HOPE-3 Meets Upper-Limb Primary but Cardiac Claim Lacks Numbers Ahead of BLA

Capricor's Deramiocel Cardiac Results Win AHA Outstanding Research Award

Capricor Therapeutics announced that cardiac results from its HOPE-3 Phase 3 trial of Deramiocel in Duchenne muscular dystrophy (DMD) received the Outstanding Research Award in Pediatric Cardiology at the American Heart Association (AHA) Scientific Sessions 2026. The presentation, held on November 7 in Chicago, included new cardiac MRI data on myocardial fibrosis (LGE) and a comparison with natural history data. The trial, which randomized 106 patients, met its primary endpoint of upper limb function. The key secondary endpoint was change in left ventricular ejection fraction (LVEF). Deramiocel showed improvements in LVEF, particularly in patients with cardiomyopathy, and slower progression of heart scarring (LGE) compared to placebo and natural history. The Biologics License Application for Deramiocel is under FDA review with a PDUFA target action date of November 22, 2026.

• Capricor's Deramiocel cardiac results from the HOPE-3 Phase 3 trial were honored with the Outstanding Research Award in Pediatric Cardiology at the American Heart Association (AHA) Scientific Sessions 2026. The presentation, led by Dr. Jonathan Soslow, included novel cardiac MRI data on myocardial fibrosis (LGE) and a comparison against a natural history dataset, highlighting the significance of these findings in the cardiology community.
• In the HOPE-3 trial, Deramiocel demonstrated pronounced improvements in ventricular function, particularly within the prespecified cardiomyopathy subgroup, where LVEF increased by +2.8 percentage points (p=0.02 vs. placebo; p=0.01 vs. natural history). This finding is critical as cardiomyopathy is the leading cause of death in DMD, and these results suggest a potential for stabilization of heart function.
• Beyond functional improvements, Deramiocel treatment also led to a slower progression of heart scarring, with 3.0 fewer new scarred heart segments (p=0.02 vs. placebo; p=0.01 vs. natural history). These robust cardiac findings, previously published in The Lancet, support the ongoing Biologics License Application (BLA) for Deramiocel, which is currently under FDA review with a PDUFA target action date of November 22, 2026, addressing a significant unmet need in DMD.

Addressing the Urgent Need in DMD Cardiomyopathy Treatment

Current treatment approaches for Duchenne muscular dystrophy face persistent limitations across gene therapy delivery, durability of benefit, and systemic toxicity. Long-term glucocorticoids (GC) remain the backbone of treatment for the foreseeable future, yet cardiac dysfunction remains a frequent manifestation and common cause of death with no targeted therapy.

• Preexisting AAV immunity attenuates vascular gene transfer. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). Immunosuppression did not affect transgene expression in this isolated limb perfusion model.

• Innate and adaptive immune responses require modulation and carry safety risks. Both innate and adaptive immune responses have been observed in human trials to the AAV vector and the transgene product. Strategies tested include no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil), a brief course of immunosuppression with a combination of anti-thymocyte globulin (ATG), cyclosporine (CSP), and mycophenolate mofetil (MMF), and daily prednisolone, 1 mg/kg, started 1 day before gene delivery (30-day taper after infusion). Enthusiasm has been hampered by dose-dependent immunologic reactions such as hepatotoxicity, acquired hemolytic uremic syndrome and myocarditis.

• Corticosteroid efficacy is short-term with uncertain long-term benefit. Moderate quality evidence indicates corticosteroid therapy (0.75 mg/kg/day prednisone or prednisolone) improved muscle strength and function versus placebo over six months and strength up to two years, with improvements in time taken to rise from the floor (Gowers' time), timed walk, four-stair climbing time, ability to lift weights, leg function grade, and forced vital capacity. There is no evidence other than from non-randomised trials to establish the effect of corticosteroids on prolongation of walking, and long-term benefits and hazards cannot be evaluated from published RCTs.

• Corticosteroid and GC toxicity limits sustained use. Excessive weight gain, behavioural abnormalities, cushingoid appearance, and excessive hair growth were all more common with corticosteroids than placebo. Serious complications of GC therapy include unexpected mortality due to fat embolism syndrome following bone injury and also unrecognized adrenal suppression, early loss of ambulation linked to excess weight and/or fragility fracture, adverse cardiometabolic effects of GC, and profound growth and pubertal delay/hypogonadism. Data are insufficient to assess the risk of fractures or cataracts for any comparison.

• Cardiac disease lacks targeted treatment and trial endpoints are challenging. Early diastolic dysfunction and focal fibrosis proceed to dilated cardiomyopathy (DCM), complicated by heart failure and arrhythmia in most patients. Since the specific mechanisms resulting in heart failure are poorly understood, current treatments are not targeted, but rely on approaches that are considered standard for DCM including angiotensin-converting enzyme (ACE) inhibitors and β-adrenoceptor antagonists. Appropriate clinical endpoints are the prolongation of the ability to stand from the floor, climb stairs, and walk, not an increase in muscle strength or function, with time frames for detection of new dystrophin within months versus years to demonstrate slowing of disease progression.

HOPE-3: Unpacking Deramiocel's Cardiac Trial Design and Results

Recent Duchenne muscular dystrophy trials evaluate dissociative steroids, NF-κB inhibition, exon skipping, micro-dystrophin gene transfer and cell therapies across ambulant and non-ambulant populations. Designs include randomized double-blind placebo-controlled phase 2 and phase 3 studies with motor function primary endpoints and safety follow-up.

