Category Archives: Gene therapy

The U.S. Food and Drug Administration has given the green light for the first gene therapy that treats a rare form of muscular dystrophy to be used in most people who have the disease and a certain genetic mutation.Related video above: Major drug companies cap asthma medication costsLast year, the drug Elevidys, from the biotech company Sarepta Therapeutics was approved to treat only children ages 4 and 5 with Duchenne muscular dystrophy, one of the most severe forms of inherited muscular dystrophies, who have a confirmed mutation in a gene called DMD that is associated with muscle strength.The FDA announced Thursday that it had given traditional approval for Elevidys for ambulatory people 4 and older with a confirmed mutation in the DMD gene and accelerated approval for non-ambulatory people 4 and older with this mutation. Theres not enough data on safety to support its use in children under 4, the agency says.Elevidys, given as a one-time intravenous infusion, costs about $3.2 million per patient, making it among the most expensive drugs in the world. Although eye-popping, such a price tag isnt out of step with other one-time gene therapies, which have topped $3 million to 4 million per patient in recent years.Elevidys was previously approved under the FDAs accelerated approval pathway, which clears medicines for diseases where theyre urgently needed based on data suggesting that theyre likely to confer clinical benefits. The drug has been closely monitored since that approval, and in October, Sarepta Therapeutics released results from a confirmatory trial showing that the therapy missed its primary goal a measure of how well kids can move but was successful on a number of secondary measures.The approval addressed an urgent unmet medical need and is an important advancement in the treatment of Duchenne muscular dystrophy, a devastating condition with limited treatment options, that leads to a progressive deterioration of an individuals health over time, Dr. Peter Marks, the director of the FDAs Center for Biologics Evaluation and Research, said in a news release at the time.It was the first time a therapy of this nature a one-time treatment that delivers a working copy of a gene to make up for one that leads to disease had been cleared under the accelerated approval framework. The move came after emotional testimonials from families at an FDA advisory committee meeting.Duchenne muscular dystrophy causes progressive muscle weakness that can rob children of their ability to walk by the time theyre teenagers, and many dont live well into their 30s. It primarily affects boys because of the way its inherited, affecting an estimated 1 in 3,300 boys.The Muscular Dystrophy Association trusts the decision of the FDA, which weighs the risks and benefits of the drug, said Dr. Sharon Hesterlee, chief researcher at the association.Ultimately, what we want is whats best for our patient community and thats balancing that risk-benefit ratio appropriately, she said.Potential risks of Elevidys include increases in certain liver enzyme levels and acute serious liver injury. The most common side effects of the drug include vomiting, nausea, increased liver function tests and fever.Yet a major benefit is that the gene therapy provides another option for people with Duchenne muscular dystrophy, and its administered just once.There is no cure for Duchenne muscular dystrophy, and outside of Elevidys, treatments are limited. Other approaches may include steroid medications, certain drugs that change how the muscle cells read the mutated gene, physical therapy or surgery to correct spinal curvature, Hesterlee said.Right now, the main standard of care for Duchenne is corticosteroids, like prednisone, although there are some newer drugs available. These kids are still often on chronic doses of steroids for many, many years, she said, adding that the side effects of corticosteroids such as weight gain, behavioral issues and increased risk of bone breakage are not ideal.Duchenne muscular dystrophy can be difficult to treat, she said, and having more treatment options that are proven to be effective remains important.Muscle makes up a significant amount of your body mass. So when you have a disease like this, its really impacting a lot of tissue. So anything you do, youre looking at trying to bring back or stop a disease process thats really throughout the body, and its a disease thats progressive, so you lose more and more muscle over time, Hesterlee said.Thats made it pretty challenging, but weve certainly learned a lot, she said. You cant overlook the fact that these boys are living so much longer and doing so much better. Even 20 years ago, they were dying in their teens, and many of them are now living into their 30s. Theyre going to college; they have girlfriends; some of them have gotten married. These are things that werent happening years ago. So weve made a tremendous amount of progress.

