Deramiocel PDUFA Nears as Modest Phase 3 Benefit Faces No Precedent

Deramiocel BLA Under FDA Review with November PDUFA Date

Capricor Therapeutics announced its third-quarter 2026 financial results and provided a corporate update, primarily focusing on the regulatory progress of Deramiocel for Duchenne muscular dystrophy (DMD). The Biologics License Application (BLA) for Deramiocel is under FDA review, with a PDUFA target action date of November 22, 2026. A major amendment to the BLA included two-year open-label extension (OLE) data from the HOPE-3 trial, demonstrating a 76% slower upper limb decline in patients who switched from placebo to Deramiocel. The company also highlighted positive cardiac results from HOPE-3, which received an American Heart Association award, and the publication of HOPE-3 results in The Lancet. Capricor reported approximately $198.5 million in cash and equivalents as of September 30, 2026, and a net loss of $42.7 million for the quarter.

• Capricor's Biologics License Application (BLA) for Deramiocel in Duchenne muscular dystrophy (DMD) is currently under FDA review, with a PDUFA target action date set for November 22, 2026. The company submitted a major amendment to the BLA in August, incorporating two-year open-label extension (OLE) data from the Phase 3 HOPE-3 trial and proposing a refined indication targeting upper limb impairment in DMD patients over nine years old.
• Two-year open-label extension data from the HOPE-3 trial, presented at the 31st Annual World Muscle Society Congress, showed a substantial benefit for Deramiocel. Patients who transitioned from placebo to Deramiocel experienced a 76% slower decline in upper limb function, as measured by the Performance of the Upper Limb (PUL 2.0) scale, compared to their year on placebo, supporting the durability of the treatment effect.
• The HOPE-3 trial also yielded positive cardiac results, with data presented by Dr. Jonathan Soslow showing slower progression of myocardial fibrosis and improved left ventricular ejection fraction with Deramiocel. These cardiac findings earned an American Heart Association Outstanding Research Award. Furthermore, the comprehensive HOPE-3 results, including statistically significant slowing of upper limb disease progression, were published in The Lancet in July.
• As of September 30, 2026, Capricor Therapeutics maintained a strong financial position with approximately $198.5 million in cash, cash equivalents, restricted cash, and marketable securities. The company is actively advancing its manufacturing capabilities at its San Diego GMP facility and undertaking extensive launch preparations across distribution, patient support, market access, and medical affairs, anticipating potential approval.

Deramiocel's BLA: Addressing Critical Unmet Needs in DMD

Current treatment approaches for Duchenne muscular dystrophy offer limited long-term benefits while facing persistent safety, durability and eligibility constraints. AAV-based gene therapies show modest functional improvement with important immune risks, and exon-skipping and corticosteroid strategies are restricted by narrow applicability and significant morbidities.

• Unconfirmed durability and modest efficacy of AAV micro-dystrophin therapy: Delandistrogene moxeparvovec improved North Star Ambulatory Assessment (NSAA) scores by +3.08 points at 1 year (95% CI 1.85 to 4.32), with greater effects in 4-5 year-olds (+4.06) than in 6-7 year-olds (+1.01), yet long-term efficacy, durability, and safety remain unconfirmed and larger trials with longer follow-up are needed to clarify long-term efficacy and optimise risk-benefit profiles.

• Immune-mediated and serious systemic toxicities: Immune-mediated toxicities including myositis, myocarditis, and liver injury present significant clinical challenges, with immunogenicity against AAV capsids and transgene products; fordadistrogene movaparvovec was associated with immune-mediated serious adverse events, including thrombotic microangiopathy cases and patient deaths due to acute liver failure, ultimately leading to program discontinuation, while two myocarditis cases were reported within 4 days after delandistrogene moxeparvovec infusion.

• Vector, targeting and access limitations: Obstacles include the need for high viral titres, efficient muscle targeting and avoidance of immune response to vector and transgene, vector size limitations requiring dual/triple AAV systems or non-viral platforms, improving muscle tropism through capsid and promoter engineering, expanding eligibility through desensitization protocols, and difficult economic and logistical challenges for healthcare systems.

