A Randomized, Double-Blind, Dose Finding and Comparison Study of the Safety and Efficacy of High Doses of Eteplirsen, Preceded by an Open-label Dose Escalation, in Patients With Duchenne Muscular Dystrophy With Deletion Mutations Amenable to Exon 51 Skipping

Part 1 (dose escalation) will evaluate the safety and tolerability of 2 doses (100 milligrams/kilogram [mg/kg] and 200 mg/kg) of eteplirsen in approximately 10 participants with DMD; Part 2 (dose finding and dose comparison) will evaluate the efficacy and safety of the high doses (100 mg/kg and 200 mg/kg) of eteplirsen compared with that of the 30 mg/kg dose of eteplirsen, in approximately 144 participants with genetically confirmed deletion mutations amenable to treatment by skipping exon 51.

Start Date13 Jul 2020

Sponsor / Collaborator

Sarepta Therapeutics, Inc.

NCT04179409

/ CompletedPhase 2IIT

A 48-Week, Open Label, Study to Evaluate the Efficacy and Safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 in Subjects With DuchenneMuscular Dystrophy Carrying Eligible DMD Duplications.

This is an 48-week open-label study to determine the efficacy and safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 for the treatment of boys with duchenne muscular dystrophy who have a single exon duplication of either exon 45, 51 or 53, respectively. There will be weekly infusions and two muscle biopsies at baseline and at month 12.

Start Date18 Feb 2020

Sponsor / Collaborator

Nationwide Children's Hospital

[+1]

NCT03985878

/ TerminatedPhase 2

An Open-Label Safety, Tolerability, and Efficacy Study of Eteplirsen in Patients With Duchenne Muscular Dystrophy Who Have Completed Study 4658-102

The purpose of this extension study is to evaluate the ongoing safety and tolerability of additional treatment with eteplirsen administered once weekly by intravenous (IV) infusion in male participants with DMD who have successfully completed the 96-week eteplirsen Study 4658-102.

Start Date26 Jun 2019

Sponsor / Collaborator

Sarepta Therapeutics, Inc.

100 Clinical Results associated with Eteplirsen

100 Translational Medicine associated with Eteplirsen

100 Patents (Medical) associated with Eteplirsen

137

Literatures (Medical) associated with Eteplirsen

01 May 2025·CPT-Pharmacometrics & Systems Pharmacology

A Population Pharmacokinetic Model to Inform Extension of the Eteplirsen Dosing Regimen Across the Broad DMD Population

Article

Author: Yocum, Nicole ; Orogun, Larry ; East, Lilly ; Rodino‐Klapac, Louise R. ; Patel, Yogesh

ABSTRACT:

Duchenne muscular dystrophy (DMD) is characterized by progressive, irreversible muscle damage that usually leads to premature death from cardiac or respiratory failure. Eteplirsen is a phosphorodiamidate morpholino oligomer and the first antisense oligonucleotide (ASO) approved for the treatment of patients with exon 51 skip‐amenable DMD. This analysis presents the first population pharmacokinetics (PK) modeling and simulation performed for the ASO drug class in DMD. Study objectives were to characterize the population PK of eteplirsen in patients with DMD across a broad age range and to identify the impact of covariates on eteplirsen exposure to guide clinical dosing. Plasma concentration data were pooled from six clinical studies of male patients with DMD across the age range of 6 months to 4 years (1 study) and 4–16 years (5 studies). Doses ranged from 0.5 to 50 mg/kg/week across different studies. A three‐compartment model with a linear elimination described the eteplirsen plasma concentration data well. Body weight effect on all PK parameters and eGFR, and age (≤ 4 years vs. > 4 years) effect on systemic clearance were key determinants of variability in the final model. Simulations showed similar exposures for eteplirsen (30 mg/kg intravenously once weekly) across different age groups (0.5 to < 2, 2 to < 4, 4 to < 7, and 7 to ≤ 16 years). These findings support the existing eteplirsen dosing paradigm of uniform weight‐based dosing at 30 mg/kg/week across the broad age range of the target DMD population (6 months to adolescence).

