Real-World Challenges in DMD PMO Treatment

For patients with Duchenne muscular dystrophy (DMD), real-world treatment patterns for phosphorodiamidate morpholino oligomer (PMO) therapies showed high adherence rates but identified significant challenges in using claims data to assess treatment effectiveness.¹

Published in Advances in Therapy, this research underscores both the promise of PMO therapies and the complexities of monitoring their use in real-world settings.

The retrospective study analyzed commercial and Medicaid claims data from 133 male patients with DMD who received PMO treatments—eteplirsen, golodirsen, viltolarsen, and casimersen—between 2018 and 2021. The average patient age was 14 years, with treatment durations spanning a median of 546 days.

PMO therapies target specific genetic mutations in DMD by skipping affected exons to enable production of dystrophin. | Image credit: natali_mis – stock.adobe.com

The findings revealed that 55.6% of patients maintained continuous treatment without gaps exceeding 30 days, while 44.4% experienced such interruptions. Among those with gaps, 75.5% resumed treatment within a year, with a median time to resumption of 64 days. Overall, the median proportion of days covered (PDC) across the study population was 83.4%, highlighting the consistency of treatment patterns despite gaps in claims.

“Most patients had continuous PMO claims coverage, and most patients with a gap in PMO claims had a subsequent PMO claim,” the authors found. “Nonetheless, the observed persistence may have been underestimated given shortcomings of claims data and payer coverage considerations.”

PMO therapies like eteplirsen target specific genetic mutations in DMD by skipping affected exons to enable production of dystrophin, a protein critical for muscle health.² These treatments are typically administered weekly via intravenous infusion, often at home for patients with commercial insurance in this study.¹ About half (50.3%) of infusions occurred in patients’ homes, with substantially more in-home PMO infusions among commercially insured patients (88.9%) than patients with Medicaid (11.3%). Importantly, 44.3% of claims in this study were missing information on the site of PMO infusion.

Compared with commercially insured patients, Medicaid patients were also more likely to experience gaps in treatment (36% vs 29.3%) and had a slightly lower likelihood of resuming therapy within a year. These differences may reflect the administrative hurdles associated with Medicaid authorizations, including frequent reauthorization requirements that can disrupt treatment continuity.

Real-world adherence, discontinuation, and persistence with treatments are key metrics for payers and providers, offering insights into a therapy's potential effectiveness, safety, and tolerability. However, the researchers emphasized that claims data alone should not be used to draw definitive conclusions about these aspects.

“While the accuracy of assessing adherence and persistence to oral treatments using administrative data has been investigated, the ability to accurately observe real-world treatment patterns for infused treatments using administrative data is unclear,” they noted.

One notable limitation was the difficulty in differentiating between missed infusions and administrative gaps. For example, site-of-administration data was only provided for HCPCS codes and was not available in 82.9% of Medicaid claims, raising questions about whether treatments were delivered but not properly coded. Additionally, the weight-based dosing of PMO therapies introduces variability in claims, as patient weight—critical for calculating doses—is not captured in administrative data.

Despite these challenges, the study authors emphasized the importance of understanding real-world treatment patterns to improve access and continuity of care. Given the complex reimbursement landscape in the US, understanding treatment patterns is essential for optimizing patient outcomes and ensuring equitable access to precision genetic medicines.

Reauthorization delays and administrative processes can significantly impact access to life-saving therapies, with the authors calling for improvements in claims coding practices and better integration of clinical and administrative data to provide a clearer picture of real-world treatment effectiveness.

References

1. Klimchak AC, Signorovitch J, Innis B, Laverty CG, Gooch K. Assessment of phosphorodiamidate morpholino oligomer treatment patterns for patients with Duchenne muscular dystrophy: a MarketScan claims analysis. Adv Ther. Published online November 11, 2024. doi:10.1007/s12325-024-03044-z
2. Leveraging RNA technology to treat rare disease. Sarepta Therapeutics. Accessed November 25, 2024. https://www.sarepta.com/science/rna-platform