Solid Biosciences Reports Positive Initial Clinical Data from Next-Generation Duchenne Gene Therapy Candidate SGT-003
Solid Biosciences (NASDAQ: SLDB) reported positive initial data from its Phase 1/2 INSPIRE DUCHENNE trial evaluating SGT-003, a next-generation gene therapy for Duchenne muscular dystrophy. The 90-day biopsy data from the first three participants showed an average microdystrophin expression of 110% and significant improvements in muscle health biomarkers.
The therapy has been well-tolerated in six participants dosed as of February 11, 2025, with no serious adverse events reported. Common adverse events included nausea, vomiting, fever, and transient declines in platelets. Early signals of potential cardiac benefits were observed.
The company continues enrollment, with the seventh participant dosed on February 17, 2025, and expects to dose approximately 20 total participants by Q4 2025. Solid Biosciences plans to request an FDA meeting in mid-2025 to discuss potential accelerated approval pathway for SGT-003.
Solid Biosciences (NASDAQ: SLDB) ha riportato dati iniziali positivi dal suo trial di Fase 1/2 INSPIRE DUCHENNE che valuta SGT-003, una terapia genica di nuova generazione per la distrofia muscolare di Duchenne. I dati della biopsia a 90 giorni dei primi tre partecipanti hanno mostrato un'espressione media di microdistrofina del 110% e miglioramenti significativi nei biomarcatori della salute muscolare.
La terapia è stata ben tollerata in sei partecipanti trattati fino all'11 febbraio 2025, senza eventi avversi gravi segnalati. Gli eventi avversi comuni includevano nausea, vomito, febbre e riduzioni transitorie delle piastrine. Sono stati osservati segnali precoci di potenziali benefici cardiaci.
La società continua l'arruolamento, con il settimo partecipante trattato il 17 febbraio 2025, e prevede di trattare circa 20 partecipanti totali entro il quarto trimestre del 2025. Solid Biosciences prevede di richiedere un incontro con la FDA a metà 2025 per discutere un potenziale percorso di approvazione accelerata per SGT-003.
Solid Biosciences (NASDAQ: SLDB) informó datos iniciales positivos de su ensayo de Fase 1/2 INSPIRE DUCHENNE que evalúa SGT-003, una terapia génica de nueva generación para la distrofia muscular de Duchenne. Los datos de biopsia a 90 días de los primeros tres participantes mostraron una expresión media de microdistrofina del 110% y mejoras significativas en los biomarcadores de salud muscular.
La terapia ha sido bien tolerada en seis participantes tratados hasta el 11 de febrero de 2025, sin eventos adversos graves reportados. Los eventos adversos comunes incluyeron náuseas, vómitos, fiebre y descensos transitorios en plaquetas. Se observaron señales tempranas de posibles beneficios cardíacos.
La empresa continúa con la inscripción, con el séptimo participante tratado el 17 de febrero de 2025, y espera tratar aproximadamente a 20 participantes en total para el cuarto trimestre de 2025. Solid Biosciences planea solicitar una reunión con la FDA a mediados de 2025 para discutir un posible camino de aprobación acelerada para SGT-003.
솔리드 바이오사이언스(나스닥: SLDB)는 듀센느 근이영양증을 위한 차세대 유전자 치료제 SGT-003을 평가하는 1/2상 INSPIRE DUCHENNE 임상시험의 긍정적인 초기 데이터를 보고했습니다. 첫 세 명의 참가자에 대한 90일 생검 데이터는 평균 마이크로디스트로핀 발현이 110%이며 근육 건강 바이오마커에서 상당한 개선을 보여주었습니다.
이 요법은 2025년 2월 11일 기준으로 6명의 참가자에게 잘 견디며, 심각한 부작용은 보고되지 않았습니다. 일반적인 부작용으로는 메스꺼움, 구토, 발열 및 일시적인 혈소판 감소가 포함되었습니다. 잠재적인 심장 이점의 초기 신호가 관찰되었습니다.
회사는 계속해서 등록을 진행하고 있으며, 2025년 2월 17일에 일곱 번째 참가자를 투여하였고, 2025년 4분기까지 약 20명의 총 참가자를 투여할 것으로 예상하고 있습니다. 솔리드 바이오사이언스는 2025년 중반에 SGT-003의 잠재적인 가속 승인 경로를 논의하기 위해 FDA와의 회의를 요청할 계획입니다.