01 Apr 2025·MOLECULAR THERAPY

Clinical applications of exon-skipping antisense oligonucleotides in neuromuscular diseases

Review

Author: Muntoni, Francesco ; Zhou, Haiyan ; Aguti, Sara ; Torres-Masjoan, Laia

Four exon-skipping antisense oligonucleotides (ASOs) have been approved by the US Food and Drug Administration (FDA) for the treatment of Duchenne muscular dystrophy (DMD), including eteplirsen, golodirsen, viltolarsen, and casimersen. Current data from long-term real-world usage of these ASOs suggests a broad safety profile and a delay in muscle deterioration. Nevertheless, the exon-skipping efficacy and dystrophin protein production of these ASOs are limited, suggesting the need for more efficient ASOs. Over the past decade, many studies have focused on improving ASO efficacy by incorporating novel chemical modifications or bioconjugations of a variety of moieties including peptides or antibodies to increase their cellular uptake by muscle cells, their endosomal escape, and their nuclear import to boost therapeutic efficacy. Many of these newly developed exon-skipping ASOs have been studied in clinical trials in DMD patients, and early findings suggest clear improvements in molecular efficacy compared to the earlier version of ASOs, although the safety track record may not be the same as the first-generation compounds. Here, we summarize the recent preclinical and clinical developments of ASOs and discuss the future challenges of exon-skipping therapies for DMD and other neuromuscular diseases.

10 Jan 2025·Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics

[Antisense oligonucleotide as novel therapies for neurogenetic disorders].

Review

Author: Fan, Liyuan

Antisense oligonucleotide (ASO) was discovered several decades ago and initially used only as a research tool in the laboratory. In recent years, several ASO therapeutics have been developed for neurological disorders. Some of these therapeutics, including eteplirsen, golodirsen, viltolarsen, nusinersen and inotersen, have been approved by the Food and Drug Administration (FDA) and begun to draw the public's attention as an effective therapeutic approach. These novel therapeutics have shown great performance, while many similar therapeutics are under investigation and in clinical trials. This n-of-1 precision medicine may start a new chapter in the paradigm of therapeutics. Clinicians, clinical geneticists, and genetic counselors may know about this novel therapy, but very few may understand the background in details. During genetic counseling, they have the responsibility to convey the effectiveness, side effects and cost of such therapies to patients and their families. As these target therapies will require precise genetic diagnosis before treatment, healthcare professionals and genetic counselors play a vital role in relating the patients to the corresponding ASO drugs. This review has elaborated the mechanism of ASO therapies, including basic rationales, modifications, side effects and delivery routes. It also systemically summarized the FDA-approved ASO therapeutics and their applications for various neurological disorders, and discussed the limitations and challenges the real-world market may face and issues genetic counselor should take into consideration in the near future.

204

News (Medical) associated with Eteplirsen

14 May 2025

·www.globenewswire.com

Inozyme Pharma Reports First Quarter 2025 Financial Results and Provides Business Highlights

