebellec, Loic, Adams, David, Balaya-Gouraya, Line, Jehan Lacour, Nathalie, Bournane, Halima, Martin, Nathalie, Elabed, Mongia, Sacko, Niamey, Boubrit, Yasmine, Gaouar, Amina, Rakotondratafika, Fetra, Théaudin-Saliou, Marie, Cauquil-Michon, Cécile, Labeyrie, Celine, Not, Adeline, Al-Salameh, Abdallah, Lecoq, Anne-Lise, Stephant, Maeva, Echaniz-Laguna, Andoni, Becquemont, Laurent, Beaudonnet, Guillemette, Algalarrondo, Vincent, Eliahou, Ludivine, Slama, Michel S, Rousseau, Antoine, Signate, Aissatou, Berthelot, Emeline, Inamo, Jocelyn, Planté-Bordeneuve, Violaine, Vervoitte, Laetitia, Focseneanu, Cecile, Gendre, Thierry, Arrouasse, Raphaele, Ayache, Samar S., Ernande, Laura, Le Corvoisier, Philippe, Salhi, Hayet, Choumert, Ariane, Ehinger, Vincent, Ruiz, Julie, Charlin, Cyril, Megelin, Thomas, Brannagan III, Thomas H, Fayerman, Raisy, Kim, Arreum, Paras, Allan, Gonzalez, Leidy J, Tsang, Steven, Wajnsztajn, Fernanda, Shije, Jeffrey, Ulane, Christina, Kleyman, Inna, Weimer, Louis, Cioroiu, Comana, Lambrianides, Sakis, Abu-Manneh, Rana, Zamba-Papanicolaou, Eleni, Agathangelou, Petros, Leonidou, Eleni, Tada, Satoshi, Fujita, Akemi, Nagai, Masahiro, Ando, Rina, Hosokawa, Yuko, Yamanishi, Yuki, Overcash, J. Scott, Giardino, Elena, Boyer, Leslie, Dang, Lien, Le, An, Nguyen, Tyler, Giang, Lien, Sellers, Peter, Tran, Leyla, Truong, Nghi, Vinas, Maita, Hrkman, Nicole, Miller, Sarah, Nguyen, David, Smith, Ashley, Pu, Helen, Li, Steve, Vuong, Thao, Dioso, Holly, Green, Sinikka, Lee, Kia, Chu, Hanh, Waters, Michael, Coskun, Derya J, Zepeda, Karla A, O'Riordan, William, Obici, Laura, Cortese, Andrea, Lozza, Alessandro, Merlini, Giampaolo, Rosti, Vittorio, Sabatelli, Mario, Bisogni, Giulia, Bernardo, Daniela, Luigetti, Marco, Di Paolantonio, Andrea, Guglielmino, Valeria, Romano, Angela, Nienhuis, Hans, Bulthuis-Kuiper, Janita, Kristen, Arnt V, Gerk, Olga, Ulbricht, Hannah, Taylor, Lenka, Meyle, Eva, Kleinschmidt, Natalia, Meyrath, David, Noe-Schwenn, Simone, Meng, Ulrike, Bauer, Ralf, aus dem Siepen, Fabian, Hein, Selina, Takahashi, Tetsuya, Oshita, Tomohiko, Koujin, Yoko, Neshige, Shuichiro, Nezu, Tomohisa, Segawa, Akiko, Ueno, Hiroki, Morino, Hiroyuki, Campistol, Josep M, Rodas Marin, Lida Maria, Blasco Pelicano, Josep Miquel, Dávila, Lucía Galán, Palacios, Marta, Pytel Cordoba, Vanesa, Guerrero Sola, Antonio, Horga, Alejandro, García Feijoo, Julián, Perez de Isla, Leopoldo, Marques Júnior, Wilson, Moscardini, Mariana, Litcanov, Debora Cristina, Viera Lima, Ana Flavia, Rodrigues, Leonardo, Marques Coutinho, Barbara, Moreira, Carolina Lavigne, Daccach Marques, Vanessa, Munoz Beamud, Francisco, Gragera Martínez, Álvaro, Borrachero, Cristina, Losada López, Inés Asunción, Cisneros Barroso, Eugenia, Rodríguez Rodríguez, Adrián, Sanz, Monica, Rigo Oliver, Elena, González Moreno, Juan, Gamez Martinez, Jose M, Descals, Cristina, Uson, Mercedes, Jose Vega, Francisco, Figuerola, Antoni, Montala, Carles, Waddington-Cruz, Márcia, Dias da Silva, Moises, Gervais de Santa Rosa, Renata, Pinto, Luiz Felipe, Pinto, Marcus Vinicius, Cardoso Berensztejn, Amanda, Barroso, Fabio, Lautre, Andrea, Orellana, Lucas G, González-Duarte Briseño, Maria Alejandra, Cárdenas-Soto, Karla, Jiménez López, Brenda Poled, Pérez-Castañeda, Sandra Lorena, Cantú Brito, Carlos Gerardo, Rivera de la Parra, David, Hernandez