Solid Biosciences (NASDAQ: SLDB) a rapporté des données initiales positives de son essai de Phase 1/2 INSPIRE DUCHENNE évaluant SGT-003, une thérapie génique de nouvelle génération pour la dystrophie musculaire de Duchenne. Les données de biopsie à 90 jours des trois premiers participants ont montré une expression moyenne de microdystrophine de 110 % et des améliorations significatives des biomarqueurs de la santé musculaire.
La thérapie a été bien tolérée chez six participants traités jusqu'au 11 février 2025, sans événements indésirables graves signalés. Les événements indésirables courants comprenaient des nausées, des vomissements, de la fièvre et des baisses transitoires des plaquettes. Des signaux précoces de bénéfices cardiaques potentiels ont été observés.
L'entreprise continue le recrutement, avec le septième participant traité le 17 février 2025, et prévoit de traiter environ 20 participants au total d'ici le quatrième trimestre 2025. Solid Biosciences prévoit de demander une réunion avec la FDA à la mi-2025 pour discuter d'un potentiel chemin d'approbation accélérée pour SGT-003.
Solid Biosciences (NASDAQ: SLDB) berichtete über positive erste Daten aus seiner Phase 1/2 INSPIRE DUCHENNE-Studie zur Bewertung von SGT-003, einer neuartigen Gentherapie für die Duchenne-Muskeldystrophie. Die 90-Tage-Biopsiedaten der ersten drei Teilnehmer zeigten eine durchschnittliche Mikrodystrophin-Expression von 110 % und signifikante Verbesserungen bei den Biomarkern der Muskelgesundheit.
Die Therapie wurde bei sechs Teilnehmern, die bis zum 11. Februar 2025 behandelt wurden, gut vertragen, ohne dass schwerwiegende Nebenwirkungen gemeldet wurden. Häufige Nebenwirkungen umfassten Übelkeit, Erbrechen, Fieber und vorübergehende Rückgänge der Thrombozyten. Frühe Hinweise auf potenzielle kardiovaskuläre Vorteile wurden beobachtet.
Das Unternehmen setzt die Rekrutierung fort, wobei der siebte Teilnehmer am 17. Februar 2025 behandelt wurde, und erwartet, bis zum vierten Quartal 2025 etwa 20 Teilnehmer insgesamt zu behandeln. Solid Biosciences plant, Mitte 2025 ein Treffen mit der FDA zu beantragen, um einen potenziellen beschleunigten Genehmigungsweg für SGT-003 zu erörtern.
- 110% average microdystrophin expression achieved in first three participants
- Significant biomarker improvements: CK (-57%), AST (-45%), ALT (-54%), LDH (-60%)
- 8% increase in mean cardiac function at Day 180 (N=2)
- No serious adverse events or unexpected reactions observed in six participants
- Enrollment progressing with 20 participants expected by Q4 2025
- Some participants experienced adverse events including nausea, vomiting, fever
- One CTCAE Grade 3 episode of thrombocytopenia occurred
- One CTCAE Grade 3 episode of prolonged fever reported
Insights
The Phase 1/2 INSPIRE DUCHENNE trial data represents a significant breakthrough in Duchenne muscular dystrophy (DMD) gene therapy. The reported 110% average microdystrophin expression across three participants is particularly noteworthy, as it exceeds the typical expression levels seen in competing gene therapies. This robust expression, validated through three different measurement methodologies, suggests superior protein production and potential therapeutic benefit.
The biomarker data is equally compelling, with substantial reductions in key muscle damage indicators:
57% reduction in serum creatine kinase45% reduction in AST54% reduction in ALT60% reduction in LDH
The safety profile is particularly impressive. Unlike other DMD gene therapies, SGT-003 has shown no serious adverse events or complement-mediated complications across six participants. Notably, no participants required additional immunomodulatory agents - a significant advantage over competing therapies that often necessitate such interventions.
The early cardiac benefits observed, including an
The inclusion of the nNOS binding domain in SGT-003's design represents a key differentiator. This feature, absent in competing therapies, may contribute to improved muscle function and cardiac benefits, potentially positioning SGT-003 as a best-in-class treatment option.