- Interim data from ENERGY 3 trial highlight INZ-701’s potential to modify disease course in ENPP1 Deficiency, with sustained phosphate increases and favorable safety and immunogenicity profile to date - - ENERGY 3 trial on track for topline data in first quarter of 2026; no patient dropouts, dose adjustments or discontinuations, and no new safety signals - - Petra Duda, M.D., Ph.D. appointed Chief Medical Officer - BOSTON, May 14, 2025 (GLOBE NEWSWIRE) -- Inozyme Pharma, Inc. (Nasdaq: INZY) (“the Company” or “Inozyme”), a clinical-stage biopharmaceutical company developing innovative therapeutics for rare diseases that affect bone health and blood vessel function, today reported financial results for the first quarter ended March 31, 2025, and provided business highlights. “We are extremely pleased with how the ENERGY 3 trial is progressing,” said Douglas A. Treco, Ph.D., CEO and Chairman of Inozyme Pharma. “The consistency we have observed across safety, immunogenicity, and increases in phosphate levels reinforces our conviction in INZ-701’s ability to address the underlying biology of ENPP1 Deficiency. With no dropouts or dose modifications to date, the emerging profile in pediatric patients is highly encouraging. As we move toward topline data in the first quarter of 2026, we believe INZ-701 is well positioned to become the first approved therapy for this serious and underserved disease.” ENERGY 3 Pivotal Trial Update: Positive Trends in Safety, Phosphate Levels, and Immunogenicity Support INZ-701’s Potential The ENERGY 3 trial evaluating INZ-701 in pediatric patients with ENPP1 Deficiency completed enrollment in January 2025. Dosing is expected to conclude in January 2026, with topline data anticipated in the first quarter of 2026. To date, there have been no patient discontinuations, dose adjustments, or dosing holidays due to safety or tolerability concerns. The Data Safety Monitoring Board (DSMB) has not identified any new safety signals. Preliminary Anti-Drug Antibody (ADA) Data from ENERGY 3 Trial The Company today announced preliminary anti-drug antibody (ADA) data from the ENERGY 3 trial, based on an evaluation conducted as part of ongoing safety monitoring. This analysis included 17 of the 19 patients in the INZ-701 treatment arm who had completed at least 13 weeks of dosing. Of these 17 patients, 15 had no detectable ADAs or low titer responses. The highest titer among these 15 patients was 1,280 - a level comparable to those previously observed in the Company’s adult trials (INZ701-101 and INZ701-201). These titer levels in adults had no effect on drug exposure or patient safety and typically declined over time with continued treatment. Two of the 17 patients exhibited higher-titer ADA responses (5,120 and 40,960) similar to levels observed in some infants. These infants had reduced drug exposure yet still showed potentially clinically beneficial transient increases in PPi. The median ADA titer at Week 13 was 80 across all 17 patients. At this time, ADAs have not been associated with any impact on patient tolerability or adverse events. The safety and immunogenicity profile observed to date in the ENERGY 3 trial is encouraging and consistent with what was observed in our prior Phase 1/2 trials in adults. Additional Immunogenicity Insights from ENERGY 1 Trial and Expanded Access Program Today, the Company also updated observations on ADAs from its ENERGY 1 clinical trial and Expanded Access Program (EAP). In INZ-701-treated infants who developed high-titer ADAs affecting exposure (n=3), titers stabilized or declined over time, following transition to twice-weekly dosing or a dose increase. These data suggest that extended treatment duration, dose concentration and/or increased dosing frequency may help mitigate immunogenicity, an observation that is well-documented across other enzyme replacement therapies (ERTs). Notably, one infant with high-titer ADAs carried the same homozygous mutation as an adult patient in our completed Phase 1/2 trial who had a low titer antibody response (range 40-160), suggesting that impactful ADA responses may be restricted to the youngest patients. Interim Biomarker Data from ENERGY 3 Support Potential for Skeletal Improvement Along with pyrophosphate (PPi) deficiency, low serum phosphate (hypophosphatemia) is the key driver of rickets and osteomalacia in patients with ENPP1 Deficiency. We believe that by demonstrating an ability to increase serum phosphate levels, INZ-701 can meaningfully reduce the clinical burden of skeletal abnormalities. Interim data from ENERGY 3 demonstrate that mean serum phosphate levels increased over time in the INZ-701 arm, while levels declined in the conventional therapy arm, despite ongoing active vitamin D3 and phosphate supplementation. At Week 13, mean serum phosphate levels increased from baseline by +8.2% in the INZ-701 arm (n=17), compared to a decrease of -0.04% in the conventional treatment arm (n=7). The separation in serum phosphate levels between arms increased over time. By Week 26, mean phosphate levels increased by +6.8% in the INZ-701 arm (n=11) and decreased -5.5% in the conventional treatment arm (n=6). Through Week 39, mean phosphate levels increased by +12.1% in the INZ-701 arm (n=4), versus a -9.0% decrease in the conventional treatment arm (n=2). Overall, 6 of 17 patients (35%) treated with INZ-701 achieved normal serum phosphate levels at least once, while no patients in the conventional treatment arm reached the normal range. % mean change of serum phosphate from baselineTreatment Week 13 (n)Week 26 (n)Week 39 (n)INZ-701 +8.2 (17)+6.8 (11)+12.1 (4)Conventional Tx -0.04 (7)-5.5 (6)-9.0 (2) INZ-701 increased serum phosphate in ENERGY 3 pivotal trial Normal serum phosphate levels for this group of patients ranged from 3.1 to 6.1 milligrams/deciliter (mg/dL), as indicated by the pink shaded area. The normal range of serum phosphate levels varies by age and sex, and ranges may vary by testing laboratory. Data: Mean ± SD; Conventional Tx: active vitamin D3 + phosphate The upward trajectory of serum phosphate levels towards normalization over time supports the potential of INZ-701 to address the underlying pathophysiology of ENPP1 Deficiency and improve long-term skeletal outcomes. “These emerging data on serum phosphate levels suggest that INZ-701 may have a meaningful impact on the severity of rickets and other skeletal complications in children with ENPP1 Deficiency,” said Thomas Carpenter, M.D., Professor of Pediatrics and Orthopaedics at Yale School of Medicine, who is not involved in the study. “The consistency of the safety profile and biomarker responses to date is encouraging and supports further clinical development.” Leadership Transition Petra