The U.S. Food and Drug Administration has given the green light for the first gene therapy that treats a rare form of muscular dystrophy to be used in most people who have the disease and a certain genetic mutation.

Related video above: Major drug companies cap asthma medication costs

Last year, the drug Elevidys, from the biotech company Sarepta Therapeutics was approved to treat only children ages 4 and 5 with Duchenne muscular dystrophy, one of the most severe forms of inherited muscular dystrophies, who have a confirmed mutation in a gene called DMD that is associated with muscle strength.

The FDA announced Thursday that it had given traditional approval for Elevidys for ambulatory people 4 and older with a confirmed mutation in the DMD gene and accelerated approval for non-ambulatory people 4 and older with this mutation. Theres not enough data on safety to support its use in children under 4, the agency says.

Elevidys, given as a one-time intravenous infusion, costs about $3.2 million per patient, making it among the most expensive drugs in the world. Although eye-popping, such a price tag isnt out of step with other one-time gene therapies, which have topped $3 million to 4 million per patient in recent years.

Elevidys was previously approved under the FDAs accelerated approval pathway, which clears medicines for diseases where theyre urgently needed based on data suggesting that theyre likely to confer clinical benefits. The drug has been closely monitored since that approval, and in October, Sarepta Therapeutics released results from a confirmatory trial showing that the therapy missed its primary goal a measure of how well kids can move but was successful on a number of secondary measures.

The approval addressed an urgent unmet medical need and is an important advancement in the treatment of Duchenne muscular dystrophy, a devastating condition with limited treatment options, that leads to a progressive deterioration of an individuals health over time, Dr. Peter Marks, the director of the FDAs Center for Biologics Evaluation and Research, said in a news release at the time.

It was the first time a therapy of this nature a one-time treatment that delivers a working copy of a gene to make up for one that leads to disease had been cleared under the accelerated approval framework. The move came after emotional testimonials from families at an FDA advisory committee meeting.

Duchenne muscular dystrophy causes progressive muscle weakness that can rob children of their ability to walk by the time theyre teenagers, and many dont live well into their 30s. It primarily affects boys because of the way its inherited, affecting an estimated 1 in 3,300 boys.

The Muscular Dystrophy Association trusts the decision of the FDA, which weighs the risks and benefits of the drug, said Dr. Sharon Hesterlee, chief researcher at the association.

Ultimately, what we want is whats best for our patient community and thats balancing that risk-benefit ratio appropriately, she said.

Potential risks of Elevidys include increases in certain liver enzyme levels and acute serious liver injury. The most common side effects of the drug include vomiting, nausea, increased liver function tests and fever.

Yet a major benefit is that the gene therapy provides another option for people with Duchenne muscular dystrophy, and its administered just once.

There is no cure for Duchenne muscular dystrophy, and outside of Elevidys, treatments are limited. Other approaches may include steroid medications, certain drugs that change how the muscle cells read the mutated gene, physical therapy or surgery to correct spinal curvature, Hesterlee said.

Right now, the main standard of care for Duchenne is corticosteroids, like prednisone, although there are some newer drugs available. These kids are still often on chronic doses of steroids for many, many years, she said, adding that the side effects of corticosteroids such as weight gain, behavioral issues and increased risk of bone breakage are not ideal.

Duchenne muscular dystrophy can be difficult to treat, she said, and having more treatment options that are proven to be effective remains important.

Muscle makes up a significant amount of your body mass. So when you have a disease like this, its really impacting a lot of tissue. So anything you do, youre looking at trying to bring back or stop a disease process thats really throughout the body, and its a disease thats progressive, so you lose more and more muscle over time, Hesterlee said.

Thats made it pretty challenging, but weve certainly learned a lot, she said. You cant overlook the fact that these boys are living so much longer and doing so much better. Even 20 years ago, they were dying in their teens, and many of them are now living into their 30s. Theyre going to college; they have girlfriends; some of them have gotten married. These are things that werent happening years ago. So weve made a tremendous amount of progress.