Reyes, Jose Pablo, del Mar Saniger Alba, Maria, Criollo Mora, Elia, Parman, Yesim, Rezzan, Kus Jülide, Sahin, Erdi, Serbest, Nail G, Durmus, Hacer, Cakar, Arman, Tugal Tutkun, Nuriye Ilknur, Karamursel, Sacit, Elitok, Ali, Sirin Inan, Nermin G, Altinkurt, Emre, Polydefkis, Michael, Ye, Jing, Allen, Adriane C, Chaudhry, Vinay, Jarrett, Raquel, Bressler, Neil, Burks, Kathleen L, Liu, Qingfeng, Khoshnoodi, Mohammad, Judge, Daniel P, Vista, Geno, Shah, Syed Mahmood, Hamaguchi, Hirotoshi, Oda, Junko, Fukase, Emi, Taniguchi, Ikuko, Oda, Tetsuya, Endo, Hironobu, Shimomura, Masahiro, Katanazaka, Kimitaka, Koto, Shusuke, Nakano, Takahiro, Scheid, Christof, Zueiter, Andreas, Pester, Lars, Walter, Doreen, Özdemir, Betül, Frenzel, Lukas F, Holtick, Udo, Oh, Jeeyoung, Kim, Hee Jin, Shin, Hyun Jin, Choi, Kyomin, Yamashita, Taro, Ueda, Mitsuharu, Masuda, Teruaki, Misumi, Yohei, Ueda, Akihiko, Nakahara, Keiichi, Yorita, Akiko, Tsuruhisa, Seiko, Taniwaki, Takayuki, Harada, Masaya, Moritaka, Taiga, Sakurada, Naonori, Mauricio, Elizabeth A, Baskin, Amber, Dimberg, Elliot, Dispenzieri, Angela, Fonder, Amie, Hobbs, Miriam, Russell, Stephen J, Dyck, Peter, Gonsalves, Wilson, Leung, Nelson, Witzig, Thomas E, Zeldenrust, Steven R, Hwa, Lisa, Kapoor, Prashant, Kumar, Shaji K, Lin, Yi, Lust, John A, Rajkumar, Vincent S, Dingli, David, Gertz, Morie A, Go, Ronald, Hayman, Suzanne R, Dalia, Samir, Carrillo, Esmeralda, Gorevic, Peter, Mason, Garnette, Chao, Chi-Chao, Lee, Ming-Jen, Su, Jen-Jen, Hsieh, Sung-Tsang, Tsai, Li-Kai, Yeh, Shin-Joe, Yang, Chih-Chao, Ajroud-Driss, Senda Ajroud-Driss, Casey, Patricia, Joslin, Benjamin C, Freimer, Miriam, Sankey, Alison, Kenepp, Amanda, Heintzman, Sarah, LoRusso, Samantha, Hokezu, Youichi, Kim, Byoung-Joon, Kim, JuHyeon, Lee, Ga Yeon, Cho, Eun Bin, Jeon, Eun-Seok, Min, Ju-Hong, Seok, Jin Myoung, Lee, Hye Lim, Park, Jae Hong, Sekijima, Yoshiki, Miyazawa, Chinatsu, Kato, Nagaaki, Kishida, Dai, Hineno, Akiyo, Kodaira, Minori, Yoshinaga, Tsuneaki, Miyahara, Teruyoshi, Imai, Akira, Matsumoto, Kazuhiko, Lin, Kon-Ping, Lee, Yi-Chung, Wixner, Jonas, Falk, Malin, Pilebro, Bjorn, Suhr, Ole, Lindqvist, Per, Soderberg, Karin, Pedrosa-Domellöf, Fatima, Anan, Intissar, Nordh, Erik, Tournev, Ivaylo, Zhelyazkova-Glaveeva, Sashka, Cherneva, Zheyna, Sarafov, Staiko, Chamova, Teodora, Cherninkova-Gopina, Sylvia, Schmidt, Hartmut H, Friebel, Frauke, Zibert, Andree, Mihailovic, Natasa, Schubert, Friederike, Vorona, Elena, Lahme, Larissa, Huesing-Kabar, Anna, Schilling, Matthias, Kabar, Iyad, Gillmore, Julian D, Martinez-Naharro, Ana, Chacko, Liza, Cohen, Oliver, Law, Steven, Rezk, Tamer, Lachmann, Helen J, Quan, Dianna, Blume, Brianna, Dixon, Stacy, Low, Soon Chai, Chan, Soo Looi, Lim, He Eng Li, Goh, Khean Jin, Mezei, Michelle M, Kraus, Deborah, Jack, Kristin, Wade, N. Kevin, Lopate, Glenn, Zwijack, Brittany, Florence, Julaine, Sommerville, R. Brian, Stewart, Graeme, Ryder, Julie, Mekhael, Linda, Taylor, Mark, Suan, Daniel, Wells, Karen, Stone, Paula, Itoya, Amenze, Owusu-Sekyere, Mercy, Thai, Desmond, Chahine, Ilonah, Pedrosa, Salve, Do, Thi Hoa (Therese), González-Duarte, Alejandra, Kyriakides, Theodoros, Ajroud-Driss, Senda, Mauricio, Elizabeth, Brannagan, Thomas H, III, Aldinc, Emre, Wang, Jing Jing, White, Matthew T, Vest, John, Berber, Erhan, and Sweetser, Marianne T

