dmd gene therapy cost

Rasmussen M, Risberg K, Vollo A, Skjeldal OH. This restriction was imposed because all things being equal, contemporary evidence is of much greater relevance than historic evidence. There are important evidence gaps, particularly in measuring prevalence and mortality, although people seem to be living longer with the condition, which may be partially as a result of more widespread prescribing of corticosteroids, improved access to ventilation and development and publication of more specific and thorough care guidelines. CRISPR Correction of Duchenne Muscular Dystrophy - PMC Details are reported in Additional file 2: Appendix 2. Nance explains that DMD is caused by deletions, duplications, point mutations or premature stop codons in the gene that makes dystrophin, a protein that stabilizes muscle cell membranes and supports the contractile apparatus. 2015;262(3):62941. The FDA remains committed to facilitating the development of innovative new therapies to reduce the impact of debilitating diseases and to improve outcomes and quality of life for those affected.. Credit: Mehau Kulyk/Science Photo Library. 2015;36(4):395402. $1,432. Abstract Neuromuscular disorders encompass a heterogeneous group of conditions that impair the function of muscles, motor neurons, peripheral nerves, and neuromuscular junctions. It is not clear why this should be the case, although it should be noted that the German study was of better quality and was published more recently. BioMarin paid KSR for the costs of preparing the publication however KSR retained editorial control. It is usually observed between the ages of three and six. CAS 2013;5. https://www.ncbi.nlm.nih.gov/pubmed/23867975. Point prevalence of DMD was 10.2 per 100,000 males aged 524 in 2010. McDonald CM, McDonald DA, Bagley A, Sienko Thomas S, Buckon CE, Henricson E, Nicorici A, Sussman MD. Promising gene therapy for Duchenne muscular dystrophy - UC Davis Health Expensive treatments for genetic disorders are arriving. Results are set out in Table3 with changes in 6MWD in Table4. The single treatment will cost US$2.8 million, making it the most expensive medicine in history. Two studies reported the distribution of general severity i.e. Quality of study reporting was assessed in Additional file 4: Appendix 4 (Table A3). Diagnosis method was also shown to be related to survival with molecular testing associated with a higher mortality than clinical only [19]. Eur J Hum Genet. ELEVIDYS, an adeno-associated virus-based gene therapy, is approved for the treatment of ambulatory pediatric patients aged four through five years with Duchenne muscular dystrophy (DMD) with a . The most frequently used tool for measuring HRQoL was the PedsQL which was used in five studies [21, 23, 50, 52, 53] and, for utilities, HUI was calculated for Germany,Italy, UK and US populations in Landfeldt [58]. 2013;44(02):FV16_03. Furthermore, . SOURCE: ICER. However, US funding mechanisms explain the relative high cost of insurance premiums. Recent progress has greatly increased the prospects for successful gene therapy of DMD, and here we summarize the most promising developments. We have reviewed contemporary evidence of burden, epidemiology, illness costs and treatment patterns of DMD. But these conversations are starting to change because of the hope that new therapies may provide. Pediatr Pulmonol. . Passamano L, Taglia A, Palladino A, Viggiano E, DAmbrosio P, Scutifero M, Rosaria Cecio M, Torre V, DE Luca F, Picillo E, Paciello O, Piluso G, Nigro G, Politano L. Improvement of survival in Duchenne muscular dystrophy: retrospective analysis of 835 patients. Duchenne muscular dystrophy is a rare and serious genetic condition which worsens over time, leading to weakness and wasting away of the bodys muscles. Duchenne muscular dystrophy (DMD) is an X-linked, muscle wasting disease that affects 1 in 5000 males. Sarepta Therapeutics: 'Hold' Amid Market Myopia (NASDAQ:SRPT) Selsby JT. PLoS Curr. Birth prevalence ranged from 15.9 to 19.5 per 100,000 live births. (DOC 1545 kb), Summary of included studies by research question [64,65,66,67,68,69,70,71,72,73]. Access Nature and 54 other Nature Portfolio journals, Get Nature+, our best-value online-access subscription, Receive 12 print issues and online access, Prices may be subject to local taxes which are calculated during checkout, doi: https://doi.org/10.1038/d41573-023-00103-y. This raises the risk of side effects, including organ damage. Growth and psychomotor development of patients with Duchenne muscular dystrophy. Both Rall [19] and Kieny [20] were found to be of medium quality but neither provided an adequate description of study participants. The remaining three studies were judged to be of low quality [14,15,16]. 