Golodirsen (Vyondys 53™), an antisense oligonucleotide of the phophorodiamidate morpholino oligomer (PMO) subclass designed to induce exon 53 skipping, has been developed by Sarepta Therapeutics for the treatment of Duchenne muscular dystrophy (DMD). In December 2019, intravenous golodirsen received its first global approval in the USA for the treatment of DMD in patients with a confirmed mutation of the DMD gene that is amenable to exon 53 skipping, based on positive results from a phase I/II clinical trial. Golodirsen is in phase III clinical development for the treatment of DMD worldwide. This article summarizes the milestones in the development of golodirsen leading to this first approval for DMD.
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Verhaart IEC, Aartsma-Rus A. Therapeutic developments for Duchenne muscular dystrophy. Nat Rev Neurol. 2019;15(7):373–86.
Messina S, Vita GL. Clinical management of Duchenne muscular dystrophy: the state of the art. Neurol Sci. 2018;39(11):1837–45.
Sarepta Therapeutics. Sarepta Therapeutics announces FDA approval of Vyondys 53™ (golodirsen) injection for the treatment of Duchenne muscular dystrophy (DMD) in patients amenable to skipping exon 53 [media release]. 12 Dec 2019.
Sarepta Therapeutics. Sarepta Therapeutics receives Complete Response Letter from the US Food and Drug administration for golodirsen new drug application [media release]. 19 Aug 2019.
US Food & Drug Administration. FDA grants accelerated approval to first targeted treatment for rare Duchenne muscular dystrophy mutation [media release]. Dec 12 2019.
Sarepta Therapeutics. Vyondys 53™ (golodirsen) injection, for intravenous use. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211970s000lbl.pdf. Accessed 12 Dec 2019.
Sarepta Therapeutics. Sarepta Therapeutics enters into collaboration for the development of additional exon-skipping product for Duchenne muscular dystrophy [media release]. 26 Nov 2012.
Sarepta Therapeutics, University of Western Australia. Sarepta therapeutics and University of Western Australia announce exclusive worldwide licensing agreement for exon-skipping program in duchenne muscular dystrophy [media release]. 11 Apr 2013.
US Securities and Exchange commission. First amendement to license agreement 2016. https://www.sec.gov/. Accessed 9 Jan 2020.
Sarepta Therapeutics. Sarepta Therapeutics announces favorable USPTO decisions in exon 51 and exon 53 composition of matter patent interference cases against BioMarin Pharmaceutical [media release]. 20 Sep 2016.
Sarepta Therapeutics. Sarepta Therapeutics and BioMarin Pharmaceutical Inc. announce execution of a global settlement and a license agreement resolving exon skipping patent litigation [media release]. 18 Jul 2017.
Muntoni F, Frank DE, Morgan J, et al. Golodirsen induces dystrophin expression [abstract no. S-5 and presentation]. J Clin Neuromuscul Dis. 2018;19(3):173.
Sazani P, Charleston JS, Shanks C, et al. Pharmacokinetic evaluation of eteplirsen, SRP-4045, and SRP-4053; three phosphorodiamidate morpholino oligomers (PMOs) for the treatment of patients with Duchenne muscular dystrophy (DMD) [abstract no. PP09.5-2350]. Eur J Paediatr Neurol. 2015;19(Suppl 1):S66.
Frank DE, Mercuri E, Servais L, et al. Golodirsen treatment induces dystrophin expression and is well-tolerated in eligible patients with Duchenne muscular dystrophy [abstract no. 8]. Muscle Nerve. 2019;60(Suppl 2):S7.
Scaglioni D, Catapano F, Ellis M, et al. Novel high-throughput digital analysis to quantify the amount of functional sarcolemmal dystrophin and myofibre regeneration in Duchenne muscular dystrophy clinical trial samples (exon 53 skipping with golodirsen) [abstract no. P.146]. Neuromuscul Disord. 2019;29(Suppl 1):S91.
Tsai K, McSherry C, Leffler M, et al. Physical function of eteplirsen- and golodirsen-treated Duchenne muscular dystrophy patients: methodology of the longitudinal evaluation of exon-skipping–amenable patients (LEAP) sudy [poster presentation]. In: Muscular Dystrophy Association Clinical and Scientific Conference 2019.
The preparation of this review was not supported by any external funding.
Conflict of interest
During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Young-A Heo is a salaried employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.
Enhanced material for this AdisInsight Report can be found at https://doi.org/10.6084/m9.figshare.11788788.
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