Delandistrogene moxeparvovec

Delandistrogene moxeparvovec
Clinical data
Trade names	Elevidys
Other names	SRP-9001, delandistrogene moxeparvovec-rokl
AHFS/Drugs.com	Monograph
MedlinePlus	a623058
License data	US DailyMed: Delandistrogene moxeparvovec;
Routes of; administration	Intravenous infusion
ATC code	M09AX15 (WHO) ;
Legal status
Legal status	US: ℞-only;
Identifiers
CAS Number	2305040-16-6;
DrugBank	DB16802;
UNII	2P6QV2ZE52;
KEGG	D12633;

Delandistrogene moxeparvovec, sold under the brand name Elevidys, is a recombinant gene therapy used for the treatment of Duchenne muscular dystrophy.^[3] It is designed to deliver into the body a gene that leads to production of Elevidys micro-dystrophin that contains selected domains of the dystrophin protein present in normal muscle cells.^[3] It is an adeno-associated virus vector-based gene therapy that is given by intravenous infusion (slow injection into a vein).^[1]

The most commonly reported side effects include vomiting, nausea, acute liver injury, pyrexia (fever), and thrombocytopenia (abnormally low platelet count in the blood).^[3]

Delandistrogene moxeparvovec was approved for medical use in the United States in June 2023.^[3]^[4] It was developed by Sarepta Therapeutics, together with Roche, and is manufactured by Catalent.^[5]

Medical uses

Delandistrogene moxeparvovec is indicated for the treatment of ambulatory and non-ambulatory individuals four years of age and older with Duchenne muscular dystrophy with a confirmed mutation in the Duchenne muscular dystrophy gene.^[1]^[2]^[3]^[6]

Delandistrogene moxeparvovec is designed to deliver into the body a gene that leads to production of Elevidys micro-dystrophin, a shortened protein (138 kDa, compared to the 427 kDa dystrophin protein of normal muscle cells) that contains selected domains of the dystrophin protein present in normal muscle cells. FDA states that the conditional approval is based on detection of successful gene expression; evidence of clinical improvement is still pending.^[3]

In the phase 3 randomized clinical trial published in Nature Medicine, Elevidys AAV gene therapy for Duchenne muscular dystrophy failed to show statistically significant motor function improvement. The study included 125 ambulatory male patients aged 4-8 years (63 in therapy group, 62 in placebo group). Mean motor function assessment score changes were 2.57 points in the Elevidys group and 1.92 points in the placebo group, with a non-significant difference of 0.65 points at the 52-week endpoint.^[7]

History

The accelerated US Food and Drug Administration (FDA) approval of delandistrogene moxeparvovec was based on data from a randomized clinical trial that established that delandistrogene moxeparvovec increased the expression of the Elevidys micro-dystrophin protein observed in delandistrogene moxeparvovec-treated individuals aged four to five years with Duchenne muscular dystrophy.^[3]

Society and culture

Economics

Initial pricing was announced at US$3.2 million for a single treatment which is expected to last a lifetime.^[8]

References

^ ^a ^b ^c "Elevidys- delandistrogene moxeparvovec-rokl kit". DailyMed. 22 June 2023. Archived from the original on 29 August 2023. Retrieved 29 August 2023.
^ ^a ^b "Elevidys". U.S. Food and Drug Administration (FDA). 22 June 2023. Archived from the original on 5 July 2023. Retrieved 22 June 2023.
^ ^a ^b ^c ^d ^e ^f ^g "FDA Approves First Gene Therapy for Treatment of Certain Patients with Duchenne Muscular Dystrophy" (Press release). U.S. Food and Drug Administration (FDA). 22 June 2023. Archived from the original on 29 November 2023. Retrieved 22 June 2023. This article incorporates text from this source, which is in the public domain.
^ "Sarepta Therapeutics Announces FDA Approval of Elevidys, the First Gene Therapy to Treat Duchenne Muscular Dystrophy" (Press release). Sarepta Therapeutics. 22 June 2023. Archived from the original on 23 June 2023. Retrieved 22 June 2023 – via Business Wire.
^ "Catalent inks deal to manufacture Sarepta's DMD gene therapy". Archived from the original on 17 February 2023. Retrieved 23 June 2023.
^ "FDA Expands Approval of Gene Therapy for Patients with Duchenne Muscular Dystrophy". U.S. Food and Drug Administration (FDA). 20 June 2024. Archived from the original on 21 June 2024. Retrieved 21 June 2024. This article incorporates text from this source, which is in the public domain.
^ Jackson J. "$3.2 million per dose Elevidys fails to meet primary endpoint in phase 3 trial". Medical Xpress. Retrieved 25 November 2024.
^ Saltzman J, Weisman R (22 June 2023). "Cambridge biotech Sarepta wins fast-track approval for the first muscular dystrophy gene therapy". The Boston Globe. Archived from the original on 5 July 2023. Retrieved 23 June 2023.

External links

Clinical trial number NCT04626674 for "A Gene Transfer Therapy Study to Evaluate the Safety of and Expression From SRP-9001 (Delandistrogene Moxeparvovec) in Participants With Duchenne Muscular Dystrophy (DMD) (ENDEAVOR)" at ClinicalTrials.gov

[Elevidys_FDA_label-1] "Elevidys- delandistrogene moxeparvovec-rokl kit". DailyMed. 22 June 2023. Archived from the original on 29 August 2023. Retrieved 29 August 2023.

[FDA_Elevidys-2] "Elevidys". U.S. Food and Drug Administration (FDA). 22 June 2023. Archived from the original on 5 July 2023. Retrieved 22 June 2023.

[FDA_PR_20230622-3] ^ ^a ^b ^c ^d ^e ^f ^g "FDA Approves First Gene Therapy for Treatment of Certain Patients with Duchenne Muscular Dystrophy" (Press release). U.S. Food and Drug Administration (FDA). 22 June 2023. Archived from the original on 29 November 2023. Retrieved 22 June 2023. This article incorporates text from this source, which is in the public domain.

[4] "Sarepta Therapeutics Announces FDA Approval of Elevidys, the First Gene Therapy to Treat Duchenne Muscular Dystrophy" (Press release). Sarepta Therapeutics. 22 June 2023. Archived from the original on 23 June 2023. Retrieved 22 June 2023 – via Business Wire.

[5] "Catalent inks deal to manufacture Sarepta's DMD gene therapy". Archived from the original on 17 February 2023. Retrieved 23 June 2023.

[FDA_PR_20240620-6] "FDA Expands Approval of Gene Therapy for Patients with Duchenne Muscular Dystrophy". U.S. Food and Drug Administration (FDA). 20 June 2024. Archived from the original on 21 June 2024. Retrieved 21 June 2024. This article incorporates text from this source, which is in the public domain.

[7] Jackson J. "$3.2 million per dose Elevidys fails to meet primary endpoint in phase 3 trial". Medical Xpress. Retrieved 25 November 2024.

[8] Saltzman J, Weisman R (22 June 2023). "Cambridge biotech Sarepta wins fast-track approval for the first muscular dystrophy gene therapy". The Boston Globe. Archived from the original on 5 July 2023. Retrieved 23 June 2023.

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