Pamrevlumab for the treatment of DMD

FibroGen receives Fast Track designation from the U.S. FDA for Pamrevlumab to treat Duchenne muscular dystrophy (DMD).

 

FibroGen, Inc. announced that the U.S. Food and Drug Administration (FDA) had granted Fast Track designation for its anti-CTGF antibody, pamrevlumab, for the treatment of patients with Duchenne muscular dystrophy (DMD). This designation follows a review of Phase 2 clinical data from a single-arm trial in non-ambulatory patients with DMD. It represents recognition by the FDA that pamrevlumab has the potential to address an unmet medical need for this disease. Pamrevlumab is currently being evaluated in two Phase 3 trials for the treatment of DMD.

 

Mark Eisner, M.D, M.P.H, Chief Medical Officer, FibroGen – “Fast Track designation by the FDA for pamrevlumab in DMD underscores the high unmet medical need for patients suffering from this debilitating disease and potential to advance a new treatment option. We look forward to working closely with the FDA on the development of pamrevlumab as a potential therapy for DMD.”

 

About Fast Track designation

Fast Track designation is intended to facilitate the development and review of drugs used to treat serious conditions and fill an unmet medical need. Fast Track designation enables the company to have more frequent interactions with the FDA throughout the drug development process so that an approved product can reach the market expeditiously. Read more.

About Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a rare and debilitating neuromuscular disease that affects approximately 1 in every 5,000 newborn boys. About 20,000 children are diagnosed with DMD globally each year. The fatal disease is caused by a genetic mutation leading to the absence or defect of dystrophin, a protein necessary for normal muscle function—the absence of dystrophin results in muscle weakness, muscle loss, fibrosis, and inflammation. Patients with DMD are often wheelchair users before the age of 12, and their progressive muscle weakness may lead to serious medical problems relating to respiratory and cardiac muscle. Learn more here.

About Pamrevlumab

Pamrevlumab is a first-in-class antibody developed by FibroGen that inhibits the activity of connective tissue growth factor (CTGF), an important biological mediator in fibrotic and proliferative disorders. Pamrevlumab is in Phase 3 clinical development for the treatment of locally advanced unresectable pancreatic cancer (LAPC), Duchenne muscular dystrophy (DMD), and idiopathic pulmonary fibrosis (IPF). For information about pamrevlumab studies currently recruiting patients, please visit www.clinicaltrials.gov.

About FibroGen

FibroGen, Inc. is a biopharmaceutical company committed to discovering, developing, and commercializing a first-in-class therapeutics pipeline. The Company applies its pioneering expertise in hypoxia-inducible factor (HIF) and connective tissue growth factor (CTGF) biology to advance innovative medicines to treat unmet needs. The Company is currently developing and commercializing roxadustat, an oral small-molecule inhibitor of HIF prolyl hydroxylase activity, for anemia associated with chronic kidney disease (CKD). Roxadustat is also in clinical development for anemia associated with myelodysplastic syndromes (MDS) and chemotherapy-induced anemia (CIA). Pamrevlumab, an anti-CTGF human monoclonal antibody, is in clinical development for the treatment of locally advanced unresectable pancreatic cancer (LAPC), Duchenne muscular dystrophy (DMD), and idiopathic pulmonary fibrosis (IPF). For more information, please visit www.fibrogen.com.

Solid Biosciences reports efficacy and safety data

Solid Biosciences reports efficacy and safety data from the ongoing IGNITE DMD clinical trial and resumption of patient dosing in the 2E14 VG/kg cohort.

La Force is sharing this press release provided by Solid Biosciences, March 15, 2021, original press release

  • Interim data from six patients provide evidence of a potential benefit of SGT-001 in functional endpoints of North Star Ambulatory Assessments (NSAA), 6-minute walk test (6MWT), pulmonary function tests (PFTs), and clinically validated patient-reported outcome measures (PROMs)
  • Patient 7, safely dosed with SGT-001, experienced transient and manageable adverse events, none of which were serious; six patients previously dosed showed no new drug-related safety findings 17-37 months post-dosing; screening and enrollment of patients into IGNITE DMD continue.

Solid Biosciences Inc., a life sciences company focused on advancing meaningful therapies for Duchenne muscular dystrophy, reported encouraging interim functional (NSAA, 6MWT and PFTs) and biomarker data, and patient-reported outcome measures (PROMs) from six patients after treatment in the ongoing IGNITE DMD Phase I/II clinical trial of its lead gene therapy candidate, SGT-001. The Company also announced that patient 7 in IGNITE DMD was safely dosed, with transient and manageable adverse events, none of which were serious. Patient 7 was the first patient dosed in IGNITE DMD under a previously reported clinical protocol amendment and using SGT-001 manufactured with its second-generation process. The six patients previously dosed showed no new drug-related safety findings, 17-37 months post-dosing. The totality of data collected, and the re-initiation of dosing, support the continued enrollment of patients into the IGNITE DMD study.  

These data will also be presented in an oral session and at a company-sponsored symposium at the 2021 MDA Virtual Clinical & Scientific Conference on Thursday, March 18.

 

Barry Byrne, M.D., Ph.D., Associate Chair of Pediatrics and Director of the Powell Gene Therapy Center at the University of Florida, and Principal Investigator of the IGNITE DMD clinical study – The totality of the functional and biomarker data, as well as the patient-reported outcome measures, reported today to suggest that SGT-001 may provide benefit to patients with Duchenne, a serious disease for which there is no cure. I am particularly encouraged by these early data when compared with the natural history of this disease. I look forward to the continued enrollment in IGNITE DMD and evaluating the data as the study progresses.

 

Ilan Ganot, Chief Executive Officer, President and Co-Founder of Solid Biosciences – We are encouraged with the successful resumption of dosing in the IGNITE DMD trial under our amended clinical protocol and using SGT-001 manufactured with a second-generation process. The seventh patient’s safe dosing gives us increased confidence in our dosing strategy as we move forward with clinical development in the IGNITE DMD clinical trial. We are grateful to this patient and his family and all those who choose to participate in clinical trials. We look forward to continuing to dose patients and reporting clinical outcomes from additional patients in the second half of 2021.

 

IGNITE DMD Data

The data reported were collected from the first six patients dosed in IGNITE DMD 12 to 24 months after treatment and include data from three patients dosed at the low dose (5E13 VG/kg) and three patients dosed at the high dose (2E14 VG/kg). Data from the delayed treatment cohort, analyzed as an untreated control cohort, were evaluated alongside representative natural history data. The six patients ranged in age from five to 14-years-old at baseline. These data have been previously shared with the FDA and members of the IGNITE DMD Data Safety Monitoring Board and clinical consultants.

