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#apaperaday: Characteristics of Patients Receiving Novel Muscular Dystrophy Drugs in Trials vs Routine Care

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Characteristics of Patients Receiving Novel Muscular Dystrophy Drugs in Trials vs Routine Care

#apaperaday from Erlangen where I will present in the Tom Wahlig HSP meeting later today. The pick is from @JAMANetworkOpen by Hong et al on the characteristics of Duchenne patients commercially treated with exon skipping drugs doi 10.1001/jamanetworkopen.2023.53094

The FDA approved eteplirsen in 2016 based on its ability to skip exon 51 to restore the production of partially functional dystrophin. The approach is mutation specific and other exon skipping drugs followed: golodirsen, viltolarsen, and casimersen.

The drugs have several other similarities 1. Approvals were only based on low levels of dystrophin restoration and functional evidence of treatment needs to be collected in ongoing trials. 2. Drugs are expensive with an estimated cost of 300k$ but real costs being higher.

Authors here used databases of public and private insurers to study the characteristics of patients using these drugs in clinical trials and in regular care. Patients in clinical trials were younger than those treated in the care setting: 8.5 years vs 12-13.7 years average.

Patients treated with regular care also had more advanced disease (as expected from age finding). Most patients treated in regular care were white (90%), which is much higher than the percentage of white people in the insurance databases.

Almost all patients treated were receiving eteplirsen. Annual costs for different insurance databases were 400-600 k$ per patient per year. 1/3 of patients stopped eteplirsen treatment after 7 months, especially patients in later disease stages.

For these later-stage patients, costs were also higher with some over 1.3 million per patient per year. Authors discuss that these drugs aim to slow down disease progression and this may be more difficult to observe in later stages.

Furthermore, they stress that evidence that these drugs slow down progression in early stages from trials is still lacking. The high discontinuation rate in later-stage patients may be due to safety concerns or other health issues authors speculate.

Personally, I think the burden of weekly intravenous infusions is high especially for more advanced patients and the potential therapeutic effects are more slowly visible than in an early stage. So they may have concluded the time and burden were not worth it.

Authors discuss the high costs combined with high discontinuation rates poses a financial burden for the healthcare system as each dollar can be spent only once. Furthermore, they give the limitations of their study: they cannot check whether patients treated had eligible mutations.

Also, patients who took a treatment break were counted as a discontinuation. Furthermore, it is possible that some patients were recorded in different databases and so far almost all data is from eteplirsen.

So more data is needed: real-world evidence of patients on treatment in a care setting and of course the results of the confirmatory studies in the clinical trial setting.