It remains a matter of curiosity how much Creatine Kinase (CK) levels decrease, NSAA score and normal dystrophin levels increase in children with DMD who receive ELEVIDYS (delandistrogene moxeparvovec-rokl), one of the world’s most expensive therapies developed by Sarepta Therapeutics for Duchenne muscular dystrophy.
ELEVIDYS (delandistrogene moxeparvovec-rokl), developed by Sarepta Therapeutics, is a one-time AAV (adeno-associated virus) gene therapy approved in June 2023 in the U.S. for ambulatory pediatric DMD patients aged 4-5 years, and later expanded. >>> investorrelations.sarepta.com
It is designed to deliver a gene encoding a micro-dystrophin protein (about 138 kDa vs the normal ~427 kDa dystrophin) into muscle cells. >>> PubMed
In DMD, the absence or severe deficiency of dystrophin causes muscle cell damage; markers such as creatine kinase (CK) rise as muscle fibers deteriorate. Therefore, two surrogate biomarkers considered in Duchenne muscular dystrophy are:
- CK levels, as a marker of muscle damage/leakage into blood > What is creatine kinase?
- Dystrophin (or in this case micro-dystrophin) expression levels in muscle tissue
The core questions about Creatine Kinase (CK), Dystrophin Level and NSAA Score in Elevidys Gene Therapy:
- After ELEVIDYS therapy in children with DMD, by how much do CK levels decrease, and by how much does dystrophin/micro-dystrophin increase?
- What proportion of normal human dystrophin is represented by the microdystrophin level achieved after treatment?
Table of Contents
How much micro-dystrophin is produced by Elevidys?
According to information published on Elevidys’ official website, across all clinical trials, participants produced an average of 34% to 51% of ELEVIDYS micro-dystrophin after 3 months of treatment. But it does not specify how much normal dystrophin this amount equates to.
Check out the dystrophin increase in Vyondys 53 exon skipping therapy.
How much did the NSAA score increase in children receiving Elevidys?
What is North Star Ambulatory Assessment (NSAA)
Total score 0 – 34 with a higher score denoting a higher level of function. It includes two timed tests. Timed rise from floor (RFF) and timed 10 metre walk / run test (10MWR). Validated and regularly used in clinical trials as well as clinic. Read More: NSAA
According to information published on Elevidys’ official website, there was a 2.6-point increase in the 34-point NSAA test in children who received gene therapy and a 1.9-point increase in children who did not receive gene therapy. This means that the children who did not receive Elevidys gene therapy also experienced improvement. >>> Elevidys
According to the EMA report, this increase was only 0.65 points. >>> DMDWarrior
What level of improvement was observed in children who were administered Elevidys?
- Those who received ELEVIDYS were able to get up from the floor 0.64 seconds faster than those on placebo (no ELEVIDYS) after 1 year (on average) >>> Efficacy results for SRP-9001 (Elevidys)
- Those who received ELEVIDYS were able to walk/run 10 meters 0.42 seconds faster than those on placebo (no ELEVIDYS) after 1 year (on average) >>> Results in ambulatory
What we do know about micro-dystrophin increase
- According to the approval summary, the FDA found that ELEVIDYS increased expression of the micro-dystrophin protein in skeletal muscle of treated patients. >>> investorrelations.sarepta.com
- A review article (preprint) states: “After 48 weeks, treated patients demonstrated a mean micro-dystrophin expression of ~28 % on western blot.” >>> preprints.org
- An announcement about the EMBARK study states, ‘In patients treated in Part 1, biopsies taken 64 weeks after dosing showed consistent and sustained expression of ELEVIDYS micro-dystrophin compared to week 12 biopsies, as measured by western blot, and provide biological support for observed functional outcomes.’ However, the announcement did not disclose figures for how much micro-dystrophin was produced and how well it maintained its level over time. >>> sarepta.gcs-web.com
Thus, one available figure is approx 28% expression relative to normal (on western blot) at ~48 weeks in the treated group (in that small study). However:
- It is not always clear what “100%” means (normal healthy dystrophin levels) in that measurement.
- Functional improvement (motor endpoints) in the larger trial did not meet the primary endpoint. >>> Medscape
So, while micro-dystrophin levels do increase, the exact magnitude varies, the long-term durability is still under study, and the translation to clinical benefit remains uncertain.
What we do not yet know clearly about CK decrease
In the public regulatory documents and publications that We reviewed, there is no clearly published, robust value for how much CK (creatine kinase) levels decrease after ELEVIDYS in children with DMD. Key points:
- The FDA expansion approval statement mentions that among the totality of evidence considered were “improvement in … creatine kinase levels” among other endpoints. >>> U.S. Food and Drug Administration
- However, We did not find a published figure such as “CK decreased by X% on average at Y weeks/months” in the peer-reviewed literature (at least in the sources accessible).
- Many of the results remain exploratory or secondary endpoints; the primary functional endpoint (NSAA) in EMBARK did not reach statistical significance (difference of ~0.65 points) at 52 weeks. >>> Medscape
Thus, while there is indication that CK levels may decline, the degree of decline (e.g., percent reduction, absolute units) is not publicly well‐characterised in multiple large studies (or at least not yet published in easily accessible form).