Functional Data

  • Among patients in the low and high dose cohorts, North Star Ambulatory Assessment (NSAA) scores at one year suggest benefit after treatment as compared to trajectories typically observed in natural history data. Natural history analyses suggest that patients similarly aged to those enrolled in IGNITE DMD would normally be expected to exhibit year-over-year disease progression ranging from a plateau in gains to a 3 to 3.7-point decline. Patients in the untreated control cohort exhibited a mean decline of 4.0 points from baseline to 1 year. In contrast, patients in the low-dose cohort exhibited a mean improvement of 1.0 point over the same period of time. Patients in the high-dose cohort exhibited a mean improvement of 0.3 points as compared to their baseline values.
  • Mean increase in the 6-Minute Walk Test (6MWT) distance was above the generally accepted minimally clinically important difference (MCID) of 30 meters in both the low- and high-dose cohorts after treatment. While patients in the untreated control cohort exhibited a decline of 8.5 meters from baseline to one year, patients in the low-dose cohort exhibited a mean improvement of 37 meters. Patients in the high-dose cohort exhibited an improvement of 49.7 meters over the same period.
  • Concerning pulmonary function tests (PFTs), most patients in both dose groups exhibited improved forced vital capacity (% predicted FVC) at one year when declines in pulmonary function would otherwise be typically observed in patients with Duchenne. From baseline to one year, patients in the untreated control cohort exhibited a mean decline of 10.7% on an absolute basis. In contrast, patients in the low-dose and high-dose cohorts exhibited a mean improvement of 3.9% and 16.7%, respectively, over the same period.

Biomarker Data

  • As previously reported, biopsies of skeletal muscle three months after a single infusion of SGT-001 at a dose of 2E14vg/kg demonstrated the widespread distribution of microdystrophin-positive muscle fibres with co-localization of neuronal nitric oxide synthase (nNOS) and β-sarcoglycan in the muscles of these patients.
  • Creatine kinase (CK) assessments of the six patients provide potential physiological evidence of a positive or stabilizing effect after one year of treatment with a single high-dose infusion of SGT-001. An average sustained CK decline of approximately 50% in patients in the high-dose cohort was observed. In the low-dose cohort, an average CK increase of approximately 166% was observed, and in the control group, an average CK increase of approximately 17% was observed.

Patient Reported Outcome Measures (PROMs) Data

Patient reported outcome measures taken after one year of treatment revealed a trend towards dose-ordered improvements in motor function subscales and fatigability assessments, providing real-world evidence to support the clinical and biomarker findings of varying degrees of benefit to patients in the low- and high- dose cohorts.

  • Meaningful improvements were demonstrated in the Pediatric Outcomes Data Collection Instrument (PODCI), a validated PROM that contains questions to assess how caregivers and children evaluate the child’s ability to walk, stand, and perform daily living, as well as recreational activities. Motor function scores reflect the gains seen in 6MWT and the benefit of NSAA observed in all dosed patients.
  • Semi-structured, qualitative interviews conducted by Modus Outcomes Ltd with patients and caregivers about the impact of Duchenne on functioning demonstrated overall improvement in the functional activity and school-related impacts (e.g., lower limb mobility, keeping up with peers, climbing stairs, sports) in low- and high-dose cohorts, with subjective decreased fatigability in all patients of both treatment cohorts.

As previously reported, three of the first six patients dosed before the protocol amendments introduced in 2020 developed four serious adverse events (SAEs). All prior SAEs have fully resolved, and no new drug-related safety findings have been identified with post-dosing follow-up of 17-37 months. Additionally, as reported today, with the resumption of dosing in IGNITE DMD, patient 7 was dosed safely with mild to moderate adverse events, all of which have fully resolved. The resumption of dosing was under an amended clinical protocol and using SGT-001 manufactured with an improved process, both designed to enhance patient safety.

 

About SGT-001

Solid’s SGT-001 is a novel adeno-associated viral (AAV) vector-mediated gene transfer therapy designed to address the underlying genetic cause of Duchenne. Duchenne is caused by mutations in the dystrophin gene that result in the absence or near absence of dystrophin protein. SGT-001 is a systemically administered candidate that delivers a synthetic dystrophin gene, called microdystrophin, to the body. This microdystrophin encodes for a functional protein surrogate expressed in muscles and stabilizes essential associated proteins, including neuronal nitric oxide synthase (nNOS). Data from Solid’s clinical program suggests that SGT-001 has the potential to slow or stop the progression of Duchenne, regardless of genetic mutation or disease stage.

SGT-001 is based on pioneering research in dystrophin biology by Dr. Jeffrey Chamberlain of the University of Washington and Dr. Dongsheng Duan of the University of Missouri. SGT-001 has been granted Rare Pediatric Disease Designation, or RPDD, and Fast Track Designation in the United States and Orphan Drug Designations in both the United States and European Union.

In case you don’t remember the specifics about microdystrophin and gene therapy we invite you to watch the interview we conducted in London with Dr. Jeffrey Chamberlain PH.D.:  Here

 

About Solid Biosciences

Solid Biosciences is a life sciences company focused on advancing transformative treatments to improve patients’ lives with Duchenne. Disease-focused and founded by a family directly impacted by Duchenne, our mandate is simple yet comprehensive – work to address the disease at its core by correcting the underlying mutation that causes Duchenne with our lead gene therapy candidate, SGT-001. For more information, please visit www.solidbio.com.

 

About DMD

Duchenne muscular dystrophy (DMD) is a disease that almost exclusively affects boys and whose incidence is 1 in 3,500. It is extremely rare that Duchenne muscular dystrophy (DMD) will affect girls. Those affected are usually diagnosed around the age of five, but symptoms may be visible from early childhood. It is a degenerative disease of the muscles caused by a genetic mutation. The Duchenne muscular dystrophy (DMD) – for which no treatment is currently available – directly affects skeletal muscles. Without treatment, the consequences of the disease are dire for those afflicted and their families.

