Yung Chyung, MD

"We will continue to look further into the ambulatory type 3 SMA data from the TOPAZ trial as we believe there’s a potential signal there. There’s a lot of work ahead of us, but we’re excited about the progress and look forward to finding updates as they become available.”

Following the completion of the phase 2 TOPAZ clinical trial (NCT039215128), investigators concluded that the results shown for apitegromab (Scholar Rock) in patients with spinal muscular atrophy (SMA) warrant a phase 3 study. Apitegromab, a muscle-directed therapy that serves as a complimentary approach to approved 

upregulator therapies, was proven to be safe and effective in treating multiple different SMA populations, including ambulatory SMA type 2, ambulatory SMA type 3, and nonambulatory SMA type 3.

In addition to milestones gained throughout the study, the data also suggested that increases in Hammersmith Functional Motor Scale Expanded (HFMSE) scores were attributable to the therapy, as demonstrated by no correlation between duration of prior nusinersen (Spinraza; Biogen) treatment and change in HFMSE. 

, chief medical officer, Scholar Rock, claimsthat the company is ecstatic about the progress of apitegromab, and has intentions of expanding its broad range to patients with SMA type 1.

Chyung provided additional background on the parameters of the phase 3 trial, topline end points being evaluated, and regulatory outlook pending the trial’s success. He also noted that apitegromab has already received regulatory feedback in terms of fast track and prime designations.

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The chief medical officer of Scholar Rock discussed the upcoming phase 3 trial for apitegromab in SMA and whether a successful trial would warrant FDA submission. 

The Outlook for Apitegromab and Its Phase 3 Trial: Yung Chyung, MD

"Given that most patients are already suffering from substantial motor function deficits at the time of diagnosis, there’s a big need here to address this challenge. Even for patients who started 

therapies earlier in life, the treatments appear to be far from curative.”

Scholar Rock’s apitegromab, a muscle-directed therapy designed to work as a complimentary piece to upregulated previously approved treatments for patients with spinal muscular atrophy (SMA), could represent a unique and alternative approach to treating the disease. The therapy demonstrated proof-of-concept in treating ambulatory SMA type 2, ambulatory SMA type 3, and nonambulatory SMA type 3 in the recently concluded phase 2 TOPAZ clinical trial (NCT03921528).

upregulated therapies has revolutionized the way patients with SMA are treated, there still remains a number of unmet needs. In particular, those who are treated late or who have missed the “window” of treatment optimization and may not receive the same benefits from these therapies compared to those treated with earlier intervention. Yung Chyung, MD, chief medical officer, Scholar Rock, told 

that the SMA treatment landscape is lacking an alternative complementary therapy like apitegromab.

Listen to Chyung’s comments on the current unmet needs for patients within the SMA community, the importance for earlier diagnosis, and why all patient populations, including those who’ve missed early intervention, should be accounted for when creating therapeutic options.

The chief medical officer of Scholar Rock discussed the greatest areas of concern for patients with SMA and why most of these issues exist in the diagnostic stage.

Identifying Unmet Needs in Spinal Muscular Atrophy: 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 

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 

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 

that the company eventually plans to explore apitegromab on top of other 

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.

The chief medical officer of Scholar Rock detailed the additive benefits apitegromab has in treating SMA when used with previously approved nusinersen. 

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

“All in all, we are quite enthusiastic about advancing our program of apitegromab and further investigating the safety and efficacy of this molecule towards our aspiration of transforming the care of patients with SMA.”

Data from the phase 2 TOPAZ clinical trial (NCT03921528) presented at the 2021 Cure SMA Research & Clinical Care Meeting, June 9-11, showed that treatment with apitegromab (SRK-015; Scholar Rock) further demonstrated proof-of-concept in patients with spinal muscular atrophy (SMA) types 2 and 3. A majority of the 23 patients (57%; n = 13) with ambulatory type 3 SMA who received a 20-mg/kg dose monotherapy of apitegromab in conjunction with nusinersen (Spinraza; Biogen) across cohort 1 maintained or improved their motor function, as reflected by a greater than 0-point change from baseline in Revised Hammersmith Scale.

No new safety signals for apitegromab were identified in the 12-month topline analysis, with headache, pyrexia, upper respiratory tract infection, cough, and nasopharyngitis rounding out the most frequently reported treatment-emergent adverse events. Findings from the study helped advance the drug into a pivotal phase 3 trial, which is expected to launch by the end of 2021.

Yung Chyung, MD, chief medical officer, Scholar Rock, sat down with 

to provide more insight on the results, as well as to discuss why there is palpable buzz surrounding the drug and its clinical pathway.

Scholar Rock announces positive 12-month top-line results from the TOPAZ phase 2 clinical trial evaluating apitegromab in patients with type 2 and type 3 spinal muscular atrophy (SMA). News release. April 6, 2021. Accessed July 1, 2021. 

https://investors.scholarrock.com/news-releases/news-release-details/scholar-rock-announces-positive-12-month-top-line-results-topaz

The chief medical officer of Scholar Rock discussed topline results from the phase 2 TOPAZ study of apitegromab in patients with spinal muscular atrophy.

Yung Chyung, MD

Articles

The Outlook for Apitegromab and Its Phase 3 Trial: Yung Chyung, MD

Identifying Unmet Needs in Spinal Muscular Atrophy: Yung Chyung, MD

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

Apitegromab’s Potential in Treating SMA: Yung Chyung, MD

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