Continued here:
FDA expands approval of first gene therapy for rare form of muscular dystrophy - WYFF4 Greenville

Marks, P. & Witten, C. Toward a new framework for the development of individualized therapies. Gene Ther. 28, 615617 (2021).

Article CAS PubMed Google Scholar

Kulkarni, J. A. et al. The current landscape of nucleic acid therapeutics. Nat. Nanotechnol. 16, 630643 (2021). This landmark review article comprehensively summarizes biological and technological advancements in four major platforms that accelerated the clinical utility of nucleic acid therapeutics.

Article CAS PubMed Google Scholar

Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M. & Sah, D. W. Y. Gene therapy for neurological disorders: progress and prospects. Nat. Rev. Drug. Discov. 17, 641659 (2018).

Article CAS PubMed Google Scholar

Bulaklak, K. & Gersbach, C. A. The once and future gene therapy. Nat. Commun. 11, 5820 (2020).

Article CAS PubMed PubMed Central Google Scholar

Nance, E., Pun, S. H., Saigal, R. & Sellers, D. L. Drug delivery to the central nervous system. Nat. Rev. Mater. 7, 314331 (2022).

Article CAS PubMed Google Scholar

Ling, Q., Herstine, J. A., Bradbury, A. & Gray, S. J. AAV-based in vivo gene therapy for neurological disorders. Nat. Rev. Drug. Discov. 22, 789806 (2023).

Article CAS PubMed Google Scholar

Terstappen, G. C., Meyer, A. H., Bell, R. D. & Zhang, W. Strategies for delivering therapeutics across the bloodbrain barrier. Nat. Rev. Drug. Discov. 20, 362383 (2021).

Article CAS PubMed Google Scholar

van Haasteren, J., Li, J., Scheideler, O. J., Murthy, N. & Schaffer, D. V. The delivery challenge: fulfilling the promise of therapeutic genome editing. Nat. Biotechnol. 38, 845855 (2020).

Article PubMed Google Scholar

Yin, H. et al. Non-viral vectors for gene-based therapy. Nat. Rev. Genet. 15, 541555 (2014).

Article CAS PubMed Google Scholar

Nbrega, C., Mendona, L. & Matos, C. A. in A Handbook of Gene and Cell Therapy (eds Nbrega, C., Mendona, L. & Matos, C. A.) 117126 (Springer International, 2020).

Lunn, M. R. & Wang, C. H. Spinal muscular atrophy. Lancet 371, 21202133 (2008).

Article PubMed Google Scholar

Mendell, J. R. et al. Five-year extension results of the phase 1 START trial of onasemnogene abeparvovec in spinal muscular atrophy. JAMA Neurol. 78, 834841 (2021). This key paper presents the findings of a clinical trial of Zolgensma a one-time-only gene therapy product used to treat monogenic SMA in paediatric patients.

Article PubMed Google Scholar

Mendell, J. R. et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 377, 17131722 (2017).

Article CAS PubMed Google Scholar

Eichler, F. et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N. Engl. J. Med. 377, 16301638 (2017).

Article CAS PubMed PubMed Central Google Scholar

Keam, S. J. Eladocagene exuparvovec: first approval. Drugs 82, 14271432 (2022).

CAS PubMed Google Scholar

Rafii, M. S. et al. A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimers disease. Alzheimers Dement. 10, 571581 (2014).

Article PubMed Google Scholar

US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT00876863 (2020).

Klein, C. & Schlossmacher, M. G. The genetics of Parkinson disease: implications for neurological care. Nat. Clin. Pract. Neurol. 2, 136146 (2006).

Article CAS PubMed Google Scholar

Trinh, J. & Farrer, M. Advances in the genetics of Parkinson disease. Nat. Rev. Neurol. 9, 445454 (2013).