Duda, M.D., Ph.D. Appointed Chief Medical Officer. The Company today announced the appointment of Petra Duda, M.D., Ph.D., as Chief Medical Officer, effective May 15, 2025. Dr. Duda will succeed Kurt Gunter, M.D., who will retire and transition to an advisory role. Dr. Duda brings more than two decades of global clinical development, medical affairs, and regulatory leadership, with deep expertise in rare and ultra-rare diseases. Prior to joining Inozyme in November 2024, Dr. Duda served as Global Development Lead at UCB, where she oversaw the Zilbrysq® (zilucoplan) program and led it through global approvals for generalized myasthenia gravis. She joined UCB through its acquisition of Ra Pharmaceuticals, where she directed clinical development for complement pathway inhibitors. Earlier in her career, she played pivotal roles in the advancement and approval of Exondys 51® for Duchenne Muscular Dystrophy at Sarepta Therapeutics, led neurology programs at Biogen Idec, and supported medical affairs and drug safety at Boehringer Ingelheim. She is board certified in Neurology and Pharmaceutical Medicine and holds both an M.D. and Ph.D. in molecular biology and biochemistry from the University of Bern. Dr. Treco added, “I’ve been fortunate to work with both Kurt and Petra in the past. Petra is a strategic and thoughtful leader with deep experience in rare diseases. We are fortunate to have her step into this role as we prepare for late-stage development milestones. Kurt provided extraordinary leadership at critical junctures in the Company’s evolution. We are grateful for his outstanding contributions, and we will continue to benefit from his guidance as an advisor to the Company.” Recent Clinical and Scientific Progress ICD-10 Codes Accepted for ENPP1 Deficiency; Effective October 2025. The Company announced that the U.S. Centers for Medicare & Medicaid Services (CMS) has accepted a new set of ICD-10 diagnosis codes to support the classification of disorders of pyrophosphate metabolism, including ENPP1 Deficiency. These include distinct codes for generalized arterial calcification of infancy (GACI), autosomal recessive hypophosphatemic rickets type 2 (ARHR2), and pseudoxanthoma elasticum (PXE). The codes are expected to be published in early September 2025 and go into effect in October 2025.Regulatory Progress in Japan for ENPP1 Deficiency. In the first quarter of 2025, the Company reached agreement with Japan’s Pharmaceuticals and Medical Devices Agenda (PMDA) on a regulatory filing strategy for INZ-701 in ENPP1 Deficiency. Notably, the PMDA has agreed to accept data generated from clinical trials conducted outside of Japan and will not require the inclusion of Japanese patients for filing. This agreement provides a clear path toward potential approval in Japan.JBMR Plus Publication Demonstrating Real-World Impact of ENPP1 Deficiency. In April 2025, the Company announced a publication in JBMR Plus titled, “Phenotypic characterization of ENPP1 deficiency: generalized arterial calcification of infancy and autosomal recessive hypophosphatemic rickets type 2”. The publication characterized the severity and progression of ENPP1 Deficiency based on data from the largest retrospective analysis of the disease.Positive Interim Data from the ENERGY 1 trial and Expanded Access Program. In January 2025, the Company reported positive interim data from its ENERGY 1 trial and Expanded Access Program (EAP) evaluating INZ-701 in infants and young children with ENPP1 Deficiency demonstrating improvements from baseline in multiple measures of disease. The data were subsequently presented at the CHOP Cardiology 2025 Annual Meeting in February 2025. Recent Scientific Presentations at ESPE/ESE 2025 Joint Congress Inozyme recently featured new clinical insights and hosted an educational symposium at the Joint Congress of the European Society for Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE), held in May 2025 in Copenhagen, Denmark. Highlights included: New Poster Presentation: Leanne Ward, M.D. presented “Quantitative evaluation of hypophosphatemic rickets due to ENPP1 Deficiency,” a multi-center, retrospective analysis of children and adults with autosomal hypophosphatemic rickets type 2 (ARHR2). The data demonstrated that children with ENPP1 Deficiency under current standard of care exhibit persistent FGF23-mediated hypophosphatemia, with serum phosphate levels declining sharply in early childhood. Additional findings included rickets with clinical overlap with X-linked hypophosphatemia (XLH), impaired growth, delayed bone age, and decreased bone strength. These findings underscore the significant unmet need in ARHR2 and reinforce the value of genetic testing for accurate diagnosis.Data on Heterozygous ENPP1 Deficiency: David Weber, M.D., MSCE, presented emerging clinical observations in individuals with a single ENPP1 variant, contributing to the growing recognition that some ENPP1 carriers may exhibit clinically significant disease.Inozyme-Sponsored Symposium: On Sunday, May 11, Dr. Lothar Seefried led a symposium titled “Hypophosphatemic Rickets: Practical Tips for Distinguishing ARHR2 from XLH.” The session offered clinical and molecular insights into the differences between XLH and ARHR2, with an emphasis on improving diagnostic accuracy and guiding appropriate treatment strategies. First Quarter 2025 Financial Results Cash Position and Financial Guidance. Cash, cash equivalents, and short-term investments were $84.8 million as of March 31, 2025. Based on its current plans, the Company anticipates its cash, cash equivalents, and short-term investments as of March 31, 2025, will enable the Company to fund cash flow requirements into the first quarter of 2026.Research and Development (R&D) Expenses. R&D expenses were $20.4 million for the quarter ended March 31, 2025, compared to $19.1 million for the prior-year period. R&D increased $1.3 million primarily due to an increase in INZ-701-related research and development expense composed of a $2.2 million increase in CMC, offset by a $0.9 million decrease in clinical development and consulting costs. General Administrative (G&A) Expenses. G&A expenses were $5.4 million for the quarter ended March 31, 2025, compared to $5.2 million for the prior-year period. Restructuring charges. Restructuring charges were $1.9 million for the quarter ended March 31, 2025 with no comparable charge in the prior period. This increase relates to the Company’s reprioritization to focus resources on its ENPP1 Deficiency program, which resulted in a reduction of the Company’s workforce by approximately 25% across all areas of the Company. These charges relate to severance, benefits, and other costs. Net Loss. Net loss was $28.0 million, or $0.44 