2013;56(6):44354. The decision date was delayed late in May after FDA officials and advisers raised concerns about the strength of Sareptas data so far; SRP-9001 seems to have only a modest effect on muscle function, and only in some people. Kota P, Aleksandrov AA, Riordan JR, Dokholyan NV. There was international variation in use of corticosteroids, scoliosis surgery, ventilation and physiotherapy. Orphanet J Rare Dis 12, 79 (2017). PubMed Central Individualized Care Through Translocation Testing, Innovations in Care for Patients with Pediatric Epilepsy, Developing Implantable and Wearable Technology to Treat Spinal Cord Injury. However this study was judged of low quality reporting according to STROBE criteria, largely because of uncertainty surrounding representativeness of those evaluated. 2011;12:37. Results are set out in Additional file 4: Appendix 4 Table A11. York: University of York; 2009. accessed 23.3.11. 2014;261(7):126988. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. All studies provided at least the total score and two studies, by Schreiber-Katz [23] and Uzark [52] compared the DMD individual value with one elicited from the parent as proxy. And I think the evidence is murky," Alexander says. Most inter-country variation in large spend categories was found for physio/OT where spend in the US was 4.5 times that in Italy, psychology where spend in the US was 14.4 times that in either Italy or Germany, specialist physicians where spend in the US was 21.9 times that in Italy and visits to healthcare professionals where spend in the US was seven times that in Italy. Uptake of scoliosis surgery was reported in one French study reporting that 52% of DMD patients underwent this surgery between 2001 and 2011 (Khirani [35]). These showed that the boys muscles made microdystrophin, but the children had no statistically significant improvement in muscle function one year after the drug was administered. Today, the U.S. Food and Drug Administration approved Elevidys, the first gene therapy for the treatment of pediatric patients 4 through 5 years of age with Duchenne muscular dystrophy. Although the numbers of cases were fairly low, only 27.9% of patients born prior to 1970 underwent tracheostomy, whereas this proportion had risen to 47.8% for patients born after 1980 (an even higher percentage was recorded for patients born between 1970 and 1980 at 58.5%). This is attributed to the widespread prescribing of corticosteroids, improved access to ventilation and the publication of more thorough and specific guidelines of care. Duchenne muscular dystrophy gene therapy in the canine model. There are more than 30 types of muscular dystrophies, each affecting specific muscle groups and showing symptoms at different ages. A drug approved this way to prevent premature birth was recently withdrawn after being found useless. Also more recent studies should have a better diagnosis procedure, distinguish better between BMD and DMD and be more representative of the DMD population. The FDA granted approval based on an evaluation of data submitted by the sponsor. ISSN 1474-1784 (online) In Q1 2023, Sarepta Therapeutics reported a GAAP net loss of $516.8 million, significantly up from a $105 million loss in Q1 2022 due to a debt . Additionally, myocarditis (inflammation of heart muscle) and elevations of troponin-I (a heart protein found in the blood after heart muscle injury) have been observed following use of Elevidys in clinical trials. In 2010, recommendations were made to consider glucocorticoids, including Deflazacort and Prednisone, as first line therapies for DMD patients of 2 years and over whose condition was not improving (Bushby [6]). Google Scholar. PLoS Curr. The one-time treatment, named Elevidys, will cost US$3.2 million, according to Sarepta, the Cambridge, Massachusetts-based company that developed it. Spurney C, Shimizu R, Morgenroth LP, Kolski H, Gordish-Dressman H, Clemens PR, Investigators C. Cooperative International Neuromuscular Research Group Duchenne Natural History Study demonstrates insufficient diagnosis and treatment of cardiomyopathy in Duchenne muscular dystrophy. Population characteristics in earlier studies may therefore be different to those completed more recently. Others are searching for ways to improve the viral vector that carries the gene. We found no evidence on the impact of specific mutations on severity/disease progression. The joint Center for Life Sciences (CLS) at Tsinghua and Peking universities invites application for its International Fellow program. Orphanet Journal of Rare Diseases 2012;101(4):42432. Henricson E, Abresch R, Han JJ, Nicorici A, Goude Keller E, Elfring G, Reha A, Barth J, McDonald CM. Study reporting quality (STROBE) and characteristics. Its still unclear how long the therapys effect will last, although Sareptas data from four children suggest that the clinical improvements can persist four years after treatment. Health Qual Life Outcomes. Gene Therapy for Duchenne Muscular Dystrophy. PLoS Curr. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease for these children, and the urgent unmet medical need. Muscular dystrophy patients get first gene therapy - NPR Fifty-eight studies were reviewed for reporting quality with three assessed as high quality, 33 as medium quality and 22 low quality. NA, TB, MW, RL and SR were responsible for acquisition, analysis and interpretation of data. Most current treatment approaches address the symptoms of the disease, but not its underlying genetic cause. A recent systematic review of cost of illness evidence in rare diseases (Angelis [63]) also failed to identify any contemporary cost of illness studies for DMD, which gives us some confidence that most relevant studies have been identified in our review. Davidson ZE, Ryan MM, Kornberg AJ, Sinclair K, Cairns A, Walker KZ, Truby H. Observations of body mass index in Duchenne muscular dystrophy: a longitudinal study. There was a far higher percentage of the German population [23] in the most severe equivalent category i.e. In the meantime, to ensure continued support, we are displaying the site without styles Ann Neurol. Cardiac function or percentage with cardiomyopathy was reported in six studies. 2015;30(1):216. Nature Reviews Drug Discovery (Nat Rev Drug Discov) Most people with the disease die in their 30s or 40s. Current guidelines were also scrutinised for the latest treatment recommendations. Official answer by Drugs.com The new drugs approved by the FDA for the treatment of Duchenne muscular dystrophy (DMD) are: Amondys 45 (casimersen) Viltepso (viltolarsen) Vyondys 53 (golodirsen) For example, a French study [17] found that median survival for those born between 1970 and 1994 was 40.95years compared to a mean lifespan of 25.77years for those born between 1955 and 1969. PDF SmartPA Criteria Proposal - Missouri Department of Social Services The percentage of the DMD population with scoliosis varied between 3.9% in a Japanese study of males with no age restrictions (Nakamura [26]) and 52.1% in a French study of boys ranging between 6 and 19years old (Khirani [35]). DMD can be suspected when a male child shows abnormal muscle function and hypertrophy but tends to be confirmed following additional clinical presentation (including distribution of weakness) and a complete medical and family history. For example there is evidence to suggest that the generic PedsQL does not correlate well with progression of disease in DMD [60]. Mah [15] failed to adequately describe the eligibility criteria, outcomes or study participants. Elevated levels of serum creatine kinase support further diagnostic work-up for DMD. I do think the notion of regulatory flexibility can get bent out of shape, Alexander says. Other important sources include ongoing natural history studies run by The Cooperative International Neuromuscular Research Group (CINRG). PLoS One. Affected individuals become wheelchair bound by the age of twelve and eventually die in their third decade due to respiratory and cardiac complications. PLoS One. Three of these studies began with those that were ambulant, two that followed up for 3 years in Italy by Pane [34] and in Italy and Belgium by Pane [42] and one that followed up for 7 years in the UK by Ricotti [43]. Let's first review earnings. Further subdivision of direct costs was provided including a detailed breakdown according to service headings (as opposed to staff group headings). But there's an intense debate about this. The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review, https://doi.org/10.1186/s13023-017-0631-3, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542198/, https://www.ncbi.nlm.nih.gov/pubmed/23867975, 10.1371/annotation/cbe611fe-cda9-4d98-9574-0ac18e109daa, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269886/, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/. The data that support