https://m2.mtmt.hu/ hun 2026-05-26 12:01 JournalArticle 35598424 VALIDATED true Funding Agency and Grant Number: Stealth BioTherapeutics, Newton, MA; Stealth BioTherapeutics Funding text: Trial funded by Stealth BioTherapeutics, Newton, MA. All payments from Stealth BT were directly pertaining to travel for investigator meetings and the conduct of this clinical trial. Manuscript preparation and submission was also funded by Stealth BioTherapeutics. 0 false 2026-05-24T11:54:46.162+0000 2024-12-03T07:48:18.976+0000 2024-11-25T09:34:07.492+0000 true 10015544 Csajbók Edit /api/admin/10015544 Admin true 10015544 2026-01-20T14:04:53.920+0000 2026-01-20T14:04:53.920+0000 2024-12-03T07:48:18.984+0000 true 10080205 Szalóky-Siki Ágnes /api/admin/10080205 Admin true true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000359 Study Group true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000359 Sokszerzős vagy csoportos szerzőségű szakcikk SubType 104 true 10000359 true 1 /api/category/1 Category true 1 Karaa, Amel Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy a post hoc analysis of the MMPOWER-3 trial. true true /api/journal/10007208 REVIEWED true false 10007208 false 10007208 true 1750-1172 1750-1172 Journal FOREIGN 19 1 431 431 12 2024 As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing nuclear DNA (nDNA) pathogenic variants receiving elamipretide experienced an improvement in the six-minute walk test (6MWT), while the cohort of subjects with mitochondrial DNA (mtDNA) pathogenic variants showed no difference versus placebo. These published findings prompted additional genotype-specific post hoc analyses of the MMPOWER-3 trial. Here, we present these analyses to further investigate the findings and to seek trends and commonalities among those subjects who responded to treatment, to build a more precise Phase 3 trial design for further investigation in likely responders.Subjects with mtDNA pathogenic variants or single large-scale mtDNA deletions represented 74% of the MMPOWER-3 population, with 70% in the mtDNA cohort having either single large-scale mtDNA deletions or MT-TL1 pathogenic variants. Most subjects in the nDNA cohort had pathogenic variants in genes required for mtDNA maintenance (mtDNA replisome), the majority of which were in POLG and TWNK. The mtDNA replisome post-hoc cohort displayed an improvement on the 6MWT, trending towards significant, in the elamipretide group when compared with placebo (25.2 ± 8.7 m versus 2.0 ± 8.6 m for placebo group; p = 0.06). The 6MWT results at week 24 in subjects with replisome variants showed a significant change in the elamipretide group subjects who had chronic progressive external ophthalmoplegia (CPEO) (37.3 ± 9.5 m versus - 8.0 ± 10.7 m for the placebo group; p = 0.0024). Pharmacokinetic (exposure-response) analyses in the nDNA cohort showed a weak positive correlation between plasma elamipretide concentration and 6MWT improvement.Post hoc analyses indicated that elamipretide had a beneficial effect in PMM patients with mtDNA replisome disorders, underscoring the importance of considering specific genetic subtypes in PMM clinical trials. These data serve as the foundation for a follow-up Phase 3 clinical trial (NuPOWER) which has been designed as described in this paper to determine the efficacy of elamipretide in patients with mtDNA maintenance-related disorders.Class I CLINICALTRIALS.NCT03323749. 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<img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" >Karaa Amel ✉ </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10002781"><a href="/gui2/?type=authors&mode=browse&sel=10002781" target="_blank">Molnar Maria Judit (<span class="authorship-author-name">Molnár Mária Judit</span> <span class="authorAux-mtmt"> Neurológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Genomikai Medicina és Ritka Betegségek Intézete</span> ;&nbsp;&nbsp;&nbsp; et al. (34) </div> <div class="autype autype-11"> Kollaborációs közreműködő: <span class="author-name" mtid="10040725"><a href="/gui2/?type=authors&mode=browse&sel=10040725" target="_blank">Grosz Zoltan (<span class="authorship-author-name">Grosz Zoltán</span> <span class="authorAux-mtmt"> Neurológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Genomikai Medicina és Ritka Betegségek Intézete</span> </div> <div class="autype autype-29"> Kollaborációs szervezet: <span class="author-affil">MMPOWER-3 Trial Investigators</span> </div> <div><a target="_blank" href="/api/publication/35598424?labelLang=hun">Összes szerző</a></div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;35598424" target="_blank">Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy : a post hoc analysis of the MMPOWER-3 trial..</a></div> <div> <span class="journal-title">ORPHANET JOURNAL OF RARE DISEASES</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1750-1172">1750-1172</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1750-1172">1750-1172</a>)</span>: <span class="journal-volume">19</span> <span class="journal-issue">1</span> <span class="page"> Paper 431. 12 p. </span> <span class="year">(2024)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="10.1186/s13023-024-03421-5" target="_blank" href="https://doi.org/10.1186/s13023-024-03421-5"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="001375324200001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001375324200001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85210014772" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85210014772"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="39574155" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=39574155&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Genetics (clinical)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Medicine (miscellaneous)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Pharmacology (medical)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;Q1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 10</span> | Független: 7 | Függő: 3 | Nem jelölt: 0 | WoS jelölt: 10 | Scopus jelölt:&nbsp;10 | WoS/Scopus jelölt:&nbsp;10 | DOI jelölt:&nbsp;10 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;35598424&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 2 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 35598424</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Sokszerzős vagy csoportos szerzőségű szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">PubMed XML</span> </div> <div class="funder"> (HUN-REN Hungarian Research Network), (National Research and Innovation Office) </div> <div class="lastModified">Utolsó módosítás: 2024.12.03. 08:48 Szalóky-Siki Ágnes (SE_KK_Admin5_SZSA, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Funding Agency and Grant Number: Stealth BioTherapeutics, Newton, MA; Stealth BioTherapeutics Funding text: Trial funded by Stealth BioTherapeutics, Newton, MA. All payments from Stealth BT were directly pertaining to travel for investigator meetings and the conduct of this clinical trial. Manuscript preparation and submission was also funded by Stealth BioTherapeutics.</pre> </div></div>