Published
2021
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14. Impact of vutrisiran on exploratory cardiac parameters in hereditary transthyretin‐mediated amyloidosis with polyneuropathy

Author

Garcia‐Pavia, Pablo, primary, Grogan, Martha, additional, Kale, Parag, additional, Berk, John L., additional, Maurer, Mathew S., additional, Conceição, Isabel, additional, Di Carli, Marcelo, additional, Solomon, Scott D., additional, Chen, Chongshu, additional, Yureneva, Elena, additional, Vest, John, additional, and Gillmore, Julian D., additional

Published
2024
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15. Primary Results From APOLLO-B Open-label Extension Study Of Patisiran In Patients With Transthyretin Cardiac Amyloidosis

Author

Maurer, Mathew S., primary, Berk, John L., additional, Hanna, Mazen A., additional, Gillmore, Julian D., additional, Schwartzmann, Pedro V., additional, Lairez, Olivier, additional, Hatano, Masaru, additional, Cho, Hyun-Jai, additional, van der Meer, Peter, additional, White, Matthew T., additional, Yureneva, Elena, additional, Sweetser, Marianne T., additional, Jay, Patrick Y., additional, Vest, John, additional, and Fontana, Marianna, additional

Published
2024
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16. Effect of Eplontersen on Cardiac Structure and Function in Patients With Hereditary Transthyretin Amyloidosis

Author

Masri, Ahmad, primary, Maurer, Mathew S., additional, Claggett, Brian L., additional, Kulac, Ian, additional, Waddington Cruz, Marcia, additional, Conceição, Isabel, additional, Weiler, Markus, additional, Berk, John L., additional, Gertz, Morie, additional, Gillmore, Julian D., additional, Rush, Stephen, additional, Chen, Jersey, additional, Zhou, Wunan, additional, Kwoh, Jesse, additional, Duran, Jason M., additional, Tsimikas, Sotirios, additional, and Solomon, Scott D., additional

Published
2023
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17. ATTR amyloidosis during the COVID-19 pandemic: insights from a global medical roundtable

Author

Brannagan, III, Thomas H., Auer-Grumbach, Michaela, Berk, John L., Briani, Chiara, Bril, Vera, Coelho, Teresa, Damy, Thibaud, Dispenzieri, Angela, Drachman, Brian M., Fine, Nowell, Gaggin, Hanna K., Gertz, Morie, Gillmore, Julian D., Gonzalez, Esther, Hanna, Mazen, Hurwitz, David R., Khella, Sami L., Maurer, Mathew S., Nativi-Nicolau, Jose, Olugemo, Kemi, Quintana, Luis F., Rosen, Andrew M., Schmidt, Hartmut H., Shehata, Jacqueline, Waddington-Cruz, Marcia, Whelan, Carol, and Ruberg, Frederick L.