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News from Vamorolone in Duchenne Muscular Dystrophy

Santhera Announces Completion of First 6-Month Period of Pivotal VISION-DMD Trial with Vamorolone in Duchenne Muscular Dystrophy

Original Press release > Pratteln, Switzerland, March 3, 2021

Santhera Pharmaceuticals announces that the last patient has completed the last visit for the first period of the placebo-controlled pivotal VISION-DMD study with vamorolone in patients with Duchenne muscular dystrophy (DMD), conducted by partner ReveraGen Biopharma Inc. Subject to a positive 6-month topline data readout of this first study phase, this could allow for regulatory submission to the US FDA in Q1-2022 with the potential to offer an alternative to the current standard of care in DMD.

The 48-week Phase 2b VISION-DMD study is designed as a pivotal trial to demonstrate the efficacy and safety of vamorolone administered orally versus prednisone and placebo in ambulant boys aged 4 to <7 years with DMD. Efficacy outcome measures are motor function and strength outcomes with the Time to Stand test (TTSTAND) as the primary study endpoint. Additional analyses compare safety and tolerability between the vamorolone dose groups, placebo and prednisone. In the now completed 24-week, placebo- and active-controlled treatment period, patients were randomized to receive vamorolone 2.0 mg/kg/day, vamorolone 6.0 mg/kg/day, prednisone 0.75 mg/kg/day or matching placebo. For the second treatment period of another 24 weeks of continued study conduct, patients who previously received prednisone or placebo have been randomized and will be switched to one of two doses of vamorolone. This treatment period where all patients receive vamorolone is evaluating the persistence of effect in the longer term. In addition to efficacy, the study aims to confirm the differentiated safety and favourable tolerability profile of vamorolone with the potential to offer an alternative to the current standard of care. Although glucocorticoids are part of DMD’s current care recommendations, their adverse effect profile limits their use as chronic therapy.

 

Eric Hoffman, Ph.D., President and CEO at ReveraGen BioPharma – “We are delighted about having achieved this important milestone and are looking forward to announcing the topline 6-month results of this pivotal study together with Santhera. The use of glucocorticoids, despite having proven benefits in the treatment of DMD, is severely limited due to side effects and poor tolerability. Our expectation is that vamorolone will have the benefits but avoids many of the tolerability issues that limit the use of this standard of care. Our thanks go out to the study participants, their families and healthcare professionals who, in the midst of the COVID-19 pandemic, are enabling us to advance this pivotal study as intended.”

 

Dario Eklund, CEO of Santhera – “Based on previously established data, we believe that vamorolone has the potential to become a foundational therapy in DMD for patients irrespective of the underlying gene mutation and a promising alternative to existing corticosteroids. Our organization is wholeheartedly dedicated to bringing this novel therapy to patients who are hoping for a DMD therapy with fewer treatment-limiting side effects, making it suitable for longer-term administration and also improving quality of life.”

 

 

About Vamorolone – first-in-class dissociative steroid

Vamorolone is a first-in-class drug candidate that binds to the same receptors as corticosteroids but modifies the receptors’ downstream activity. This has the potential to ‘dissociate’ efficacy from typical steroid safety concerns and, therefore, could replace existing corticosteroids, the current standard of care in children and adolescent patients with DMD. There is a significant unmet medical need in this patient group as high-dose corticosteroids have severe systemic side effects that detract from treatment compliance and patient quality of life.

In the pivotal Phase 2b VISION-DMD trial, the last patient has completed the last visit of the 24-week, placebo- and active-controlled treatment period. Topline 6-month data are expected in Q2-2021, paving the way for a US NDA submission in Q1-2022. Vamorolone has been granted Orphan Drug status in the US and Europe and has received Fast Track and Rare Pediatric Disease designations by the US FDA and Promising Innovative Medicine (PIM) status UK MHRA. Vamorolone was discovered by US-based ReveraGen BioPharma Inc. and is being developed in collaboration with Santhera, which owns worldwide rights to the drug candidate in all indications. The vamorolone development program has received funding from several international non-profit foundations and patient organizations, the US National Institutes of Health, the US Department of Defense and the European Commission’s Horizon 2020 program.

Clinical trial in Canada

 

About Santhera

Santhera Pharmaceuticals is a Swiss specialty pharmaceutical company focused on developing and commercializing innovative medicines for rare neuromuscular and pulmonary diseases with a high unmet medical need. Santhera is building Duchenne muscular dystrophy (DMD) product portfolio to treat patients irrespective of causative mutations, disease stage or age. A marketing authorization application for Puldysa® (idebenone) is currently under review by the European Medicines Agency. Santhera has an option to license vamorolone, a first-in-class dissociative steroid presently investigated in a pivotal study in patients with DMD to replace standard corticosteroids. Santhera out-licensed ex-North American rights to its first approved product; for further information, please visit www.santhera.com.

 

About ReveraGen BioPharma

ReveraGen was founded in 2008 to develop first-in-class dissociative steroidal drugs for Duchenne muscular dystrophy and other chronic inflammatory disorders. The development of ReveraGen’s lead compound, vamorolone, has been supported through partnerships with foundations worldwide, including Muscular Dystrophy Association USAParent Project Muscular DystrophyFoundation to Eradicate DuchenneSave Our SonsJoiningJackAction DuchenneCureDuchenneRyan’s QuestAlex’s WishDuchenneUKPietro’s FightMichael’s Cause, and Duchenne Research Fund. ReveraGen has also received generous support from the US Department of Defense CDMRP, National Institutes of Health (NCATS, NINDS, NIAMS), and European Commission (Horizons 2020).

 

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Italfarmaco provides an update on Givinostat

Italfarmaco provides an update on Givinostat, an ongoing clinical program, in an oral presentation at XVIII International Conference on Duchenne and Becker Muscular Dystrophy.

Feb. 22, 2021, > Original press release on Business Wire <

  • Analyses of long-term study with Givinostat in Duchenne muscular dystrophy boys continue to show delayed disease progression
  • EPYDIS Phase 3 pivotal clinical trial continues as planned, with preliminary results expected in the second quarter of 2022

The Italfarmaco Group announced updates on its clinical development programs with Givinostat, its proprietary histone deacetylase (HDAC) inhibitor, in boys with Duchenne Muscular Dystrophy (DMD), at the virtual XVIII International Conference on Duchenne and Becker Muscular Dystrophy. In the presentation made on February 20, 2021, Paolo Bettica, MD, Ph.D., Chief Medical Officer at the Italfarmaco Group, provided evidence that continues to show a delay in disease progression in DMD boys aged 7-11 years at treatment start, supported by data on the 7-year follow-up period from the long-term study with Givinostat in addition to steroid treatment.

