September 21, 2020
inThought Research and Bloomberg Intelligence were joined by expert speakers in the field of Spinal Muscular Atrophy (SMA), Adrian Krainer, PhD, and Thomas Crawford, MD, to discuss the recent approval of the third disease-modifying therapy, Evrysdi. Key insights provided include:
- Patients currently stable with Zolgensma or Spinraza will likely not be switched to Evrysdi. Due to a lack of long-term data, Dr. Crawford described a “wait and see” approach for the new drug.
- The speakers questioned whether an oral drug will reduce drug adherence in patients treated with Evrysdi.
- The main barrier to treatment with both Zolgensma and Spinraza is access. Evrysdi will be prescribed to patients without access to a hospital setting, not eligible for the one-time gene therapy Zolgensma, and patients with spinal deformities, making Spinraza’s intrathecal injections challenging.
- There is a momentum with newborns being treated with Zolgensma, and parents are drawn to the safe one-time treatment. Although, there is a concern regarding Zolgensma’s safety in older patients (intrathecal injections).
- Both speakers agreed that a medical device, such as an implantable drug pump for Spinraza treatment, would allow it to better compete with the new therapies.
- All three treatments have comparable efficacy and safety; a biomarker, such as measuring neurofilament accumulation, should be implemented to accurately and sensitively measure outcomes of the different treatment options.
- Additionally, the speakers find it doubtful the new oral drug will drive down the price of alternative therapies, as there is not a substantial price difference when a patient peaks the weight-adjusted pricing.
While it may be tempting to compare Evrysdi with Spinraza and Zolgensma, there have been no head-to-head clinical studies, nor any plans for those studies. Everysdi has attractive features, it is safe, it has a broad label, and it is oral. But what has the potential of being the most significant factor distinguishing Evrysdi from the other two therapies is its systemic delivery. It is designed to target every cell in the body, and there is increasing evidence suggesting that SMA is a body wide disease. However, it comes with the caveat that the long-term safety profile of this systemically delivered therapy is unknown. Side-effects in systemically delivered treatments could be associated with more risks than targeted treatments.
In the absence of head-to-head trials, predictive molecular biomarkers, and long-term data, future comparisons will rely on real-world data from SMA registry studies. Collecting and analyzing information such as treatment response, age, disease type/severity, and genetic backgrounds will allow physicians to generate comparisons and indicate treatment.
Source: SMA inThought Bloomberg Webinar