loss per share, for the quarter ended March 31, 2025, compared to $23.3 million or $0.38 loss per share for the prior-year period. About the ENERGY 3 Trial The ENERGY 3 trial is a pivotal, multicenter, randomized (2:1) controlled, open-label pivotal clinical trial designed to evaluate the efficacy and safety of INZ-701 in children aged 1 to under 13 years with ENPP1 Deficiency. Based on recommendations from the U.S. Food and Drug Administration (FDA), the trial’s primary endpoint, plasma pyrophosphate (PPi), should be supported by consistent trends in clinical endpoints such as radiographic impression of change (RGI-C), a measure for progression or improvement of rickets. In alignment with the European Medicines Agency (EMA), plasma PPi and RGI-C serve as co-primary endpoints, with a relaxed statistical threshold (p<0.2) for RGI-C. Enrollment in ENERGY 3 was completed in January 2025, with 27 pediatric patients enrolled. The trial’s 2:1 randomized design provides >90% power to detect meaningful differences in RGI-C between treatment and control groups. The 52-week treatment period is expected to conclude by January 2026, with topline data anticipated in the first quarter of 2026. About ENPP1 Deficiency ENPP1 Deficiency is a serious and progressive rare disease that affects blood vessels, soft tissues, and bones. Individuals who present in utero or in infancy are typically diagnosed with generalized arterial calcification of infancy (GACI Type 1), with about 50% of these infants not surviving beyond six months. Children with this condition typically develop autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adolescents and adults may develop osteomalacia, or softened bones. ARHR2 and osteomalacia cause pain and difficulty with movement. Additionally, patients may experience hearing loss, calcification in arteries and joints, and heart problems. ENPP1 Deficiency is an autosomal recessive disease and biallelic mutations are estimated to occur in approximately 1 in 64,000 pregnancies worldwide. Many individuals with just one copy of the mutated gene (monoallelic ENPP1 Deficiency) exhibit severe symptoms, suggesting that the worldwide prevalence of ENPP1 Deficiency may be much higher than current estimates. Currently, there are no approved therapies for ENPP1 Deficiency. About Inozyme Pharma Inozyme Pharma is a clinical-stage biopharmaceutical company dedicated to developing innovative therapeutics that target the PPi-Adenosine Pathway, a key regulator of bone health and blood vessel function. Disruptions in this pathway underlie a range of severe diseases, including ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis. Our lead investigational therapy, INZ-701, is an ENPP1 Fc fusion protein enzyme replacement therapy (ERT) designed to restore PPi and adenosine levels. INZ-701 is currently in late-stage clinical development in ENPP1 Deficiency, with the potential to expand into additional indications where deficiencies in the PPi-Adenosine Pathway contribute to disease pathology. Through our pioneering work, we aim to transform treatment options for patients affected by these devastating conditions. For more information, please visit https://www.inozyme.com/ or follow Inozyme on LinkedIn, X, and Facebook. Cautionary Note Regarding Forward-Looking Statements Statements in this press release about future expectations, plans, and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the initiation, timing, and design of our planned clinical trials, availability of data from clinical trials, the potential benefits of INZ-701, the potential for INZ-701 to be the first approved therapy for ENPP1 Deficiency, our regulatory strategy, and the period over which we believe that our existing cash, cash equivalents, and short-term investments will be sufficient to fund our cash flow requirements. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. 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 realize the anticipated cost savings related to the recent strategic prioritization and workforce reduction; conduct its ongoing clinical trials of INZ-701 for ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis; enroll patients in ongoing and planned trials; obtain and maintain necessary approvals from the FDA and other regulatory authorities; continue to advance its product candidates in preclinical studies and clinical trials; replicate in later clinical trials positive results found in preclinical studies and early-stage clinical trials of its product candidates; advance the development of its product candidates under the timelines it anticipates in planned and future clinical trials; obtain, maintain, and protect intellectual property rights related to its product candidates; manage expenses; comply with covenants under its outstanding loan agreement; and raise the substantial additional capital needed to achieve its business objectives. 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 in the Company's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, 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. Condensed Consolidated Balance Sheet Data(Unaudited)(in thousands) March 31,2025 December 31,2024Cash, cash equivalents and investments$84,776 $113,087 Total assets$95,164 $123,182 Total liabilities$63,366 $65,356 Additional paid-in-capital$447,790 $445,705 Accumulated deficit$(415,993) $(387,954)Total stockholders' equity$31,798 $57,826 Condensed Consolidated Statements of Operations and Comprehensive Loss(Unaudited)(in thousands, except share and per share data) Three Months Ended March 31, 2025 2024 Operating expenses: Research and development $20,379 $19,111 General and administrative 5,409 5,234 Restructuring charges 1,900 — Total operating expenses 27,688 24,345 Loss from operations (27,688) (24,345)Other income (expense): — — Interest income 1,117 2,374 Interest expense (1,406) (1,325)Other expense, net (62) (51)Other (expense) income, net (351) 998 Net loss $(28,039) $(23,347)Other comprehensive income (loss): Unrealized losses on available-for-sale securities (76) (156)Foreign currency translation adjustment 2 10 Total other comprehensive loss (74) (146)Comprehensive loss $(28,113) $(23,493)Net loss attributable to common stockholders—basic and diluted $(28,039) $(23,347)Net loss per share attributable to common stockholders—basic and diluted $(0.44) $(0.38)Weighted-average common shares outstanding—basic and diluted 64,278,527 61,772,279 ContactsInvestors:Inozyme PharmaStefan Riley, Senior Director of IR and Corporate Communications(617) 461-2442Stefan.riley@inozyme.com Media:Biongage CommunicationsTodd Cooper(617) 840-1637Todd@biongage.com A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/daff31dc-9507-47ff-98ef-67858da7835d