 

Dr. Paolo Bettica – “We are very encouraged to see that the long-term study with Givinostat continues to show a benefit in boys with DMD, which further supports its potential as a treatment. Our Phase 3 pivotal clinical study is on track and continues as planned with 179 boys recruited, and we look forward to announcing the results in the second quarter of next year. We have made significant progress despite the pandemic and instituted procedures to ensure the safety and well-being of all trial participants while being able to continuously provide access to the study drug, as well as to maintain the scientific validity and integrity of the trial. We are grateful to the clinical teams conducting the studies in all of the sites for continuing to work for the benefit of the participants.”

 

The on-going, long-term study (ClinicalTrials.gov: NCT03373968) with Givinostat in boys with DMD is an extension of its Phase 2 trial (ClinicalTrials.gov: NCT01761292). The new follow-up analyses* after more than 7 years of treatment show that the mean age at loss of ambulation in DMD boys treated with Givinostat on top of corticosteroids is 16.0 years contrasted to the one in the Cooperative International Neuromuscular Research Group (CINRG) study, which was 13.4 years (Mc Donald et al., Lancet 2017). Moreover, the yearly rate of change of respiratory parameters such as Forced Vital Capacity % Predicted (FVC%) and Peak Expiratory Flow % predicted (PEF%) is -1.7% and 0% in contrast to the 4 to 6% yearly rate of decline in these parameters as demonstrated in natural history studies of a patient population comparable to the Givinostat cohort (Mayer et al., Paediatr Pulmonol 2015; Henricson et al., Muscle Nerve 2013; Abresch et al., Neuromuscul Disord 2013; Kinane et al., Journal of Neuromuscular Diseases 2018).

 

Prof. Eugenio Mercuri, Professor of Paediatric Neurology at the Catholic University, Rome, Italy, commented on these results, “Overall these results suggest a potential long-term beneficial effect of Givinostat in DMD boys. We look forward to the final results and remain hopeful that these results can support the registration of Givinostat for the treatment of DMD.”

 

In October 2020, the U.S. Food and Drug Administration (FDA) granted a Rare Pediatric Disease designation to Givinostat to treat DMD, which allows an expedited review process for new treatment modalities. The company also received an Orphan Drug designation and Fast Track designation for Givinostat from the FDA.

About Givinostat

Givinostat is an investigational drug discovered through Italfarmaco’s internal research and development efforts in collaboration with Lorenzo Puri (Santa Lucia Foundation, Rome) and his team and partnerships with Telethon and Parent Project aps. It is being evaluated for safety and efficacy for the treatment of Duchenne – and Becker – Muscular Dystrophy. Givinostat inhibits histone deacetylases (HDACs). HDACs are enzymes that prevent gene translation by changing the three-dimensional folding of DNA in the cell. Studies show that Duchenne patients have higher than normal HDAC levels, which may prevent muscle regeneration and trigger inflammation. In the company’s clinical study in DMD boys aged seven to less than 11 years, Givinostat was observed to slow disease progression, significantly increase muscle mass and reduce the amount of fibrotic tissue. Givinostat treatment also significantly reduced muscle tissue necrosis and fatty replacement, two additional parameters related to disease progression (Bettica et al., Neuromuscular Disorder 2016).

About Italfarmaco Group

Italfarmaco is a specialty pharmaceutical company engaged in discovering, developing, manufacturing, and marketing branded prescription and nonprescription products in more than 60 countries on 5 continents. Italfarmaco’s research and development expertise is best demonstrated through its HDAC inhibitor development programs, addressing new therapeutic treatments of specialty and rare diseases. Italfarmaco is dedicated to serving patients whose needs remain largely unmet through marketed drugs and compounds in development. italfarmaco.com

*The results of these analyses are not published yet.

Canadian study locations

  • Canada, Alberta: Kinsmen Research Centre – Alberta Children’s Hospital – Alberta Health Services
  • Canada, British Columbia: The University of British Columbia, Children’s and Women’s Health Centre of BC Branch
  • Canada, Ontario: Holland Bloorview Kids Rehabilitation Hospital
  • Read more on ClinicalTrials.gov

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff.

About Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a disease that almost exclusively affects boys and whose incidence is 1 in 3,500. Duchenne muscular dystrophy (DMD) will rarely affect girls. Those affected are usually diagnosed around five, but symptoms may be visible from early childhood. It is a degenerative disease of the muscles caused by a genetic mutation. The Duchenne muscular dystrophy (DMD) – for which no treatment is currently available – directly affects skeletal muscles. Without treatment, the consequences of the disease are dire for those afflicted and their families. Read more here.

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Sarepta announces top-line results for its investigational gene therapy

Sarepta Therapeutics announces top-line results for part 1 of study 102 evaluating SRP-9001, its investigational gene therapy for the treatment of Duchenne muscular dystrophy (DMD)

 

Jan. 7, 2021, >Original press release<

Sarepta Therapeutics, Inc. announced top-line results from Part 1 of Study SRP-9001 (Study 102), an ongoing, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety, efficacy and tolerability of a single dose of SRP-9001 (rAAVrh74.MHCK7.micro-dystrophin) in 41 patients with Duchenne muscular dystrophy. SRP-9001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein.

Quickly

  • The study met the primary biological endpoint of micro-dystrophin protein expression at 12 weeks post-treatment, measured by western blot, in SRP-9001-treated participants versus placebo.
  • SRP-9001-treated participants showed an increase in NSAA total score compared to placebo at 48 weeks; however, the study did not achieve statistical significance on the primary functional endpoint of improvement in NSAA total score compared to placebo at 48 weeks post-treatment  
  • In the pre-specified analysis by age-group, by which the randomization was stratified, participants aged 4-5 years at the time of treatment with SRP-9001 demonstrated a statistically significant improvement in NSAA total score age-matched placebo cohort, achieving a 4.3-point improvement on NSAA at 48 weeks post-treatment from baseline.
  • No new safety signals were identified for SRP-9001, reinforcing the favourable safety profile observed to date.

Study 102 is ongoing and remains blinded to participants, investigators, site staff and sponsor staff with direct site interaction. All 41 participants have completed their Part 1, 48-week assessment and have entered the Part 2 crossover phase. Participants continue to be monitored for safety and will undergo another biopsy at week 12 in Part 2 to assess the expression and biological markers, in addition to longer-term assessments of functional outcomes.