the findings of this study are available from KSR Ltd, UK but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. In DMD patients and in the corresponding pig model with a deletion of DMD exon 52 (DMDD52), expression of an internally shortened dystrophin can be achieved by skipping of DMD exon 51 to reframe . This information was provided by three people with knowledge of the FDA deliberations. The FDA concluded that the data submitted by the applicant demonstrated that an increase in this surrogate endpoint (expression of Elevidys micro-dystrophin) is reasonably likely to predict clinical benefit in individuals 4 to 5 years of age with DMD who do not have significant pre-existing antibody titers against the AAV rh74 vector or have other contraindications based on the inclusion criteria of the clinical trials. Get the most important science stories of the day, free in your inbox. 2023 BioMed Central Ltd unless otherwise stated. Neuromuscular disorders in children in south-eastern Norway. We found forty one studies reporting aspects of disease severity and/or its progression. Kempen JC, Harlaar J, van der Kooi AJ, de Groot IJ, van den Bergen JC, Niks EH, Verschuuren JJ, Brehm MA. hide caption. You are using a browser version with limited support for CSS. From the figure presented, the number of patients per country in the national DMD registry can be estimated and the point prevalence calculated. We excluded any studies which only reported on mixed populations (e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269886/. The only international study had an estimate of 361.1m for those at least 5 years old (McDonald [22]). Called Zynteglo, the gene therapy is designed to treat beta-thalassemia, a rare disease with . Of the studies reporting point prevalence, a study by Bladen [16] reported on TREAT-NMD, a worldwide network for neuromuscular diseases which supports new therapies for patients . As the most As an integral part of the Chinese efforts to build first-rate universities, the Center for Life Sciences (CLS) was established in 2011 at Tsinghua State Key Laboratory of Primate Biomedical Research (LPBR) is a recognized institute for cutting-edge research on primate b State Key Laboratory of Primate Biomedical Research (Kunming University of Science and Technology), The University of Texas Southwestern Medical Center (UT Southwestern Medical Center). Lancet. Elevidys, a Gene Therapy for Duchenne Muscular Dystrophy, Gets FDA Approval 2011;36(15):E100917. 2013;48(1):3254. Scoliosis, which causes the spine to curve sideways and/or forward or backward, leads to additional orthopaedic problems as one shoulder or hip becomes higher than the other leading to potential respiratory problems as the chest cavity reduces. Patients given Elevidys may also be at risk for severe immune-mediated myositis (muscle inflammation). Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy. 2013;34(11):144957. Increased longevity means that studies of prevalence based only on younger populations will become less representative of the disease burden of DMD. Such studies offer the best potential to fully capture burden levels in an entire economy or location and ultimately to improve clinical awareness. Thus poor reporting makes it very difficult to assess possible changes in the way DMD has been defined over time. New masking guidelines Muscle Nerve. Of the 282 full papers that were screened, 221 did not meet the inclusion criteria and were excluded. This problem is exacerbated by inadequate descriptions of eligibility criteria and participants. Some of those who voted in favour of the therapy say that because DMD progresses slowly, it might be difficult to determine the drugs effect after just one year. Duchenne muscular dystrophy is the most common inherited neuromuscular disorder among children. But Carsten Bnnemann, a neurologist at the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, who co-led the study, says that gene therapies will eventually have to be tailored to help these patients. This committee narrowly recommended the approval by eight votes to six. Prevalence of fatigue, pain, and affective disorders in adults with Duchenne muscular dystrophy and their associations with quality of life. included Becker Muscular Dystrophy (BMD) or other forms of non-Duchenne Muscular Dystrophy). Fifty-eight studies (from 61 papers) were therefore included in the review. In an eagerly anticipated decision, the Food and Drug Administration Thursday approved the first gene therapy for muscular dystrophy. Gene