Published
2021
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18. Inotersen preserves or improves quality of life in hereditary transthyretin amyloidosis

Author

Coelho, Teresa, Yarlas, Aaron, Waddington-Cruz, Marcia, White, Michelle K., Sikora Kessler, Asia, Lovley, Andrew, Pollock, Michael, Guthrie, Spencer, Ackermann, Elizabeth J., Hughes, Steven G., Karam, Chafic, Khella, Sami, Gertz, Morie, Merlini, Giampaolo, Obici, Laura, Schmidt, Hartmut H., Polydefkis, Michael, Dyck, P. James B., Brannagan III, Thomas H., Conceição, Isabel, Benson, Merrill D., and Berk, John L.

Published
2020
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19. Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Author

González-Duarte, Alejandra, Berk, John L., Quan, Dianna, Mauermann, Michelle L., Schmidt, Hartmut H., Polydefkis, Michael, Waddington-Cruz, Márcia, Ueda, Mitsuharu, Conceição, Isabel M., Kristen, Arnt V., Coelho, Teresa, Cauquil, Cécile A., Tard, Céline, Merkel, Madeline, Aldinc, Emre, Chen, Jihong, Sweetser, Marianne T., Wang, Jing Jing, and Adams, David

Published
2020
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20. Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis

Author

Maurer, Mathew S., primary, Kale, Parag, additional, Fontana, Marianna, additional, Berk, John L., additional, Grogan, Martha, additional, Gustafsson, Finn, additional, Hung, Rebecca R., additional, Gottlieb, Robert L., additional, Damy, Thibaud, additional, González-Duarte, Alejandra, additional, Sarswat, Nitasha, additional, Sekijima, Yoshiki, additional, Tahara, Nobuhiro, additional, Taylor, Mark S., additional, Kubanek, Milos, additional, Donal, Erwan, additional, Palecek, Tomas, additional, Tsujita, Kenichi, additional, Tang, W.H. Wilson, additional, Yu, Wen-Chung, additional, Obici, Laura, additional, Simões, Marcus, additional, Fernandes, Fábio, additional, Poulsen, Steen Hvitfeldt, additional, Diemberger, Igor, additional, Perfetto, Federico, additional, Solomon, Scott D., additional, Di Carli, Marcelo, additional, Badri, Prajakta, additional, White, Matthew T., additional, Chen, Jihong, additional, Yureneva, Elena, additional, Sweetser, Marianne T., additional, Jay, Patrick Y., additional, Garg, Pushkal P., additional, Vest, John, additional, and Gillmore, Julian D., additional

Published
2023
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25. Correction to: Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Author

González-Duarte, Alejandra, Berk, John L., Quan, Dianna, Mauermann, Michelle L., Schmidt, Hartmut H., Polydefkis, Michael, Waddington-Cruz, Márcia, Ueda, Mitsuharu, Conceição, Isabel M., Kristen, Arnt V., Coelho, Teresa, Cauquil, Cécile A., Tard, Céline, Merkel, Madeline, Aldinc, Emre, Chen, Jihong, Sweetser, Marianne T., Wang, Jing Jing, and Adams, David

Published
2020
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26. Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis: Analysis of the APOLLO Study

Author

Solomon, Scott D., Adams, David, Kristen, Arnt, Grogan, Martha, González-Duarte, Alejandra, Maurer, Mathew S., Merlini, Giampaolo, Damy, Thibaud, Slama, Michel S., Brannagan, Thomas H., III, Dispenzieri, Angela, Berk, John L., Shah, Amil M., Garg, Pushkal, Vaishnaw, Akshay, Karsten, Verena, Chen, Jihong, Gollob, Jared, Vest, John, and Suhr, Ole

Published
2019
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27. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy.