 

Doug Ingram, president and chief executive officer, Sarepta – “Study 102 reinforces our confidence in the potentially transformative benefits of SRP-9001, including among other things, the fact that in the Study’s pre-specified analysis, the participants in the 4-5 age group robustly achieved a statistically significant and clinically meaningful improvement in NSAA over placebo, as predicted by our prior Study 101. For the entire population, while we saw separation at every time point between the active and placebo cohorts, Study 102 did not achieve statistical significance on the primary functional endpoint. In this regard, we are very disappointed that the randomization process resulted in a significant imbalance in baseline NSAA scores between the active and placebo cohorts of the participants ages 6-7, making the 6-7 age groups non-comparable and likely substantially contributing to the inability to achieve statistical significance. Study 102 remains blinded and we will analyze the functional results for all patients, including cross-over participants, once they have achieved the 48-week timepoint in Part 2. We have already enrolled and dosed 11 participants in Study 103, using our commercial process material, and we will have biomarker and safety results from that cohort in the second quarter. And very importantly, Study 102 has provided us with a wealth of information and insight which we will use to refine and complete the protocol for our upcoming trial using commercial process material. We intend to continue to move forward with diligence and urgency to generate the evidence necessary to bring SRP-9001 to waiting Duchenne patients around the world.”

 

*The NSAA is a 17-item rating scale used to measure functional motor abilities in ambulant children with Duchenne. It is used to monitor the disease’s progression and treatment effects, which makes it suitable as an endpoint in clinical trials for Duchenne.

About Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a rare, fatal neuromuscular genetic disease in approximately one in every 3,500-5,000 males worldwide. DMD is caused by a change or mutation in the gene that encodes instructions for dystrophin. Symptoms of DMD usually appear in infants and toddlers. Affected children may experience developmental delays such as difficulty in walking, climbing stairs or standing from a sitting position. As the disease progresses, muscle weakness in the lower limbs spreads to the arms, neck and other areas. Most patients require full-time use of a wheelchair in their early teens and then progressively lose the ability to independently perform daily living activities such as using the restroom, bathing and feeding. Eventually, increasing breathing difficulty due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and patients usually succumb to the disease in their twenties.

About SRP-9001 (rAAVrh74.MHCK7.micro-dystrophin)

SRP-9001 is an investigational gene transfer therapy intended to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. Sarepta is responsible for global development and manufacturing for SRP-9001 and plans to commercialize SRP-9001 in the United States upon receiving FDA approval. In December 2019, the Company announced a licensing agreement granting Roche the exclusive right to launch and commercialize SRP-9001 outside the United States. Sarepta has exclusive rights to the micro-dystrophin gene therapy program initially developed at the Abigail Wexner Research Institute at Nationwide Children’s Hospital.

About Sarepta

Sarepta Therapeutics, Inc., a biopharmaceutical company, is working to unlock the potential of RNA-based and gene therapy technologies to treat serious and life-threatening diseases like Duchenne muscular dystrophy (DMD). Sarepta’s primary focus is to advance new treatments for DMD rapidly.

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Pfizer doses the first participant with Its gene therapy

Pfizer doses the first participant in phase 3 study for Duchenne muscular dystrophy (DMD) investigational gene therapy.

Pfizer Inc. announced that the first participant has been dosed in the Phase 3 CIFFREO study, which will evaluate the efficacy and safety of investigational gene therapy candidate PF-06939926 in boys with Duchenne muscular dystrophy (DMD). The CIFFREO trial is expected to enroll 99 ambulatory male patients, ages 4 through 7, across 55 clinical trial sites in 15 countries. The first patient was dosed at a site in Barcelona, Spain, on December 29, 2020.

CIFFREO is a Phase 3 global, multicenter, randomized, double-blind, placebo-controlled study. The study’s primary endpoint is the change from baseline in the North Star Ambulatory Assessment (NSAA) at one year. The NSAA is a 17-item test that measures gross motor function in boys with DMD. Regardless of the cohort, eligible participants are scheduled to receive the investigational gene therapy, either at the start of the study or after one year following treatment with placebo. Participants will be followed in the CIFFREO study for five years after treatment with the investigational gene therapy. Trial participants will receive commercially representative drug products manufactured at Pfizer’s state-of-the-art gene therapy manufacturing facility in Sanford, North Carolina.

 

Brenda Cooperstone, MD, Chief Development Officer, Rare Disease, Pfizer Global Product Development  – “The initiation of our pivotal trial, which is the first Phase 3 DMD gene therapy program to begin enrolling eligible participants, is an important milestone for the community because there are currently no approved disease-modifying treatment options available for all genetic forms of DMD. We believe our gene therapy candidate, if successful in Phase 3 and approved, has the potential to significantly improve the trajectory of DMD disease progression, and we are working with worldwide regulatory authorities to initiate this program as quickly as possible in other countries.”

 

PF-06939926 received Fast Track designation from the U.S. Food and Drug Administration in October 2020 (read article), as well as Orphan Drug and Rare Pediatric Disease designations in the United States in May 2017.

 

Silvia Avila, President, Duchenne Parent Project Spain  – “DMD is a progressive disorder, and patients and parents are waiting desperately for treatment options. The initiation of this study is an important step forward for this community, and it fuels us with hope that one day there may be treatment options for boys impacted with this devastating disease.”

 

DMD is an X-linked disease caused by mutations in the gene encoding dystrophin, which is needed for muscle membrane stability. Due to the lack of dystrophin, boys present with muscle degeneration that progressively worsens with age to the extent that they require wheelchair assistance when they are in their early teens, and unfortunately, usually succumb to their disease by the time they are in their late twenties. It is estimated that there are ~140,000 boys affected by DMD worldwide.

 

About CIFFREO

CIFFREO is a Phase 3 global, multi-center, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of PF-06939926 investigational gene therapy in 99 ambulatory male participants, ages 4 through 7 years, with a genetic diagnosis of DMD who are on a stable daily regimen of glucocorticoids. The participants are negative for neutralizing antibodies against AAV9, as measured by the test done for the study as part of screening.

Eligible participants will be randomized into Cohort 1 or Cohort 2. Treatment will consist of two single intravenous infusions, one of PF-06939926 and one of placebo; approximately two thirds will be in Cohort 1 and receive PF-06939926 gene therapy at the start of the study and placebo after one year, and approximately one third will be in Cohort 2 and receive placebo at the start of the study and receive gene therapy after one year if they remain eligible. All participants will be followed in an open-label extension study for 5 years after treatment with the gene therapy. The study’s primary endpoint is a change from baseline at one year in the North Star Ambulatory Assessment (NSAA) total score. For more information, visit ciffreoduchennetrial.com.