Clinical ResultExecutive ChangeFinancial Statement

07 May 2025

·www.fiercepharma.com

Sarepta tries to quell concerns over DMD gene therapy Elevidys as patients delay treatment after death report

As some Duchenne families have paused the treatment process, Sarepta warned that Elevidys’ sales in the second quarter could be as much as 20% lower than in the first quarter. Sarepta Therapeutics CEO Doug Ingram opened the company’s first-quarter earnings call Tuesday by acknowledging that, like the broader biopharma industry, the genetic medicine biotech is facing a challenging time.Following report of a patient’s death after treatment with Sarepta’s Duchenne muscular dystrophy gene therapy Elevidys, some families have paused the treatment process to seek additional information, Ingram said on the call.Patient hesitation, coupled with a severe flu season and administrative delays at some treatment sites, caused Elevidys to miss sales expectations. The drug delivered $375 million in sales during the first quarter, a 2% sequential decline and 11% below analysts’ consensus estimate.As a result of these trends, Sarepta’s Chief Customer Officer Dallan Murray warned that Elevidys’ sales in the second quarter could be as much as 20% lower than in the first quarter.Sarepta has also dialed back its total 2025 revenue projection to a range between $2.3 billion and $2.6 billion exclusively because of lower Elevidys expectations, Ingram said. The company’s previous guidance was $2.9 billion to $3.1 billion, including $900 million in sales from its other DMD drugs Exondys 51, Vyondys 53 and Amondys 45.However, Murray stressed that the company expects “only a temporary impact,” and that its long-term demand outlook for the one-time gene therapy “remains strong.” Ingram also noted that patient start forms are still coming in from both ambulatory and nonambulatory patients.In March, Sarepta disclosed that a 16-year-old patient had passed away after developing acute liver failure following Elevidys treatment and a recent cytomegalovirus infection, which can infect and damage the liver. Elevidys, like other adeno-associated virus (AAV) vector-based gene therapies, comes with a liver toxicity risk. But the death was the first among more than 800 patients who have received the Duchenne therapy in clinical trials or in the commercial setting.“We are continuing to explore what was uniquely different about this case than every of the other hundreds and hundreds of infusions that have occurred to date,” Ingram said.The company has not received the autopsy report but expects it in the next month or two, according to Ingram. Sarepta has submitted a request to the FDA to include the death case in Elevidys’ label, and the agency plans to review the situation by the end of the year, Sarepta’s R&D chief, Louise Rodino-Klapac, Ph.D., said on the call.Data so far suggest no difference in the rates of adverse events in relationship to age or weight, Rodino-Klapac said. No relationships have been identified between liver safety signals and the total Elevidys dose administered, or patient age or weight.Top experts in the DMD field have not changed their treatment approach and there are still families who view the benefit-risk profile of Elevidys positively, Ingram said. About 60% of Elevidys revenue comes from top sites and experts, many of whom are already fully booked out to 12 months, he noted, adding that the company needs to direct much of its attention to other sites with more available capacity.But the hesitation in the broader DMD community is obvious.Following the incident, Sarepta “immediately initiated extensive outreach” to doctors and the DMD community to educate them about Elevidys’ data, Murray said.“Our current focus is on disseminating this information across the wider treating and referring physician landscape, which is a process that takes time,” he said.Despite the unfortunate death, Elevidys still has “one of the most impressive safety profiles” of AAV-based gene therapies, Ingram said.The chief executive also argued that the safety signal should be interpreted in the context of Elevidys’ efficacy profile. Two-year MRI results unveiled in January showed that patients treated with the drug had minimal muscle pathology progression. Patients who had originally been treated with placebo, who then crossed over to receive Elevidys, showed statistically significant and clinically meaningful functional benefit across several Duchenne tests compared with an external control group. However, one analyst raised an investor concern about a worst-case scenario in which Elevidys is pulled from the market. And the appointment of long-time biopharma industry skeptic Vinay Prasad, M.D., as the new leader for the FDA’s Center for Biologics Evaluation and Research does not help with that narrative, the analyst noted.Ingram wouldn’t comment on Prasad’s appointment.“What I do remain confident about is that the FDA is going to be the FDA that had been for the last 100 years, which is an organization dedicated to following great science and fulfilling its mission of bringing life-enhancing therapies that are safe and efficacious to patients,” he said.