• Restricted applicability of exon-skipping antisense oligonucleotides: Eteplirsen is applicable to approximately 13% of DMD patients, and the four FDA-approved ASO therapies - eteplirsen, golodirsen, viltolarsen, and casimersen - face limited patient eligibility, discrepancies between preclinical efficacy and clinical outcomes, and accelerated approval based on limited clinical data with confirmatory trials to verify clinical efficacy actively underway.

• Corticosteroid morbidities and regimen uncertainty: Chronic corticosteroid treatment causes significant morbidities including excessive weight gain, behavioural abnormalities, cushingoid appearance, excessive hair growth, stunting of growth, asymptomatic spine compression deformities in 76% and long bone fractures in 30% in long-term daily glucocorticoid therapy, with questions remaining over optimal dosing, longer-term balance of benefits versus harms, and choice of corticosteroid or regimen.

HOPE-3 Data Supporting Deramiocel's Efficacy in DMD

Recent Duchenne muscular dystrophy trials span exon-skipping antisense oligonucleotides and AAV-based gene therapy. The studies below summarize design, intervention dosing, and reported safety and efficacy outcomes in ambulatory and young pediatric populations.

• Phase 2 randomized clinical trial (NCT02740972) of viltolarsen for exon 53 skipping: Participants aged 4 to 9 years with DMD amenable to exon 53 skipping received 40 mg/kg (low dose) or 80 mg/kg (high dose) of viltolarsen administered by weekly intravenous infusion, with a 4-week randomized period followed by a 20-week open-label treatment period. After 20 to 24 weeks, drug-induced dystrophin production by Western blot was 40 mg/kg per week: mean [range] 5.7% [3.2-10.3] of normal and 80 mg/kg per week: mean [range] 5.9% [1.1-14.4] of normal. Viltolarsen was well tolerated; no treatment-emergent adverse events required dose reduction, interruption, or discontinuation, and no serious adverse events or deaths occurred. Compared with 65 age-matched and treatment-matched natural history controls, all 16 participants showed improvements at week 25 in time to stand from supine (viltolarsen: -0.19 s; control: 0.66 s), time to run/walk 10 m (viltolarsen: 0.23 m/s; control: -0.04 m/s), and 6-minute walk test (viltolarsen: 28.9 m; control: -65.3 m).

• Open-label, multicenter, dose-escalation study (NCT03218995) of eteplirsen in boys aged 6-48 months amenable to exon 51 skipping: Cohort 1 aged 24-48 months (n = 9) and Cohort 2 aged 6 to < 24 months (n = 6) received ascending doses (2, 4, 10, 20, 30 mg/kg) of once-weekly eteplirsen intravenously over 10 weeks, continuing at 30 mg/kg up to 96 weeks. All 15 participants completed the study. Eteplirsen was well tolerated with no treatment-related discontinuations, deaths or evidence of kidney toxicity. Most treatment-emergent adverse events were mild; most common were pyrexia, cough, nasopharyngitis, vomiting, and diarrhea. Eteplirsen pharmacokinetics were consistent between both cohorts and with previous clinical experience in boys with DMD > 4 years of age.

• Phase 3 EMBARK trial (NCT05096221) of delandistrogene moxeparvovec: Phase 3, two-part, crossover, randomized, placebo-controlled trial assessing single intravenous dose 1.33 × 10 vector genomes/kg in ambulatory male patients with DMD aged 4 to < 8 years (N = 125). At 2 years, EMBARK patients showed statistically significant benefit versus a matched propensity score-weighted external control in functional outcomes prognostic for delaying loss of ambulation (NSAA, Time to Rise, 10-m Walk/Run). Delandistrogene moxeparvovec micro-dystrophin expression and sarcolemmal localization were maintained over 64 weeks. No new safety signals were observed between week 52 and week 104. Between baseline and week 104, there were no treatment-related deaths, study discontinuations due to adverse events, or clinically significant complement-mediated adverse events.