 

About PF-06939926

PF-06939926 is an investigational recombinant adeno-associated virus serotype 9 (rAAV9) capsid carrying a shortened version of the human dystrophin gene (mini-dystrophin) under the control of a human muscle specific promotor. The rAAV9 capsid was chosen as the delivery vector because of its potential to target muscle tissue.

 

About Pfizer Rare Disease

Rare disease includes some of the most serious of all illnesses and impacts millions of patients worldwide, representing an opportunity to apply their knowledge and expertise to help make a significant impact on addressing unmet medical needs. The Pfizer focus on rare diseases builds on more than two decades of experience, a dedicated research unit focusing on rare disease, and a global portfolio of multiple medicines within several disease areas of focus, including rare hematologic, neurologic, cardiac and inherited metabolic disorders.

Pfizer Rare Disease combines pioneering science and a deep understanding of how diseases work with insights from innovative strategic collaborations with academic researchers, patients, and other companies to deliver transformative treatments and solutions. Pfizer innovates every day, leveraging its global footprint to accelerate the development and delivery of groundbreaking medicines and the hope of cures.

Click here to learn more about their Rare Disease portfolio and how Pfizer empowers patients, engage communities in their clinical development programs, and support programs that heighten disease awareness.

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Pfizer receives FDA fast track designation for DMD gene therapy

Pfizer receives FDA fast track designation for Duchenne muscular dystrophy (DMD) investigational gene therapy.

Official press release > NEW YORK–(BUSINESS WIRE)

Pfizer Inc. announced that its investigational gene therapy candidate (PF-06939926) being developed to treat Duchenne muscular dystrophy (DMD) received Fast Track designation from the U.S. Food and Drug Administration (FDA). PF-06939926 is currently being evaluated to determine the safety and efficacy of this gene therapy in boys with DMD.

Fast Track is a process designed to facilitate the development and expedite the review of new drugs that are intended to treat or prevent severe conditions that have the potential to address an unmet medical need. This designation was granted based on data from the Phase 1b study that indicated that the intravenous administration of PF-06939926 was well-tolerated during the infusion period, and dystrophin expression levels were sustained over 12 months.

 

Brenda Cooperstone, MD, Chief Development Officer, Rare Disease, Pfizer Global Product Development – “The FDA’s decision to grant our investigational gene therapy PF-06939926 Fast Track designation underscores the urgency to address a significant unmet treatment need for Duchenne muscular dystrophy. DMD is a devasting condition and patients, and their parents, are waiting desperately for treatment options. We are working to advance our planned Phase 3 program as quickly as possible.”

 

DMD is a devastating and life-threatening X-linked disease caused by mutations in the gene encoding dystrophin, which is needed for proper muscle membrane stability and function. Patients present with muscle degeneration that progressively worsens with age to the extent that they require wheelchair assistance when they are in their early teens, and unfortunately, usually succumb to their disease by the time they are in their late twenties. It is estimated that there are ~10-12,000 individuals affected with DMD in the U.S.

 

About PF-06939926

PF-06939926 is an investigational, recombinant adeno-associated virus serotype 9 (rAAV9) capsid carrying a shortened version of the human dystrophin gene (mini-dystrophin) under the control of a human muscle specific promotor. The rAAV9 capsid was chosen as the delivery vector because of its potential to target muscle tissue. Pfizer initiated the Phase 1b multi-center, open-label, non-randomized, ascending dose study of a single intravenous infusion of PF-06939926 in 2018. The goal of the study is to assess the safety and tolerability of this investigational gene therapy. Other objectives of the clinical study include measurement of dystrophin expression and distribution and assessments of muscle strength, quality and function.

Data from the Phase 1b DMD gene therapy program, including data from an additional nine boys, who were all administered the high dose of the investigational therapy. A total of 15 boys have now been treated with the high dose and 18 boys have been treated overall. > Sources<

  • No Serious Adverse Events (SAE) were observed among the nine additional boys who were treated using a modified immunomodulatory regimen and monitoring regimen. The prophylactic steroid treatment was also changed from 1 mg/kg to an intermediate dose of 2mg/kg.
  • Three of the nine boys were dosed with gene therapy product that was manufactured using the commercial manufacturing process developed at Pfizer’s facility in Sanford, North Carolina.
  • Based on these data, the Company plans to initiate the pivotal study in the next several weeks, with the plan to perform an interim analysis of the clinical data in 2022.

About Pfizer Rare Disease

Rare disease includes some of the most serious of all illnesses and impacts millions of patients worldwide, representing an opportunity to apply their knowledge and expertise to help make a significant impact on addressing unmet medical needs. The Pfizer focus on rare disease builds on more than two decades of experience, a dedicated research unit focusing on rare disease, and a global portfolio of multiple medicines within several disease areas of focus, including rare hematologic, neurologic, cardiac and inherited metabolic disorders.

Pfizer Rare Disease combines pioneering science and a deep understanding of how diseases work with insights from innovative strategic collaborations with academic researchers, patients, and other companies to deliver transformative treatments and solutions. Pfizer innovates every day, leveraging its global footprint to accelerate the development and delivery of groundbreaking medicines and the hope of cures.

Click here to learn more about their Rare Disease portfolio and how Pfizer empowers patients, engage communities in their clinical development programs, and support programs that heighten disease awareness.

Interesting links

La Force DMD talks with Dr. Jeffrey Chamberlain, a geneticist at the University of Washington, Seattle, about adenovirus-associated (AAV) micro-dystrophin gene replacement therapy.

La Force DMD / Press release from Pfizer about gene therapy

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Sustained functional improvement with micro-dystrophin gene treatment

Sarepta Therapeutics reports sustained functional improvement two years after treatment with SRP-9001, its investigational micro-dystrophin gene therapy for Duchenne muscular dystrophy.

  • Results demonstrate continued safety and tolerability of SRP-9001 in four participants with Duchenne.
  • All four participants demonstrated improvements in The North Star Ambulatory Assessment (NSAA)* scores than baseline and showed a durable response two years after the administration of SRP-9001.