Deramiocel's Potential Impact on the DMD Treatment Landscape

AAV-based mini- and micro-dystrophin gene therapies have entered large-scale human testing, with delandistrogene moxeparvovec as a recombinant adeno-associated virus rhesus isolate serotype 74 vector-based gene therapy that addresses the absence of functional dystrophin. In the phase 3 EMBARK trial (NCT05096221), 125 ambulatory male patients aged 4 to <8 years were randomized to single-administration intravenous delandistrogene moxeparvovec or placebo. At week 52, change from baseline in North Star Ambulatory Assessment [NSAA] total score was 2.57 (delandistrogene moxeparvovec) versus 1.92 (placebo) points, with a between-group difference of 0.65 (95% confidence interval [CI], -0.45, 1.74; P = 0.2441). Mean micro-dystrophin expression at week 12 was 34.29% (treated) versus 0.00% (placebo), with between-group differences at week 52 for Time to Rise (-0.64 (-1.06, -0.23)), 10-meter Walk/Run (-0.42 (-0.71, -0.13)), time to ascend 4 steps (-0.36 (-0.71, -0.01)), and 100-meter Walk/Run (-3.29 (-8.28, 1.70)). In total, 674 adverse events were recorded with delandistrogene moxeparvovec and 514 with placebo, with 7 patients (11.1%) experiencing 10 treatment-related serious adverse events and no deaths, discontinuations or clinically significant complement-mediated adverse events. Two-year follow-up versus a matched propensity score-weighted external control showed statistically significant benefit in NSAA, Time to Rise and 10-m Walk/Run, with micro-dystrophin expression and sarcolemmal localization maintained over 64 weeks and no new safety signals between week 52 and week 104.

Vamorolone, a dissociative corticosteroid approved by the US Food and Drug Administration in 2023, has been evaluated in corticosteroid-naive and corticosteroid-treated boys. Study VBP15-006 (NCT05185622) was a 12-week, phase II, open-label, multiple-dose study of 2 or 6 mg/kg/d oral vamorolone. In 20 boys aged 2-<4 years (mean age [SD] 3.4 [0.39] years), treatment-emergent adverse events were mostly mild, with no deaths, serious treatment-emergent adverse events, or events leading to discontinuation, with gastrointestinal disorders and infections/infestations most reported. Vamorolone displayed a dose-dependent pharmacokinetic profile with rapid absorption and no accumulation, with morning serum cortisol reductions in all patients, stable growth trajectories, and dose-dependent improvements in motor function measured by Bayley-III gross motor scaled score. In 34 participants aged 7- to <18 years (12 corticosteroid-untreated, 22 corticosteroid-treated), all completed VBP15-006, with stable linear growth in untreated participants and catch-up growth in treated participants, dose-dependent adrenal suppression, and no relevant efficacy changes at either dose. In a randomized, double-blind, placebo-controlled and prednisone-controlled trial in 121 participants aged 4 years to younger than 7 years, vamorolone 6 mg/kg/d showed maintenance of improvement for all motor outcomes to week 48, with time to stand from supine velocity week 24 least squares mean [SE] 0.052 [0.0130] rises/s versus week 48 0.0446 [0.0138], with significant improvement in linear growth after crossover from prednisone and rapid reversal of prednisone-induced decline in bone turnover biomarkers.

Mutation-specific exon-skipping and readthrough approaches have reported long-term functional data alongside corticosteroid standard of care. In Study 201/202, 12 eteplirsen-treated patients showed a difference in change from baseline in 6-minute walk test of 132 m (95%CI (29, 235), p = 0.015) at Year 3 and 159 m (95%CI (66, 253), p = 0.002) at Year 4 versus matched controls from Italian Telethon and Leuven registries, with 10/12 versus 3/11 still ambulant at Year 4 (p = 0.020). Golodirsen 30 mg/kg in exon 53 skip-amenable patients increased dystrophin protein (16.0-fold; P < 0.001) and exon skipping (28.9-fold; P < 0.001), with 3-year 6-minute walk test change of -99.0 m versus -181.4 m for external controls (P = 0.067) and loss of ambulation in 9% versus 26% (P = 0.21). Viltolarsen 40 mg/kg per week and 80 mg/kg per week produced mean 5.7% [3.2-10.3] and 5.9% [1.1-14.4] of normal dystrophin, with improvements versus 65 natural history controls in time to stand from supine (-0.19 s versus 0.66 s), time to run/walk 10 m (0.23 m/s versus -0.04 m/s), and 6-minute walk test (28.9 m versus -65.3 m). Ataluren follow-up showed median exposure of 2312 days and loss of ambulation at median age of 13.2 years, while pamrevlumab 35-mg/kg intravenous infusions every 2 weeks for 2 years in 21 non-ambulatory patients aged ≥12 years showed annual change in percent predicted forced vital capacity of -4.2 (0.7) (95% CI -5.5, -2.8). Fordadistrogene movaparvovec showed smaller effects than delandistrogene moxeparvovec and was associated with immune-mediated serious adverse events, including thrombotic microangiopathy cases and patient deaths due to acute liver failure, leading to program discontinuation.