The planned FDA meeting to discuss accelerated approval pathway indicates confidence in the data package. With approximately 20 participants expected to be dosed by Q4 2025, the company is building a robust efficacy and safety database that could support regulatory submissions.
— Day 90 biopsy data reported from first 3 participants dosed in Phase 1/2 INSPIRE DUCHENNE trial —
— Average microdystrophin expression of
— Encouraging early signals of potential cardiac benefit observed —
—SGT-003 has been well-tolerated in the 6 participants dosed as of February 11, 2025, with no serious adverse events observed —
— Participant enrollment continues, with the 7th participant dosed on February 17, 2025; Company expects to dose approximately 20 total participants by Q4 2025 —
— In mid-2025, Company plans to request an FDA meeting to discuss potential accelerated approval pathway for SGT-003 —
— Company to hold a conference call today at 8:00 AM ET —
CHARLESTOWN, Mass., Feb. 18, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today announced positive initial data from the Phase 1/2 INSPIRE DUCHENNE trial evaluating SGT-003, a next-generation gene therapy product candidate intended for the treatment of Duchenne muscular dystrophy (Duchenne). Interim 90-day biopsy data reported in the first three participants showed an average microdystrophin expression of
“We are extremely pleased to present our initial clinical data from the INSPIRE DUCHENNE trial,” said Bo Cumbo, President and CEO, Solid Biosciences. “When starting this trial, we committed to comprehensively analyzing the effects of SGT-003. To that end, three different measurement methodologies showed what we believe to be potential best-in-class expression of our differentiated microdystrophin transgene. Significant reductions observed in all evaluated clinical biomarkers of muscle damage associated with Duchenne provide preliminary evidence of a beneficial effect in muscle integrity, including potential early signals of a positive cardiac benefit of SGT-003 in these young boys. In mid-2025, we plan to request a meeting with the FDA to discuss the potential for an accelerated approval regulatory pathway for SGT-003.”
SGT-003 was well-tolerated in the first six participants dosed as of the data cutoff date of February 11, 2025. As of the cutoff date, all six participants have reached at least 20 days post SGT-003 treatment. Adverse events (AEs) observed after SGT-003 treatment were typical of those observed in AAV gene therapy, including nausea, vomiting, fever and transient declines in platelets in some participants. No serious adverse events (SAEs) or suspected unexpected serious adverse reactions (SUSARs) were observed, and there was no evidence of thrombotic microangiopathy (TMA), atypical hemolytic uremic syndrome (aHUS), or hemolysis. Importantly, none of the AEs that were observed required the use of additional immunomodulatory agents such as eculizumab, sirolimus or rituximab.
“The robust microdystrophin expression, improvements in markers of muscle integrity and health, and favorable safety profile observed in this cohort of participants as of the data cutoff date of February 11, 2025, are very promising,” said Craig McDonald, MD, Chair, Department of Physical Medicine & Rehabilitation at UC Davis Health and investigator in the INSPIRE DUCHENNE trial. “In the landscape of genetic therapies for Duchenne, individual microdystrophin constructs likely have unique efficacy and safety profiles. I am very encouraged by the initial results reported today and look forward to seeing additional data and longer-term functional data that I believe will further inform our understanding of the role that the nNOS binding domain, which is unique to SGT-003, may play in improving clinical outcomes.”
“While loss of normal dystrophin is the defining molecular hallmark of Duchenne, there is growing understanding within the community that the success of microdystrophin gene therapy extends beyond expression, and will also depend on signals of restoration and preservation of muscle health, which were observed in these early clinical data,” said Gabriel Brooks, MD, Chief Medical Officer at Solid. “We are highly encouraged by the safety and tolerability profile observed, which has been consistent with AAV-based gene therapies. Additionally, though the trial was geared to follow cardiac measures for safety, we were gratified to observe early signs of cardiac benefit, including a decline in hs-troponin I levels in the participant with elevated levels at baseline, and improvements in cardiac function by echocardiography at day 180 in two participants with borderline low ejection fraction.”