06 May 2025

·www.fiercebiotech.com

Capricor shares turn red as FDA plans deramiocel adcomm, likely the first under new commissioner

The date for the adcomm has not yet been set. \n Capricor Therapeutics saw its shares fall 13% by the end of trading Monday as its investigational cell therapy deramiocel for DMD was revealed as the first drug expected to face an FDA advisory committee under the new agency’s commissioner, Marty Makary, M.D.Capricor’s previously announced PDUFA date of August 31 remains, but the biotech said in a release Monday that the FDA is also now asking for an advisory committee (adcomm) to discuss the data for its Duchenne muscular dystrophy (DMD) hopeful deramiocel.No date has been assigned for the adcomm, though the event will need to occur before the PDUFA date. This is expected to be the first such committee to meet under the auspices of the new Trump administration’s FDA commissioner, Makary.Shares in the biotech fell more than 13% by the end of trading Monday, likely caused by investor jitters over the drug being the subject of the first adcomm under the Trump administration, as well as the FDA\'s request for an adcomm in the first place. The FDA can eschew the need for such reviews and sometimes its need for one can be seen as a negative.Capricor CEO Linda Marbán, Ph.D., for her part, framed the development as progress toward a potential approval.“The successful completion of our mid-cycle review meeting along with the upcoming advisory committee meeting represents major milestones on the path towards approval of deramiocel,” Marbán said in a statement.“We have been actively preparing for an advisory committee meeting, and we look forward to providing the physician and patient perspectives to highlight the weight of evidence supporting the transformative potential of deramiocel in treating DMD-cardiomyopathy,\" Marbán added.While some Capricor investors appeared caught off guard, the adcomm request is not too surprising. For one, DMD has been a bête noire for the FDA over the years since the controversial approval in 2016 of a Sarepta therapy for the condition.That drug, Exondys 51, won an FDA thumbs-up nine years ago based on dystrophin production data, but without showing actual clinical benefits such as improvements in disease progression measures. Opinions were split even within the FDA; in fact, two officials who\'d opposed the green light decided to retire. In contrast, European regulators shot down Exondys 51 twice around the same period.In 2019, the agency also gave an accelerated approval to Sarepta’s follow-on DMD drug Vyondys 53, just months after turning it down in what was an unexpected reversal, causing yet more controversy.Capricor’s drug is a next-gen form of cell therapy in DMD, also likely prompting the FDA to convene its outside committee of experts. Data for the therapy, which is up for a full approval in patients with DMD cardiomyopathy, come from the biotech’s phase 2 HOPE-2 and HOPE-2 open-label extension (OLE) tests.Last fall, the latter trial showed that after three years, deramiocel improved DMD patients’ left ventricular ejection fraction and their ability to use their upper limbs.The trial was small, enrolling just 13 patients, with a deramiocel infusion given every three months. Capricor had previously reported that the treatment met the trial’s main goal in 2021.There were, however, some safety issues within the trial: All 13 patients in the OLE test experienced a mild to moderate adverse event, with five also experiencing a severe or life-threatening event. Nine of the 13 events were related to the treatment, Capricor reported in its presentation last October. DMD is a rare genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin that helps keep muscle cells intact. It typically affects boys from a young age and can dramatically reduce life expectancy without treatment.Deramiocel works as an allogeneic cell therapy of cardiosphere-derived cells, which are connective tissue cells from the heart. The cells secrete tiny cargo packets called exosomes, which target macrophages and alter their behavior so that they become anti-inflammatory and pro-tissue regeneration.“Deramiocel is a first-in-class cellular therapy with the potential to halt or slow the progression of DMD-cardiomyopathy, and we are pleased to have the opportunity to present the efficacy and safety data to the advisory committee,\" Marbán said.