Author

Coelho, Teresa, Marques Jr, Wilson, Dasgupta, Noel R., Chao, Chi-Chao, Parman, Yeşim, França Jr, Marcondes Cavalcante, Guo, Yuh-Cherng, Wixner, Jonas, Ro, Long-Sun, Calandra, Cristian R., Kowacs, Pedro A., Berk, John L., Obici, Laura, Barroso, Fabio A., Weiler, Markus, Conceição, Isabel, Jung, Shiangtung W., Buchele, Gustavo, Brambatti, Michela, and Chen, Jersey

Subjects
TRANSTHYRETIN, POLYNEUROPATHIES, CLINICAL trials, AMYLOIDOSIS, CARDIAC amyloidosis, ARRHYTHMIA, CEREBRAL hemorrhage
Abstract

Key Points: Question: Is the antisense oligonucleotide eplontersen associated with changes in serum transthyretin concentration and improvement in neuropathy symptoms among adults with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy? Findings: In this open-label study that enrolled 168 patients (144 assigned to subcutaneous eplontersen) and included 60 historical placebo patients, the eplontersen treatment group demonstrated changes from baseline to week 65/66 consistent with significantly lower serum transthyretin concentration (−81.7% vs −11.2%), less neuropathy impairment, and better quality of life compared with the historical placebo group. Meaning: Among adults with ATTRv polyneuropathy, the eplontersen treatment group had lower serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013–November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group. Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, –22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire–Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, –4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was −81.7% with eplontersen and −11.2% with placebo (difference, −70.4% [95% CI, −75.2% to −65.7%]; P <.001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, −24.8 [95% CI, −31.0 to −18.6; P <.001) and for Norfolk QoL-DN (−5.5 vs 14.2; difference, −19.7 [95% CI, −25.6 to −13.8]; P <.001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10 This open-label, single-group, phase 3 trial evaluates eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in adults with hereditary amyloid transthyretin (ATTRv) polyneuropathy at 40 sites in 15 countries, compared with historical controls. [ABSTRACT FROM AUTHOR]

Published
2023
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28. Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen

Author

Coelho, Teresa, primary, Waddington Cruz, Márcia, additional, Chao, Chi-Chao, additional, Parman, Yeşim, additional, Wixner, Jonas, additional, Weiler, Markus, additional, Barroso, Fabio A., additional, Dasgupta, Noel R., additional, Jung, Shiangtung W., additional, Schneider, Eugene, additional, Viney, Nicholas J., additional, Dyck, P. James B., additional, Ando, Yukio, additional, Gillmore, Julian D., additional, Khella, Sami, additional, Gertz, Morie A., additional, Obici, Laura, additional, and Berk, John L., additional

Published
2022
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29. 77 HELIOS-A: 18-MONTH EXPLORATORY CARDIAC RESULTS FROM THE PHASE 3 STUDY OF VUTRISIRAN IN PATIENTS WITH HEREDITARY TRANSTHYRETIN-MEDIATED AMYLOIDOSIS

Author

Mussinelli(on Behalf Of The Authors), Roberta, primary, Garcia-pavia, Pablo, additional, Gillmore, Julian D, additional, Kale, Parag, additional, Berk, John L, additional, Maurer, Mathew S, additional, Conceição, Isabel, additional, Dicarli, Marcelo, additional, Solomon, Scott, additional, Chen, Chongshu, additional, Arum, Seth, additional, Vest, John, additional, and Grogan, Martha, additional

Published
2022
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30. 137 PRIMARY RESULTS FROM APOLLO-B, A PHASE 3 STUDY OF PATISIRAN IN PATIENTS WITH TRANSTHYRETIN-MEDIATED AMYLOIDOSIS WITH CARDIOMYOPATHY

Author

Longhi(on Behalf Of), Simone, primary, Maurer, Mathew S, additional, Fontana, Marianna, additional, Berk, John L, additional, Gustafsson, Finn, additional, Simões, Marcos, additional, Grogan, Martha, additional, Fernandes, Fábio, additional, Gottlieb, Robert L, additional, Kubanek, Milos, additional, Poulsen, Steen, additional, Damy, Thibaud, additional, Diemberger, Igor, additional, Tahara, Nobuhiro, additional, Yu, Wen-chuhg, additional, Wilson Tang, W H, additional, Obici, Laura, additional, González-duarte, Alejandra, additional, Sekijima, Yoshiki, additional, White, Matthew T, additional, Yureneva, Elena, additional, Jay, Patrick Y, additional, Vest, John, additional, and Gillmore, Julian D, additional

Published
2022
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32. Liver‐directed drugs for transthyretin‐mediated amyloidosis

Author

Brannagan, Thomas H., primary, Berk, John L., additional, Gillmore, Julian D., additional, Maurer, Mathew S., additional, Waddington‐Cruz, Márcia, additional, Fontana, Marianna, additional, Masri, Ahmad, additional, Obici, Laura, additional, Brambatti, Michela, additional, Baker, Brenda F., additional, Hannan, Lisa A., additional, Buchele, Gustavo, additional, Viney, Nick J., additional, Coelho, Teresa, additional, and Nativi‐Nicolau, Jose, additional

Published
2022
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33. An additive destabilising effect of compound T60I and V122I substitutions in ATTRv amyloidosis

Author

Prokaeva, Tatiana, primary, Klimtchuk, Elena S., additional, Feschenko, Polina, additional, Spencer, Brian, additional, Cui, Haili, additional, Burks, Eric J., additional, Aslebagh, Roshanak, additional, Muneeruddin, Khaja, additional, Shaffer, Scott A., additional, Varghese, Elizabeth, additional, Berk, John L., additional, and Connors, Lawreen H., additional

Published
2022
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34. Light Chain Testing Abnormalities Among Patients With Transthyretin Amyloid Cardiomyopathy Referred for Technetium-99m Pyrophosphate Imaging

Author

Alreshq, Rabah, primary, Cozzolino, Matthew, additional, Lilleness, Brian, additional, Pipilas, Alexandra, additional, Mendelson, Lisa, additional, Joshi, Tracy, additional, Muralidhar, Varsha, additional, Guardino, Eric, additional, Berk, John L., additional, Siddiqi, Omar K., additional, Gopal, Deepa M., additional, Sanchorawala, Vaishali, additional, and Ruberg, Frederick L., additional

Published
2022
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37. Characterising diflunisal as a transthyretin kinetic stabilizer at relevant concentrations in human plasma using subunit exchange.

Author

Tsai, Felix J., Nelson, Luke T., Kline, Gabriel M., Jäger, Marcus, Berk, John L., Sekijima, Yoshiki, Powers, Evan T., and Kelly, Jeffery W.

Subjects
TRANSTHYRETIN, SMALL molecules, PHASE separation, POLYNEUROPATHIES, NONSTEROIDAL anti-inflammatory agents
Abstract

Transthyretin (TTR) dissociation is the rate limiting step for both aggregation and subunit exchange. Kinetic stabilisers, small molecules that bind to the native tetrameric structure of TTR, slow TTR dissociation and inhibit aggregation. One such stabiliser is the non-steroidal anti-inflammatory drug (NSAID), diflunisal, which has been repurposed to treat TTR polyneuropathy. Previously, we compared the efficacy of diflunisal, tafamidis, tolcapone, and AG10 as kinetic stabilisers for transthyretin. However, we could not meaningfully compare diflunisal because we were unsure of its plasma concentration after long-term oral dosing. Herein, we report the diflunisal plasma concentrations measured by extraction, reversed phase HPLC separation, and fluorescence detection after long-term 250 mg BID oral dosing in two groups: a placebo-controlled diflunisal clinical trial group and an open-label Japanese polyneuropathy treatment cohort. The measured mean diflunisal plasma concentration from both groups was 282.2 μ M ± 143.7 μ M (mean ± standard deviation). Thus, quantification of TTR kinetic stabilisation using subunit exchange was carried out at 100, 200, 300, and 400 μM diflunisal concentrations, all observed in patients after 250 mg BID oral dosing. A 250 μ M diflunisal plasma concentration reduced the wild-type TTR dissociation rate in plasma by 95%, which is sufficient to stop transthyretin aggregation, consistent with the clinical efficacy of diflunisal for ameliorating transthyretin polyneuropathy. [ABSTRACT FROM AUTHOR]

Published
2023
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38. An additive destabilising effect of compound T60I and V122I substitutions in ATTRv amyloidosis.

Author

Prokaeva, Tatiana, Klimtchuk, Elena S., Feschenko, Polina, Spencer, Brian, Cui, Haili, Burks, Eric J., Aslebagh, Roshanak, Muneeruddin, Khaja, Shaffer, Scott A., Varghese, Elizabeth, Berk, John L., and Connors, Lawreen H.

Subjects
AMYLOIDOSIS, CONGESTIVE heart failure, ISOELECTRIC focusing, AMYLOID plaque, ATRIAL fibrillation, CARDIAC amyloidosis, AMYLOID
Abstract

The amyloidogenic transthyretin (TTR) variant, V122I, occurs in 4% of the African American population and frequently presents as a restricted cardiomyopathy. While heterozygosity for TTR V122I predominates, several compound heterozygous cases have been previously described. Herein, we detail features of ATTRv amyloidosis associated with novel compound heterozygous TTR mutation, T60I/V122I and provide evidence supporting the amyloidogenecity of T60I. A 63-year-old African American female presented with atrial fibrillation, congestive heart failure, autonomic and peripheral neuropathy. In vitro studies of TTR T60I and V122I were undertaken to compare the biophysical properties of the proteins. Congophilic deposits in a rectal biopsy were immunohistochemically positive for TTR. Serum screening by isoelectric focussing revealed two TTR variants in the absence of wild-type protein. DNA sequencing identified compound heterozygous TTR gene mutations, c.239C > T and c.424G > A. Adipose amyloid deposits were composed of both T60I and V122I. While kinetic stabilities of T60I and V122I variants were similar, distinct thermodynamic stabilities and amyloid growth kinetics were observed. This report provides clinical and experimental results supporting the amyloidogenic nature of a novel TTR T60I variant. In vitro data indicate that the destabilising effect of individual T60I and V122I variants appears to be additive rather than synergistic. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Predictors of hematologic response and survival with stem cell transplantation in AL amyloidosis: A 25‐year longitudinal study

Author

Gustine, Joshua N., primary, Staron, Andrew, additional, Szalat, Raphael E., additional, Mendelson, Lisa M., additional, Joshi, Tracy, additional, Ruberg, Frederick L., additional, Siddiqi, Omar, additional, Gopal, Deepa M., additional, Edwards, Camille V., additional, Havasi, Andrea, additional, Kaku, Michelle, additional, Lau, K. H. Vincent, additional, Berk, John L., additional, Sloan, J. Mark, additional, and Sanchorawala, Vaishali, additional

Published
2022
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40. Guidelines and new directions in the therapy and monitoring of ATTRv amyloidosis

Author

Ando, Yukio, primary, Adams, David, additional, Benson, Merrill D., additional, Berk, John L., additional, Planté-Bordeneuve, Violaine, additional, Coelho, Teresa, additional, Conceição, Isabel, additional, Ericzon, Bo-Göran, additional, Obici, Laura, additional, Rapezzi, Claudio, additional, Sekijima, Yoshiki, additional, Ueda, Mitsuharu, additional, Palladini, Giovanni, additional, and Merlini, Giampaolo, additional

Published
2022
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41. Tissue biopsy for the diagnosis of amyloidosis : experience from some centres

Author

Benson, Merrill D., Berk, John L., Dispenzieri, Angela, Damy, Thibaud, Gillmore, Julian D., Hazenberg, Bouke P., Lavatelli, Francesca, Picken, Maria M., Röcken, Christoph, Schönland, Stefan, Ueda, Mitsuharu, Westermark, Per, Benson, Merrill D., Berk, John L., Dispenzieri, Angela, Damy, Thibaud, Gillmore, Julian D., Hazenberg, Bouke P., Lavatelli, Francesca, Picken, Maria M., Röcken, Christoph, Schönland, Stefan, Ueda, Mitsuharu, and Westermark, Per

Abstract

A reliable diagnosis of amyloidosis is usually based on a tissue biopsy. With increasing options for specific treatments of the different amyloid diseases, an exact and valid diagnosis including determination of the biochemical fibril nature is imperative. Biopsy sites as well as amyloid typing principles vary and this paper describes methods employed at some laboratories specialised in amyloidosis in Europe, Japan and USA.