Positioning Deramiocel in the DMD Treatment Landscape

Delandistrogene moxeparvovec, a recombinant adeno-associated virus rhesus isolate serotype 74 vector-based gene therapy that addresses the absence of functional dystrophin in Duchenne muscular dystrophy (DMD), has moved from investigational testing to regulatory authorization. Developed by Sarepta Therapeutics, it is the first gene therapy to be approved (in June 2023 under the Accelerated Approval pathway) for the treatment of DMD in the USA, where it is indicated for ambulatory paediatric patients aged 4 through 5 years with DMD and a confirmed mutation in the DMD gene, at a recommended dose of 1.33 × 10 vector genomes per kg of body weight administered as a single intravenous infusion. The phase 3 EMBARK study (NCT05096221) randomized ambulatory males with DMD, ≥4 years to <8 years of age, to single-administration intravenous delandistrogene moxeparvovec (1.33 × 10 vector genomes per kilogram; n = 63) or placebo (n = 62). At week 52, the primary endpoint, change from baseline in North Star Ambulatory Assessment (NSAA) score, was not met (least squares mean 2.57 (delandistrogene moxeparvovec) versus 1.92 (placebo) points; between-group difference, 0.65; 95% confidence interval (CI), -0.45, 1.74; P = 0.2441), while mean micro-dystrophin expression at week 12 was 34.29% (treated) versus 0.00% (placebo).

Longer follow-up and additional trials have contextualized functional outcomes versus external controls. At 2 years, EMBARK patients showed statistically significant benefit versus a matched propensity score-weighted external control (EC) cohort in functional outcomes prognostic for delaying loss of ambulation (NSAA, Time to Rise, 10-m Walk/Run), demonstrating sustained stabilization or slowing of disease progression, with micro-dystrophin expression and sarcolemmal localization maintained over 64 weeks. In ENDEAVOR (SRP-9001-103; NCT04626674) cohort 1 (N = 20), change from baseline to week 12 in delandistrogene moxeparvovec micro-dystrophin by western blot was mean (SD) 54.2% (42.6); p < 0.0001, with 1-year NSAA mean (SD) change +4.0 (3.5) and +3.2 (0.6) points versus propensity score-weighted external natural history control; p < 0.0001. In Study 101 (NCT03375164), four patients (mean age, 5.1 years) increased mean NSAA total score from 20.5 to 27.5, baseline to year 4, with mean change of +7.0 (2.9) and least-squares mean [standard error] = 9.4 [3.4]; P = .0125 versus EC, and at 5 years mean change +7.5 (2.4) versus -3.9 (2.9) (least-squares mean between-group difference [standard error]: 9.8 [3.5], p = 0.0127), with all treated patients (mean age, 10.2 years) remaining ambulant. By contrast, fordadistrogene movaparvovec (Pfizer) showed encouraging biomarker results but was associated with immune-mediated serious adverse events, including thrombotic microangiopathy cases and patient deaths due to acute liver failure, ultimately leading to program discontinuation, while GNT0004, SGT-003, and RGX-202 are currently in early- to mid-phase evaluation.

The corticosteroid paradigm has also evolved with vamorolone, a dissociative corticosteroid approved by the US Food and Drug Administration in 2023 for treating DMD. In a randomized, double-blind, placebo- and prednisone-controlled 24-week trial in boys 4 to younger than 7 years of age, the trial met the primary end point for change from baseline to week 24 time to stand velocity for vamorolone, 6 mg/kg per day (least-squares mean [SE] velocity, 0.05 [0.01] m/s vs placebo -0.01 [0.01] m/s; 95% CI, 0.02-0.10; P = .002), with height percentile change prednisone, -1.88 [8.81] percentile vs vamorolone, 6 mg/kg per day, +3.86 [6.16] percentile; P = .02, and bone turnover markers declined with prednisone but not with vamorolone. Improvements with 6 mg/kg/d at 24 weeks were maintained to 48 weeks, with reversal of prednisone-induced decline in bone turnover biomarkers and significant improvement in linear growth after crossover from prednisone to vamorolone. Safety management of gene therapy remains central, with 674 adverse events recorded with delandistrogene moxeparvovec and 514 with placebo in EMBARK, 7 patients (11.1%) experiencing 10 treatment-related serious adverse events, no deaths, discontinuations or clinically significant complement-mediated adverse events, and acute liver injury recognized with progression to acute liver failure in two nonambulatory patients (ages 15 and 16 years) representing the only known instances following delandistrogene moxeparvovec to date.