Treating SMA Using a Layered Therapy Approach: Yung Chyung, MD

"Broadly speaking, many diseases involve complex biologies with very severe disease manifestations. To tackle these challenging problems, it makes sense that the overall research and development field is heading towards these integrative approaches where it’s not just 1 therapeutic tool by itself.”

The treatment landscape for patients with spinal muscular atrophy (SMA) includes SMN upregulators such as nusinersen (Spinraza; Biogen), risdiplam (Evrysdi; Roche/Genentech) and onasemnogene abeparvove-xiox (Zolgensma; Novartis). Apitegromab, an investigational muscle directed therapy designed by Scholar Rock, is aimed at complimenting these SMN upregulators by focusing on specifically improving motor function.

In the phase 2 TOPAZ clinical trial (NCT03921528), apitegromab was evaluated in cohorts of patients with nonambulatory type 2 SMA, nonambulatory type 3 SMA, and ambulatory type 3 SMA. Improvements in Hammersmith Functional Motor Scale Expanded (HFMSE) scores further demonstrated the investigational agent’s proof-of-concept when used as a monotherapy in conjunction with nusinersen. The duration of prior nusinersen treatment was also not correlated with HFMSE increase as patients were already in the chronic maintenance phase of treatment at enrollment.

Yung Chyung, MD, chief medical officer, Scholar Rock, told NeurologyLive that the company eventually plans to explore apitegromab on top of other SMN upregulators, as well as gene therapy. Chyung sat down to discuss the reasoning behind the trial design and why it speaks to the general direction precision medicine is going with using layered approaches.