Cell TherapyPhase 2Accelerated ApprovalDrug ApprovalClinical Result

100 Deals associated with Eteplirsen

External Link

KEGG	Wiki	ATC	Drug Bank
D09900	Eteplirsen	M09AX06	DB06014

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Muscular Dystrophy, Duchenne	United States	Sarepta Therapeutics, Inc.	19 Sep 2016

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04179409 (CTgov)	Phase 2	Muscular Dystrophy, Duchenne	3	Amondys 45 (AMONDYS 45)	qccwgndhim(nxstgxrtas) = tgshnvmjaz cxlupkezcq (yxtzdgiawx, 1.8) View more	-	12 Oct 2023
				Exondys 51 (EXONDYS 51)	kuezffaukt(dazrbbmlvx) = fuxxqkoroq sdrapnohtq (kknurlmtlz, miggdwmqpt - plhtuqhyhf) View more
NCT03985878 (CTgov)	Phase 2	Muscular Dystrophy, Duchenne	15	Eteplirsen	effxmcddgg = wuielizeku vsnpdexikq (jncgjrucvq, bivfhdmvff - dctitnobcn) View more	-	18 Aug 2023
MDA2023	Not Applicable	Muscular Dystrophy, Duchenne	579	Eteplirsen-treated patients	hljoptqjor(vxtgvxpzua) = 5.4 years ksxfzwwiwb (zdrrffgpmd )	-	19 Mar 2023
				Eteplirsen
MDA2021	Not Applicable	Muscular Dystrophy, Duchenne genetic mutations amenable to exon 51 skipping	-	Eteplirsen	nqmkaglepu(usuafvqxxs) = cixmxrlczc daexhniicm (asskaszbzg )	-	01 Mar 2021
				Eteplirsen	nqmkaglepu(usuafvqxxs) = knzksbjdgp daexhniicm (asskaszbzg )
NCT00159250 (CTgov)	Phase 1/2	Muscular Dystrophy, Duchenne	7	AVI-4658 (Low Dose AVI-4658)	iangdpxhri = fumkauczbq zrfahivsaj (efqavyiwpi, rfolduvsew - bmygbllkdb) View more	-	05 Dec 2019
				AVI-4658 (High Dose AVI-4658)	iangdpxhri = vuozmezoqa zrfahivsaj (efqavyiwpi, usstorlkcm - tpphpqveqh) View more
NCT01540409 (CTgov)	Phase 2	Muscular Dystrophy, Duchenne	12	Eteplirsen (Eteplirsen 30 mg/kg)	gwthxmojjt(igmuiafjtd) = rmrfdazidt zuzyxgiwhz (pkpwmtfuii, 113.25) View more	-	10 Jul 2019
				Eteplirsen (Eteplirsen 50 mg/kg)	gwthxmojjt(igmuiafjtd) = afgepskmjq zuzyxgiwhz (pkpwmtfuii, 175.65) View more
NCT02286947 (CTgov)	Phase 2	Muscular Dystrophy, Duchenne	24	Eteplirsen	bwozvyfwtb = vbttmyatir sdvmlrhpcz (tbottkktta, xxpbuoilgx - jnmjtyxmnj) View more	-	20 Feb 2019
Study 204 (ANA2018)	Phase 2	-	24	All CINRG cohort	doeubtlvdx(eqceqhcusx) = yxivsiugoi dnuhjlebsk (yewgpifxqd )	Positive	05 Oct 2018
				Genotyped CINRG cohort	doeubtlvdx(eqceqhcusx) = cnfkxvfolw dnuhjlebsk (yewgpifxqd )
S42.008 (AAN2017)	Phase 3	Muscular Dystrophy, Duchenne whole exon deletions in the dystrophin gene	150	Eteplirsen 30 mg/kg/wk IV	zzcvwglitc(rxrbztsdlt) = kptkdspgdx eofbjmmjds (skxztnbggt ) View more	Positive	18 Apr 2017
				Eteplirsen 50 mg/kg/wk IV	zzcvwglitc(rxrbztsdlt) = nsqtadfddk eofbjmmjds (skxztnbggt ) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis