MEDICATION INSIGHTS:

givinostat (Duvyzat™)
delandistrogene moxeparvovec-rokl (Elevidys^®)

2024 updates: Givinostat (Duvyzat™) was approved by the United States (U.S.) Food and Drug Administration (FDA) in March 2024 for the treatment of Duchenne muscular dystrophy (DMD) in patients ages six years and older. Givinostat is the first nonsteroidal drug approved to treat patients with all genetic variants of DMD.¹ It is a histone deacetylase (HDAC) inhibitor that works by targeting pathogenic processes to reduce inflammation and loss of muscle.¹

Delandistrogene moxeparvovec-rokl (Elevidys^®) is a gene therapy for the treatment of DMD that was originally approved via accelerated pathway by the FDA in June 2023 for ambulatory individuals ages four to five years with DMD with a confirmed mutation in the DMD gene. The FDA expanded the approval of delandistrogene moxeparvovec-rokl in June 2024 via traditional pathway to include ambulatory and via accelerated pathway to include nonambulatory individuals ages four years and older with DMD with a confirmed mutation in the DMD gene.²

Prime Therapeutics sought insight from key opinion leader(s) (KOL) within our Expert Clinical Network (ECN) who specialize in pediatric neurology. This month’s newsletter summarizes KOL feedback on a wide range of updates in DMD, including the aforementioned new treatment option, expanded indication, and more.

Efficacy and safety

To date, the use of corticosteroids in DMD patients is considered standard of care. However, not every patient tolerates corticosteroids well, including more recently approved agents such as deflazacort (Emflaza^®) and vamorolone (Agamree^®). Givinostat is the first nonsteroidal drug with an approved indication to treat patients with all genetic variants of DMD. As part of the standard of care, stable corticosteroid use was an inclusion criterion for the clinical trial that led to the FDA approval of givinostat. While the clinical trial for givinostat was performed in ambulatory patients, there is an expectation that the drug would have similar benefits for nonambulatory patients. The pathophysiologic process remains the same in both groups, as the loss of ambulation is only a point in the patient’s progressive muscle strength decline.

Regarding safety concerns with the use of givinostat with other DMD treatment options, there are no known safety concerns at this time with the use of givinostat in patients who received delandistrogene moxeparvovec-rokl or who are currently receiving exon-skipping therapy such as eteplirsen (Exondys 51™), golodirsen (Vyondys 53™), viltolarsen (Viltepso^®) and casimersen (Amondys 45™).

Most recently, delandistrogene moxeparvovec-rokl received an expanded approval from the FDA. This is a gene therapy treatment option for DMD that was previously approved for use in ambulatory patients ages four to five years. In ongoing clinical trials, meaningful benefits were tested and seen in patients with ages beyond the original age group and those with disease progression. The approved indication was therefore expanded to encompass additional patients who could achieve the added benefits of this therapy.

While it is encouraging to see very good levels of microdystrophin expression as well as proper localization in the treated subjects in the clinical trials for delandistrogene moxeparvovec-rokl, the clinical significance remains less clear. The microdystrophin produced by gene therapy is unlike any of the truncated dystrophins created through exon-skipping. This makes a comparison between the expression levels irrelevant. What can be said of both delandistrogene moxeparvovec-rokl gene therapy and exon-skipping options though, is that greater benefit is realized if the therapy is given early in the disease, while benefit decreases when given at later, more severe stages of the disease.

As the newest therapy option, there is some concern around the clinical justification of gene therapy after treatment failure with an exon-skipping therapy. This could potentially influence an increase in exon-skipping failures and drive eligible patients toward delandistrogene moxeparvovec-rokl, increasing the overall demand for this treatment. The side effect profile of gene therapy is unlikely to deter the majority of patients from this treatment option. Similar to the demand seen for exon-skipping therapy after approval, the FDA approval of delandistrogene moxeparvovec-rokl will likely drive increasing demand for gene therapy.

Our Expert Clinical Network (ECN) is part of our value-based approach to medical and pharmacy benefit management where customers have access to over 175 national and world-renowned key opinion leaders (KOLs) in multiple disease categories. These experts assist clients with challenging prior authorization case reviews, peer-to-peer discussions, drug policy development and formulary guidance. Our ECN supports health plans and providers to make more informed decisions, leading to positive patient outcomes and avoidance of inappropriate care.

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