INSPIRE DUCHENNE Trial Design
The INSPIRE DUCHENNE trial is a Phase 1/2 first in human, open-label, single-dose, multicenter trial designed to evaluate the safety, tolerability and efficacy of SGT-003 in pediatric patients with Duchenne at a dose of 1E14vg/kg. SGT-003 is administered as a one-time intravenous infusion. As of the data cutoff date of February 11, 2025, a total of six participants have been dosed in the INSPIRE DUCHENNE trial. Enrollment in the INSPIRE DUCHENNE trial is ongoing, with at least 10 total participants anticipated to be dosed by early in the second quarter of 2025 and approximately 20 total participants anticipated to be dosed by the fourth quarter of 2025.
INSPIRE DUCHENNE currently has a total of six active clinical sites in the United States and Canada and approved clinical trial applications (CTAs) in the United Kingdom and Italy. Solid expects to activate additional trial sites by the end of 2025.
90-Day Initial Data
The 90-day data reported today as of the data cutoff date of February 11, 2025, includes: microdystrophin expression, measures of restoration and activation of key elements of the dystrophin-associated protein complex, key muscle integrity biomarker evaluation, in each case, from the first three participants dosed in the INSPIRE DUCHENNE trial, and interim safety findings from the first six participants dosed in the INSPIRE DUCHENNE trial. The first three participants are two 5-year-old boys and one 7-year-old boy at the time of dosing. The second three participants are a 6-year-old boy and two 7-year-old boys at the time of dosing.
Microdystrophin Expression and Other Measures at Day 90:
| Mean (N=3) | Participant 1 | Participant 2 | Participant 3 | |
| Microdystrophin Expression % Normal (Western Blot) | ||||
| Microdystrophin Expression % Normal (Mass Spectrometry) | ||||
| % Dystrophin Positive Fibers (Immunofluorescence) | ||||
| Vector Copies/Nucleus | 18.7 | 19.8 | 28.6 | 7.6 |
| nNOS (neuronal nitric oxide synthase) % Positive Fibers | ||||
| Beta Sarcoglycan % Positive Fibers |
Muscle Integrity Biomarker Evaluation at Day 90 (N=3):
- Mean reductions observed in markers of muscle injury and stress:
- Serum creatine kinase (CK) (IU/L): -
57% - Serum aspartate aminotransferase (AST) (IU/L): -
45% - Serum alanine transaminase (ALT) (IU/L): -
54% - Serum lactate dehydrogenase (LDH) (IU/L): -
60%
- Serum creatine kinase (CK) (IU/L): -
- Mean reductions observed in markers of muscle breakdown and dystrophic regeneration:
- Serum titin (pmol/L): -
42% - Embryonic myosin heavy chain (eMHC) positive fibers: -
59%
- Serum titin (pmol/L): -
Measure of Potential Cardiac Benefit:
- At Day 180, mean cardiac function increased by
8% (N=2) from baseline as measured by left ventricular ejection fraction- The third participant had not reached Day 180 follow up as of the data cutoff date of February 11, 2025
- Reduction in serum cardiac hs-troponin I (hs-cTnI) of -
36% observed at Day 90 in one participant who entered the trial with elevated hs-cTnI levels- Two of the first three participants entered the study with normal baseline cTnI levels
- Two participants in total (N=6) had elevated troponin at baseline that reduced below initial baseline values post-dose
Safety Update for the First Six Participants Dosed:
- SGT-003 was well-tolerated
- No SAEs observed
- No SUSARs observed
- No hospitalizations reported
- No evidence of TMA or aHUS observed
- All treatment-related AEs resolved with no sequelae
- None of the AEs required the use of additional immunomodulatory agents such as eculizumab, sirolimus or rituximab
- No AEs of hepatic transaminitis observed, including no elevated gamma-glutamyl transferase (GGT) levels
- One adverse event of special interest (AESI) was observed
- Mild, transient hs-troponin I elevation observed (CTCAE Grade 1) that resolved without intervention
- No clinical evidence of myocarditis observed
- No EKG or echocardiographic changes observed
- Most common AEs observed:
- Nausea/vomiting
- Transient thrombocytopenia
- One CTCAE Grade 3 episode that resolved within days without intervention
- No evidence of hemolysis observed
- Infusion related hypersensitivity reaction
- One CTCAE Grade 3 episode of prolonged fever that resolved within days without intervention
- Fever
Conference Call
The Company will host a conference call today, February 18, 2025, at 8:00 AM ET to discuss the positive initial data from the Phase 1/2 INSPIRE DUCHENNE trial evaluating SGT-003. A live and archived webcast of the call will be available on Solid’s website at www.solidbio.com under the “Events” tab in the Investor Relations section, or by clicking here.