Why the data gap matters
- CK is a widely used biomarker in DMD to track muscle damage/leakage. A substantial drop in CK might suggest reduced ongoing muscle injury.
- Dystrophin (or micro-dystrophin) expression is a mechanistic marker: showing the therapy is doing what it is designed to do.
- But even if micro-dystrophin increases and CK decreases, the key question remains: does that translate into meaningful functional/motor benefit, longer ambulation, better quality of life?
- The fact that the large Phase 3 trial did not meet its primary motor endpoint raises caution: increase in protein expression does not automatically guarantee large functional gains. >>> Medscape
- Regulatory agencies such as the European Medicines Agency (EMA) have been more skeptical: the EMA’s CHMP recommended not to grant marketing authorisation for Elevidys in July 2025, citing insufficient functional benefit despite micro-dystrophin production. >>> DMDWarrior
What this means for children/families and clinicians
- If you are a family or clinician considering ELEVIDYS, it’s realistic to know that micro-dystrophin expression does increase (e.g., ~28% in one study) but the translation into clear, meaningful functional benefit in long-term real-world usage is still under verification.
- Since CK reduction figures aren’t clearly defined/consistently published, one should not assume that CK will drop by a particular percentage; monitoring CK remains part of research/clinical follow-up, but expectations should be tempered.
- It remains critically important to enrol in or follow the follow-up/confirmatory trials (such as EMBARK) and to monitor both muscle biomarkers (dystrophin expression, CK) and functional endpoints (ambulation, timed-tests, respiratory/cardiac status).
- Because gene therapy is one-time and very costly (initial pricing has been reported in the multi-million-dollar range in discussions) and has known safety risks (e.g., liver injury) the decision must weigh the known and unknown.
New Research about Lysosomal damage in Duchenne
Although gene therapy (delandistrogene moxeparvovec) obtained Food and Drug Administration (FDA) approval for ambulatory patients, the functional improvements for patients have fallen short of preclinical expectations. This limited clinical benefit could be attributed to several factors, including the lack of certain functional domains found in full-length dystrophin. Therefore, gene transfer may not be able to reverse all the pathological mechanisms in the muscle. Identifying specific pathological mechanisms that remain uncorrected by gene therapy and exploring combinatorial approaches with complementary treatments targeting these mechanisms are crucial. >>> Read More: Lysosomal damage is a therapeutic target in Duchenne muscular dystrophy
Real-world experience with Elevidys gene therapy report from Qatar
In this study conducted in Qatar, levels of various biomarkers (AST, ALT, CK, Troponin I and GGT) were monitored during a 30-week follow-up in eight patients receiving gene therapy for Duchenne Muscular Dystrophy (DMD). Source: Nature.com
We share with you some of the highlights of the study:
ALT and AST Levels
ALT and AST levels showed a decrease in the first week, followed by slight fluctuations and a minor increase around Weeks 2–3, after which a stabilization trend was observed from Week 4 onward. From Week 14, younger patients exhibited a gradual rise, peaking close to week 26 before returning to the initial post-infusion levels achieved around the second week.
Creatine Kinase (CK) Levels
During the follow-ups, CK demonstrated the most significant initial response, showing a sharp decrease of 44.1% in the first week. Levels continued to decline, reaching their lowest point around Week 4. However, CK levels significantly increased by 84.2% by Week 7. This pattern suggests a strong initial response to therapy, potentially reflecting muscle repair or reduced muscle damage, followed by a fluctuating phase as the body adapts.
NSAA Score
All parents reported positive functional changes within two months of receiving gene therapy, though four out of five expressed concerns about weight gain following treatment. One patient remained non-ambulatory and could not be timed for the 10MWT or perform a floor rise, while among the others, one demonstrated progressive improvement in the 10MWT speed over two months, two showed a decline, and one remained unchanged. These results, taken together with parent observations, suggest that steroid-induced weight gain may be affecting patient function post gene therapy.
Further larger real-world data is required to further confirm the safety and efficacy of Delandistrogene moxeparvovec for treatment of DMD patients.
Learn More: NSAA Alone Is Not Enough: Why Creatine Kinase (CK), AST, ALT, and Dystrophin Levels Should Be Public
Conclusion
- Yes, treatment with ELEVIDYS results in increased micro-dystrophin expression in muscle (with numbers such as ~28% in one study).
- The degree of CK reduction is not yet well-publicised or robustly characterised in peer-reviewed, large-scale studies—so it remains a “matter of curiosity,”.
- The long-term functional benefit remains under verification, meaning that biomarker improvements (dystrophin up, CK possibly down) are encouraging but not yet definitive guarantees of improved motor outcomes.
- As additional data from confirmatory trials and real-world registries emerge, we expect to see more granular numbers for CK reduction, durably sustained dystrophin/micro-dystrophin, and the correlation to motor function—and that will help families and clinicians make more informed decisions.
Learn More: Frequently Asked Questions About Elevidys