Original press release > CAMBRIDGE, Mass., Sept. 28, 2020 (GLOBE NEWSWIRE)

Sarepta Therapeutics, Inc., announced two-year follow up results from four Duchenne muscular dystrophy (DMD) clinical trial participants who received SRP-9001. SRP-9001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of micro-dystrophin protein. Results presented at the 25th International Annual Congress of the World Muscle Society demonstrated that two years after a one-time infusion of SRP-9001, trial participants exhibited a mean 7.0 point improvement on the North Star Ambulatory Assessment (NSAA) compared to baseline.

 

Doug Ingram, President and CEO, Sarepta – “We continue to be encouraged by the safety profile and enduring treatment response that we have seen to date with SRP-9001 gene transfer therapy. The consistent results and functional improvements sustained over two years give us added confidence as we prepare for the results from Study 102, our randomized, double-blind, placebo-controlled study of SRP-9001. We continue to work with urgency to bring this potentially transformative treatment to patients as quickly as possible.”

 

In the open-label trial, known as Study 101, four ambulatory participants between the ages of 4 and 7 were treated with an infusion of SRP-9001. The therapy was well-tolerated in all participants over the two years. All adverse events were considered mild or moderate and occurred within 90 days of treatment. There were no serious adverse events or evidence of complement activation.

At day 90, all participants had confirmed vector transduction and showed functional improvement on the NSAA scale and reduced creatine kinase (CK) levels. Participants demonstrated a mean increase of 5.5 points from baseline one year after treatment and 7.0 points from baseline two years after treatment. The NSAA is a validated scale developed to measure functional motor abilities in ambulant children with Duchenne, with scores ranging from 0-34.

As previously disclosed, micro-dystrophin protein levels for participants in Study 101 were as follows: 12-weeks post-infusion, a mean of 81.2% muscle fibres expressing micro-dystrophin with a mean intensity at the sarcolemma by immunohistochemistry of 96% compared to normal biopsies. Adjusted for fat and fibrotic tissue, western blot showed a mean expression of 95.8%.

About SRP-9001

SRP-9001 is an investigational gene transfer therapy intended to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. Sarepta is responsible for global development and manufacturing for SRP-9001 and plans to commercialize SRP-9001 in the United States. In December 2019, the Company announced a licensing agreement granting Roche the exclusive right to launch and commercialize SRP-9001 outside the United States. Sarepta has exclusive rights to the micro-dystrophin gene therapy program initially developed at the Abigail Wexner Research Institute at Nationwide Children’s Hospital.

About Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a rare, fatal neuromuscular genetic disease in approximately one in every 3,500-5,000 males worldwide. DMD is caused by a change or mutation in the gene that encodes instructions for dystrophin. Symptoms of DMD usually appear in infants and toddlers. Affected children may experience developmental delays such as difficulty in walking, climbing stairs or standing from a sitting position. As the disease progresses, muscle weakness in the lower limbs spreads to the arms, neck and other areas. Most patients require full-time use of a wheelchair in their early teens and then progressively lose the ability to independently perform activities of daily living such as using the restroom, bathing and feeding. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and patients usually succumb to the disease in their twenties.

About Sarepta Therapeutics

Sarepta Therapeutics, Inc., a biopharmaceutical company, is working to unlock the potential of RNA-based and gene therapy technologies to treat severe and life-threatening diseases like Duchenne muscular dystrophy (DMD). Sarepta’s primary focus is to advance new therapies for DMD rapidly. Learn more here.

La Force DMD / Sarepta Therapeutics / Grounded in the DMD community.

The North Star Ambulatory Assessment (NSAA)

The North Star Ambulatory Assessment (NSAA) is a 17-item rating scale that is used to measure functional motor abilities in ambulant children with Duchenne Muscular Dystrophy (DMD). It is usually used to monitor the progression of the disease and treatment effects.

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Viltolarsen, exon 53 skipping therapy, approved

N.S. Pharma’s VILTEPSO™ (viltolarsen) injection now FDA-Approved in the U.S. for the treatment of Duchenne muscular dystrophy in patients amenable to exon 53 skipping therapy.

 

  • Patients taking VILTEPSO showed an increase in dystrophin expression to an average of 5.9% of normal after 20-24 weeks of treatment.
  • Overall, in a pivotal study of VILTEPSO, 100% of patients showed an increase in dystrophin levels after treatment, and 88% of patients showed dystrophin levels of 3% of average or higher.

Press release > PARAMUS, NJ: August 12, 2020 – N.S. Pharma, Inc.

 

N.S. Pharma announced that the U.S. Food & Drug Administration (FDA) has approved VILTEPSO™ (viltolarsen) injection for patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping therapy. VILTEPSO received an Accelerated Approval by the FDA based on an increase in dystrophin, an essential protein for supporting muscle health. Since a lack of dystrophin is the underlying cause of DMD, increasing dystrophin as much and as early as possible is a key goal in the treatment of DMD. VILTEPSO is the first and only exon 53 skipping therapy to demonstrate an increase in dystrophin in children as young as four years old. The continued approval of VILTEPSO may be contingent on confirmation of a clinical benefit in the Phase 3 confirmatory trial.

 

More about the study

The VILTEPSO New Drug Application (NDA) submission included results from a Phase 2, a two-period study in patients aged four to less than ten years of age conducted in North America (Study 1, N=16) and a multicenter, open-label study in boys five to less than 18 years of age conducted in Japan (Study 2, N=16).

In Study 1, of those patients who received the recommended dose of 80 mg/kg/wk (N=8), 100% of patients (8/8) showed an increase in dystrophin levels after treatment with VILTEPSO and 88% of patients (7/8) showed dystrophin levels of 3% or greater than normal. Overall, after 20-24 weeks of treatment, a mean increase in dystrophin expression to nearly 6% of normal was observed with VILTEPSO (80 mg/kg/wk) versus 0.6% at baseline. The most common side effects of VILTEPSO included upper respiratory tract infection, injection site reaction, cough and fever.

 

Vamshi Rao, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago – “For decades, neurologists who treat DMD have hoped for the discovery of therapies capable of significantly improving dystrophin production, and the magnitude of dystrophin increases observed with VILTEPSO are impressive. The approval of VILTEPSO is an exciting development for DMD patients amenable to exon 53 skipping therapy and may rapidly become a foundational treatment for these patients.”

 

  • In clinical studies, no patients experienced kidney toxicity during treatment with VILTEPSO. However, kidney toxicity from drugs like VILTEPSO may be possible. Your doctor may monitor the health of your kidneys before starting and during treatment with VILTEPSO.
  • The most common side effects of VILTEPSO included upper respiratory tract infection, injection site reaction, cough and fever.
  • For additional safety information, please see the full Prescribing Information.