Participants may also access the live call by dialing 877-407-2991 (toll-free) or 201-389-0925 (international).
About Duchenne
Duchenne is a genetic muscle-wasting disease predominantly affecting boys, with symptoms usually appearing between three and five years of age. Duchenne is a progressive, irreversible, and ultimately fatal disease that affects approximately one in every 3,500 to 5,000 live male births and has an estimated prevalence of 5,000 to 15,000 cases in the United States alone.
About SGT-003
SGT-003 is an investigational gene therapy containing a differentiated microdystrophin construct and a proprietary, next-generation capsid, AAV-SLB101, which was rationally designed to target integrin receptors, and has shown enhanced cardiac and skeletal muscle transduction with decreased liver targeting in nonclinical studies. SGT-003’s microdystrophin construct uniquely includes the R16/17 domains, which localize nNOS to the muscle. Nonclinical studies have shown that nNOS can improve blood flow to the muscle thereby reducing muscle breakdown from ischemia and muscle fatigue. Together, these design features suggest that SGT-003 could be a potential best-in-class investigational gene therapy for the treatment of Duchenne.
About INSPIRE DUCHENNE
INSPIRE DUCHENNE is a first-in-human, open-label, single-dose, multicenter Phase 1/2 clinical trial to evaluate the safety, tolerability and efficacy of SGT-003 in pediatric participants with a genetically confirmed Duchenne diagnosis with a documented dystrophin gene mutation. INSPIRE DUCHENNE is a multinational trial designed to enroll participants in the United States, Canada, the United Kingdom and Italy.
About Solid Biosciences
Solid Biosciences is a precision genetic medicine company focused on advancing a portfolio of gene therapy candidates targeting rare neuromuscular and cardiac diseases, including Duchenne muscular dystrophy (Duchenne), Friedreich’s ataxia (FA), catecholaminergic polymorphic ventricular tachycardia (CPVT), TNNT2-mediated dilated cardiomyopathy, BAG3-mediated dilated cardiomyopathy, and additional fatal, genetic cardiac diseases. The Company is also focused on developing innovative libraries of genetic regulators and other enabling technologies with promising potential to significantly impact gene therapy delivery cross-industry. Solid is advancing its diverse pipeline and delivery platform in the pursuit of uniting experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted by Duchenne, Solid’s mission is to improve the daily lives of patients living with devastating rare diseases. For more information, please visit www.solidbio.com.
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding future expectations, plans and prospects for the Company; the ability to successfully achieve and execute on the Company’s goals, priorities and achieve key clinical milestones; the anticipated benefits of SGT-003; the Company’s SGT-003 clinical program, including planned enrollment and site activations in the INSPIRE DUCHENNE trial, planned regulatory interactions and the potential accelerated approval pathway; and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” “working” and similar expressions. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the Company’s ability to advance SGT-003, SGT-212, SGT-501, SGT-601, SGT-401 and other preclinical programs and capsid libraries on the timelines expected or at all; obtain and maintain necessary approvals and designations from the FDA and other regulatory authorities; replicate in clinical trials positive results found in preclinical studies and early-stage clinical trials of the Company’s product candidates; replicate preliminary or interim data from early-stage clinicals trials in the final data of such trials; obtain, maintain or protect intellectual property rights related to its product candidates; compete successfully with other companies that are seeking to develop Duchenne, Friedreich’s ataxia and other neuromuscular and cardiac treatments and gene therapies; manage expenses; and raise the substantial additional capital needed, on the timeline necessary, to continue development of SGT-003, SGT-212, SGT-501, SGT-601, SGT-401 and other candidates, achieve its other business objectives and continue as a going concern. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties and other important factors, in the Company’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date hereof and should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.
Solid Biosciences Investor Contact:
Nicole Anderson
Director, Investor Relations and Corporate Communications
Solid Biosciences Inc.
investors@solidbio.com
Media Contact:
Glenn Silver
FINN Partners
glenn.silver@finnpartners.com
This press release was published by a CLEAR® Verified individual.
FAQ
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