Therapy for Duchenne muscular dystrophy - PubMed From a statistical standpoint, [Sarepta] havent pled their case, he says. Pictured: A conceptual illustration of a DNA helix. FDA Duchenne muscular dystrophy gene therapy : Shots - NPR Results are set out in Table5. Clinical researchers at UC Davis Health are using a gene therapy approach for Duchenne muscular dystrophy (DMD), the rare genetic disease that mainly occurs in boys and causes a steady loss of muscle and premature death. Genotype and phenotype characterization in a large dystrophinopathic cohort with extended follow-up. The costs of social care are also 5.4 times higher. However, it is also interesting to speculate that lack of change in self-reported quality of life with stage that was observed in two studies is not related to insensitivity of instrument, but reflects the stability irrespective of deterioration in physical status [55, 57]. Information on co-payments was also provided as part of the Landfeldt [58] study. We identified three studies reporting information on the survival of DMD patients [17,18,19]. Rall S, Grimm T. Survival in Duchenne muscular dystrophy. The relationship with age was shown clearly in a US study by Mayer [27] in that there was no loss of ambulation before age 8 years and progressive loss until age 1618 years, after which loss was 100%. Lim Y, Velozo C, Bendixen RM. 2014;9:210. The respiratory management of patients with Duchenne muscular dystrophy: a DMD care considerations working group specialty article. To obtain The Landfeldt [58] study provided inter-country comparisons of indirect costs. This is could have a number of implications, one being that the improvement in survival in those patients with true DMD, at least according to molecular testing, will never be known. Parent proxy scores, where collated, were similar to directly elicited values. Gene therapy challenge: How much should it cost and how do we pay for For difficult epilepsy cases, Johns Hopkins experts use the latest, less invasive diagnostic and treatment tools. 2014;24(6):48291. The average Part D plan deductible in 2022 is $367.80 per year. One French study (Martigne [28]) reported a mean age of ambulation loss of 10years. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. TREAT-NMD Neuromuscular Network. Most boys end up in wheelchairs before they become teenagers. 2010;25(9):113044. Epidemiology and burden of disease outcomes of interest were: point prevalence, birth prevalence, demographic characteristics, clinical characteristics of the disease, mortality, incidence/prevalence of comorbidities and progression of the disease. All three studies (one each from Italy, France and Germany) reported median survival between 24 and 26years. Romitti [14] did not report an adequate description of the study design, nor did it fully describe the eligibility criteria or study participants. Per capita cost burden increases with disease progression. The point prevalence of DMD was 16.2 per 100,000 males under 18years of age in this region reported on 1st July 2005. But regulatory documents show that agency reviewers were divided on the case for the therapys efficacy. J Neurol. Muscle Nerve. The 6 minute walk test and performance of upper limb in ambulant Duchenne muscular dystrophy boys. 2010;45(8):73948. As mentioned above, the average premium for Medicare Part D plans in 2022 is $47.59 per month. "You'd like to see approval for as broad a range of patients as possible. The costs of informal care time were 5.4 times higher for stage 5 patients than for stage 1. Additionally, email alerts and RSS feeds were set up to ensure the latest research was not missed. PubMed Duchenne causes the muscles in the body to become weak and damaged over time and is eventually fatal. Countries of interest included those in European Union (EU), South America, North America, Japan and Turkey (following advice from content experts at BioMarin Pharmaceuticals). Frontiers | Adeno-Associated Virus (AAV)-Mediated Gene Therapy for Quality of study reporting was assessed in Additional file 4: Appendix 4 (Table A1 and Table A2). That means allowing the disease to progress, and potentially stabilizing it only after boys have lost more muscle function. The study by Pane [34] found that, over 3 years, the percentage loss of ambulation in those who were originally ambulant varied from 5.2% for those who could originally walk at least 350m (<7years old) to 64% for those who could originally walk less than 350m (7years old).
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