Published
2022
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44. Impact of baseline polyneuropathy severity on patisiran treatment outcomes in the APOLLO trial.

Author

Quan, Dianna, Obici, Laura, Berk, John L., Ando, Yukio, Aldinc, Emre, White, Matthew T., and Adams, David

Subjects
TREATMENT effectiveness, GRIP strength, WALKING speed, BIOMARKERS, AMYLOIDOSIS, POLYNEUROPATHIES
Abstract

Assess how baseline polyneuropathy severity impacts response to patisiran regarding neurologic impairment and quality of life (QOL) in patients with hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis). This post hoc analysis grouped patients from the Phase 3 APOLLO study (n = 225) by baseline Neuropathy Impairment Score (NIS) into quartiles: 6–<31; 31–<57; 57–<85.5; 85.5–141.6. Neurologic impairment (modified NIS+7 [mNIS+7], NIS total score), disability (Rasch-built Overall Disability Scale [R-ODS]), gait speed (10-meter walk test [10-MWT]), grip strength, and QOL (Norfolk Quality of Life-Diabetic Neuropathy [Norfolk QOL-DN] questionnaire) were assessed. Across all baseline NIS quartiles, patisiran improved several clinical markers of disease compared with placebo at 18 months. Patients in lower NIS quartiles, treated with patisiran earlier in the disease course, maintained better scores in mNIS+7, NIS total score, R-ODS, 10-MWT, grip strength, and Norfolk QOL-DN versus those in higher NIS quartiles, while placebo-treated patients experienced worsening of all functional measures after 18 months across all quartiles. Patisiran treatment improved neurologic function and QOL across a wide range of baseline polyneuropathy severities versus placebo. Timing of treatment initiation in patients with ATTRv amyloidosis remains critical for the preservation of function. (ClinicalTrials.gov number, NCT01960348) [ABSTRACT FROM AUTHOR]

Published
2023
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45. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial.

Author

Adams, David, Tournev, Ivailo L., Taylor, Mark S., Coelho, Teresa, Planté-Bordeneuve, Violaine, Berk, John L., González-Duarte, Alejandra, Gillmore, Julian D., Low, Soon-Chai, Sekijima, Yoshiki, Obici, Laura, Chen, Chongshu, Badri, Prajakta, Arum, Seth M., Vest, John, and Polydefkis, Michael

Subjects
CLINICAL trials, AMYLOIDOSIS, PATIENT safety, POLYNEUROPATHIES
Abstract

The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months. HELIOS-A enrolled 164 patients (vutrisiran, n = 122; patisiran reference group, n = 42); external placebo, n = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10−12), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths. Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile. NCT03759379 [ABSTRACT FROM AUTHOR]

Published
2023
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47. A novel substitution of proline (P32L) destabilises β2-microglobulin inducing hereditary systemic amyloidosis

Author

Prokaeva, Tatiana, primary, Joshi, Tracy, additional, Klimtchuk, Elena S., additional, Gibson, Victoria M., additional, Spencer, Brian, additional, Siddiqi, Omar, additional, Nedelkov, Dobrin, additional, Hu, Yueming, additional, Berk, John L., additional, Cuddy, Sarah A. M., additional, Dasari, Surendra, additional, Chiu, April, additional, Choate, Lauren A., additional, McPhail, Ellen D., additional, Cui, Haili, additional, Chen, Hui, additional, Burks, Eric J., additional, Sanchorawala, Vaishali, additional, and Connors, Lawreen H., additional

Published
2022
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49. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial

Author

Adams, David, Tournev, Ivailo L., Taylor, Mark S., Coelho, Teresa, Planté-Bordeneuve, Violaine, Berk, John L., González-Duarte, Alejandra, Gillmore, Julian D., Low, Soon-Chai, Sekijima, Yoshiki, Obici, Laura, Chen, Chongshu, Badri, Prajakta, Arum, Seth M., Vest, John, and Polydefkis, Michael

Abstract

The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months. HELIOS-A enrolled 164 patients (vutrisiran, n = 122; patisiran reference group, n = 42); external placebo, n = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10−12), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths. Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile. NCT03759379

Published
2022
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