Article CAS PubMed Google Scholar

Bandres-Ciga, S., Diez-Fairen, M., Kim, J. J. & Singleton, A. B. Genetics of Parkinsons disease: an introspection of its journey towards precision medicine. Neurobiol. Dis. 137, 104782 (2020).

Article CAS PubMed PubMed Central Google Scholar

Xiao, X. et al. APP, PSEN1, and PSEN2 variants in Alzheimers disease: systematic re-evaluation according to ACMG guidelines. Front. Aging Neurosci. 13, 695808 (2021).

Article CAS PubMed PubMed Central Google Scholar

Pilotto, A., Padovani, A. & Borroni, B. Clinical, biological, and imaging features of monogenic Alzheimers disease. BioMed. Res. Int. 2013, e689591 (2013).

Article Google Scholar

Bertram, L. & Tanzi, R. E. Genomic mechanisms in Alzheimers disease. Brain Pathol. 30, 966977 (2020).

Article PubMed PubMed Central Google Scholar

Moore, B. et al. Developing a gene therapy for the treatment of autosomal dominant Alzheimers disease. Hum. Gene Ther. 34, 10491063 (2023).

Article CAS PubMed Google Scholar

Moore, B. D. & Schaeffer, E. Gene replacement of mutant presenilin1 normalizes -secretase function in models of autosomal dominant Alzheimers disease. Alzheimers Dement. 18, e067938 (2022).

Article Google Scholar

US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT00627588 (2013).

Palfi, S. et al. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinsons disease: a dose escalation, open-label, phase 1/2 trial. Lancet 383, 11381146 (2014).

Article CAS PubMed Google Scholar

Palfi, S. et al. Long-term follow-up of a phase I/II study of prosavin, a lentiviral vector gene therapy for Parkinsons disease. Hum. Gene Ther. Clin. Dev. 29, 148155 (2018).

Article CAS PubMed PubMed Central Google Scholar

Stewart, H. J. et al. Optimizing transgene configuration and protein fusions to maximize dopamine production for the gene therapy of Parkinsons disease. Hum. Gene Ther. Clin. Dev. 27, 100110 (2016).

Article CAS PubMed Google Scholar

Badin, R. A. et al. Gene therapy for Parkinsons disease: preclinical evaluation of optimally configured TH:CH1 fusion for maximal dopamine synthesis. Mol. Ther. Methods Clin. Dev. 14, 206216 (2019).

Article CAS PubMed PubMed Central Google Scholar

US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT03720418 (2022).

Bartus, R. T., Weinberg, M. S. & Samulski, R. J. Parkinsons disease gene therapy: success by design meets failure by efficacy. Mol. Ther. 22, 487497 (2014).

Article CAS PubMed PubMed Central Google Scholar

Khan, S. H. Genome-editing technologies: concept, pros, and cons of various genome-editing techniques and bioethical concerns for clinical application. Mol. Ther. Nucleic Acids 16, 326334 (2019).

Article CAS PubMed PubMed Central Google Scholar

Paschon, D. E. et al. Diversifying the structure of zinc finger nucleases for high-precision genome editing. Nat. Commun. 10, 1133 (2019). This study showcases a novel engineered zinc finger architecture possessing 64-fold greater degrees of configuration, enabling it to target any given base with enhanced precision and specificity.

Article PubMed PubMed Central Google Scholar

Miller, J. C. et al. Enhancing gene editing specificity by attenuating DNA cleavage kinetics. Nat. Biotechnol. 37, 945952 (2019).

Article CAS PubMed Google Scholar

Harmatz, P. et al. First-in-human in vivo genome editing via AAVzinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B. Mol. Ther. 30, 35873600 (2022). This article highlights three in-human clinical studies that successfully and safely employed genome editing for mucopolysaccharidosis I/II and haemophilia B.

Article CAS PubMed PubMed Central Google Scholar

Gillmore, J. D. et al. CRISPRCas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493502 (2021).