N.S. Pharma continues to study the safety and efficacy of VILTEPSO in the confirmatory Phase 3 RACER53 trial. This study was initiated in October 2019 and is currently enrolling. The purpose of this Phase 3 trial is to confirm the clinical findings that were submitted under the Accelerated Approval pathway.

 

About VILTEPSO™ (viltolarsen) injection

Before its approval in the U.S., VILTEPSO was granted Priority Review as well as Rare Pediatric Disease, Orphan Drug and Fast Track Designations. In March 2020, VILTEPSO was approved in Japan for the treatment of patients with DMD who are amenable to exon 53 skipping therapy. Before its approval in Japan, VILTEPSO was granted the SAKIGAKE designation, Orphan Drug designation, and designation of Conditional Early Approval System.

VILTEPSO is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. This indication is approved under Accelerated Approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VILTEPSO. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. It is an infusion that doctors administer into the bloodstream.

 

How Viltolarsen works

Viltolarsen contains an artificial piece of mRNA that masks exon 53, causing cells to “skip” this exon when they are making mature mRNA. This skip restores the so-called “reading frame” of the mRNA molecule. In other words, it ensures that the remaining exons fit together again, allowing a cell’s protein-making machinery to synthesize a shorter but working dystrophin protein.

Because viltolarsen is specific to exon 53, the treatment is effective only in those DMD patients who have a mutation that is amenable to exon 53 skipping. Thanks to Muscular Dystrophy News Today for this description.

 

N.S. Pharma

NS Pharma, Inc. is a wholly-owned subsidiary of Nippon Shinyaku Co., Ltd. For more information, please visit www.nspharma.com. N.S. Pharma is a registered trademark of the Nippon Shinyaku group of companies.

N.S. Pharma will provide families, physicians and healthcare professionals dedicated and individualized resources every step of the way through the N.S. Support program. N.S. Pharma will be hosting a series of webinars on the comprehensive care coordination available through N.S. Support. Follow them on LinkedIn and Twitter for information and registration for upcoming webinars.

 

Tsugio Tanaka, President, NS Pharma, Inc. – “On behalf of NS Pharma and Nippon Shinyaku, I would like to express our deepest gratitude to the families and physicians who participated in our clinical trials and made today’s approval possible. We are proud to now offer an important new treatment option to help address the significant unmet needs caused by this devastating disease.”

 

More about DMD

DMD is caused by genetic mutations that prevent dystrophin production. Patients with DMD experience progressive and irreversible muscle loss with symptoms appearing as early as two years of age. 

Duchenne muscular dystrophy occurs primarily in males. Early signs of DMD may include delayed ability to sit, stand or walk. There is a progressive loss of mobility, and by adolescence, patients with DMD may require the use of a wheelchair. Cardiac and respiratory muscle problems begin in the teenage years and lead to serious, life-threatening complications. Read more here.

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Sarepta is seeking the approval of casimersen for DMD patients

Sarepta Therapeutics Completes Submission of New Drug Application Seeking Approval of Casimersen (SRP-4045) for Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 45

  • Casimersen is designed for the treatment of exon 45 amenable patients, approximately eight percent of patients with Duchenne
  • Casimersen is the third exon-skipping medicine using the Company’s proprietary PMO RNA-based platform. 

 

CAMBRIDGE, Mass., June 26, 2020 (GLOBE NEWSWIRE) >Original press release here

Sarepta Therapeutics, Inc. has completed the submission of a rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for casimersen (SRP-4045). Casimersen, a phosphorodiamidate morpholino oligomer (PMO), is engineered to treat patients with Duchenne muscular dystrophy (DMD) who have genetic mutations that are amenable to skipping exon 45 of the Duchenne gene.

The completion of the rolling submission includes data from the casimersen arm of the ESSENCE study (also known as study 4045-301), a global, randomized, double-blind, placebo-controlled Phase 3 study evaluating efficacy and safety in patients amenable to skipping exons 45 and 53. An interim analysis from ESSENCE demonstrated a statistically significant increase in dystrophin production as measured by western blot* in patients who received casimersen compared to baseline and placebo. The study is ongoing and remains blinded to collect additional efficacy and safety data. If the casimersen NDA is accepted and granted accelerated approval, the completed ESSENCE study will serve as a post-marketing confirmatory study.

 

Doug Ingram, president and chief executive officer, Sarepta Therapeutics. – “The completion of our casimersen submission is an important milestone in our journey to advance treatments for the greatest possible number of people living with Duchenne muscular dystrophy. If approved, casimersen will be our third approved therapy for sub-populations of Duchenne. Together with our other approved therapies, we have the potential to treat nearly 30% of Duchenne patients in the United States. Our proprietary PMO platform is an important focus of our pipeline, and we owe our clinical progress to the patients and families participating in our studies.”

 

About Casimersen

Casimersen uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 45 of the DMD gene. Casimersen is designed to bind to exon 45 of dystrophin pre-mRNA, resulting in exclusion, or “skipping,” of this exon during mRNA* processing in patients with genetic mutations that are amenable to exon 45 skipping. Exon skipping is intended to allow the production of an internally truncated dystrophin protein.

What about Canada?

At this moment, casimersen is not available in Canada. We hope that shortly, Sarepta Therapeutics will file a request for marketing approval with Health Canada.

For a better understanding

  • * The western blot is a widely used analytical technique in molecular biology, immunogenetics and other molecular biology disciplines to detect specific proteins in a sample of tissue homogenate or extract.
  • * Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and DNA are nucleic acids and, along with lipids, proteins and carbohydrates, constitute the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA, it is more often found in nature as a single-strand folded onto itself, rather than a paired double-strand.
  • Read more here
  • Grounded in the DMD community

About DMD

Duchenne muscular dystrophy (DMD) is a disease that almost exclusively affects boys and whose incidence is 1 in 3,500. It is sporadic that Duchenne muscular dystrophy (DMD) will affect girls. Those affected are usually diagnosed around the age of five, but symptoms may be visible from early childhood. It is a degenerative disease of the muscles caused by a genetic mutation. The Duchenne muscular dystrophy (DMD) – for which no treatment is currently available – directly affects skeletal muscles. Without treatment, the consequences of the disease are dire for those afflicted and their families.

About Sarepta Therapeutics

The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Company’s programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visit www.sarepta.com or follow them on TwitterLinkedInInstagram and Facebook.