Article CAS PubMed Google Scholar

US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04560790 (2022).

US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04122742 (2024).

US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04601051 (2023).

Heidersbach, A. J., Dorighi, K. M., Gomez, J. A., Jacobi, A. M. & Haley, B. A versatile, high-efficiency platform for CRISPR-based gene activation. Nat. Commun. 14, 902 (2023).

Article CAS PubMed PubMed Central Google Scholar

Casas-Mollano, J. A., Zinselmeier, M. H., Erickson, S. E. & Smanski, M. J. CRISPRCas activators for engineering gene expression in higher eukaryotes. CRISPR J. 3, 350364 (2020).

Article CAS PubMed PubMed Central Google Scholar

Colasante, G. et al. In vivo CRISPRa decreases seizures and rescues cognitive deficits in a rodent model of epilepsy. Brain 143, 891905 (2020). This proof-of-principle study highlights the therapeutic potential of CRISPRa in reducing the incidence of spontaneous seizures in vivo.

Article PubMed PubMed Central Google Scholar

Gupta, R. M. & Musunuru, K. Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPRCas9. J. Clin. Invest. 124, 41544161 (2014).

Article PubMed PubMed Central Google Scholar

Chauhan, V. P., Sharp, P. A. & Langer, R. Altered DNA repair pathway engagement by engineered CRISPRCas9 nucleases. Proc. Natl Acad. Sci. USA 120, e2300605120 (2023).

Article CAS PubMed PubMed Central Google Scholar

Xue, C. & Greene, E. C. DNA repair pathway choices in CRISPRCas9-mediated genome editing. Trends Genet. 37, 639656 (2021).

Article CAS PubMed PubMed Central Google Scholar

Yang, H. et al. Methods favoring homology-directed repair choice in response to CRISPR/Cas9 induced-double strand breaks. Int. J. Mol. Sci. 21, 6461 (2020).

Article CAS PubMed PubMed Central Google Scholar

Ceccaldi, R., Rondinelli, B. & DAndrea, A. D. Repair pathway choices and consequences at the double-strand break. Trends Cell Biol. 26, 5264 (2016).

Article CAS PubMed Google Scholar

Lieber, M. R. The mechanism of double-strand DNA break repair by the nonhomologous DNA end joining pathway. Annu. Rev. Biochem. 79, 181211 (2010).

Article CAS PubMed PubMed Central Google Scholar

Stinson, B. M. & Loparo, J. J. Repair of DNA double-strand breaks by the non-homologous end joining pathway. Annu. Rev. Biochem. 90, 137164 (2021).

Article CAS PubMed PubMed Central Google Scholar

Davis, A. J. & Chen, D. J. DNA double strand break repair via non-homologous end-joining. Transl. Cancer Res. 2, 130 (2013).

CAS PubMed Google Scholar

Liang, F., Han, M., Romanienko, P. J. & Jasin, M. Homology-directed repair is a major double-strand break repair pathway in mammalian cells. Proc. Natl Acad. Sci. USA 95, 51725177 (1998).

Article CAS PubMed PubMed Central Google Scholar

Wang, H. & Xu, X. Microhomology-mediated end joining: new players join the team. Cell Biosci. 7, 6 (2017).

Article PubMed PubMed Central Google Scholar

Bhargava, R., Onyango, D. O. & Stark, J. M. Regulation of single strand annealing and its role in genome maintenance. Trends Genet. 32, 566575 (2016).

Read the original:
Gene therapy for CNS disorders: modalities, delivery and translational challenges - Nature.com

Fractyl Healths adeno-associated virus (AAV) GLP-1 pancreatic gene therapy Rejuva/RJVA-001 reduced weight and improved body composition in murine models of obesity alone and after GLP-1 therapy withdrawal.1

These preclinical data were presented at the American Diabetes Association (ADA) 84th Scientific Sessions Meeting, held June 21-24 in Orlando, Florida, and virtually, by Harith Rajagopalan, MD, PhD, cofounder and Chief Executive Officer, Fractyl.1

These data demonstrate that Rejuva can durably improve body composition and fasting glucose, compared to or better than semaglutide, by restoring GLP-1 production in a one-and-done treatment, Rajagopalan said in a statement.2 These data also show Rejuva could help maintain improvements after semaglutide is withdrawn, highlighting our therapys potential to fill an emerging and critical need in the management of obesity and T2D: a reliable, off ramp from chronic GLP-1 drugs that allows people to maintain the weight loss and blood sugar benefits, even as they stop taking these medicines.

Rejuva is designed to enable durable production of GLP-1 in pancreatic islet cells. It is administered via a proprietary, automated, endoscopic delivery device to the pancreas. Fractyl hopes that the gene therapy may address the issue of weight rebound and high rates of discontinuation with GLP-1 drugs such as semaglutide.

READ MORE: Kadimastem and iTolerance Work to Bring Immunosuppression-Free Diabetes Cell Therapy to Trials

The data presented at ADA are from a study that evaluated Rejuva in mice randomized to a single dose of the gene therapy or daily semaglutide injections for 4 weeks, with a crossover at 4 weeks to evaluate Rejuva in mice after semaglutide withdrawal for another 8 weeks compared to placebo.1

The investigators found that in mouse models of diet-induced obesity, Rejuva improved glucose, insulin, and weight more than daily doses of semaglutide. At week 4, Rejuva reduced fat mass by 21% versus 16% of body weight with semaglutide (both P <.0001 versus placebo, P <.05 Rejuva versus semaglutide) while both Rejuva and semaglutide preserved lean mass with a loss of only 5% of body weight (both, P <.0001 versus placebo).1

In mice after semaglutide withdrawal, Rejuva demonstrated a sustained weight loss. At week 8, fat mass rebounded to 1% below baseline (P >.05) in the semaglutide withdrawal group, and semaglutide-withdrawn mice treated with Rejuvamaintained fat reduction of 17% (p<0.01) and weight loss of 22% (P <.0001) at week 8.Looking closer at body composition, treated mice had reduced food intake, primarily fat loss, and improved fasting blood glucose and insulin at 4 and 8 weeks after administration. Rejuva was not associated with any tissue inflammation. The company posits that these data demonstrate feasibility of Rejuva and investigational new drug application (IND)-enabling studies are underway.1

In addition to the compelling durability of weight loss, body composition, and glucose improvements seen in this model, we are pleased that isolated, genetically modified islets from Rejuva-treated mice show this release of GLP-1 in response to nutrients, Timothy Kieffer, Chief Scientific Officer, Fractyl Health, added.2 We believe this clearly demonstrates that Rejuva can mimic the physiologic release of GLP-1 that occurs naturally in the human body.

Go here to see the original:
Gene Therapy Improves Body Composition in Mice Models of Obesity Alone and After Semaglutide Withdrawal - CGTLive

The Food and Drug Administration on Thursday approved Elevidys, Sarepta Therapeutics gene therapy for Duchenne muscular dystrophy, for nearly all patients with the fatal muscle-wasting disease, dramatically expanding the initial, narrow authorization handed down last year.

The decision will likely be greeted by many families and doctors as a turning point in the fight against the muscle-wasting disease, even if its not nearly the seismic shift some had hoped for just a couple of years ago.

Gene therapy had long been seen as one of the approaches that might cure or at least halt the fatal condition. But clinical trials have presented a far murkier reality. Three different randomized studies of Duchenne gene therapies, including the only two conducted with Elevidys, have failed to reach their primary endpoints. And reports have circulated of boys Duchenne mostly affects boys whose conditions begin to decline just a couple years after treatment.

STAT+ Exclusive Story

Already have an account? Log in

Already have an account? Log in

Already have an account? Log in

Get unlimited access to award-winning journalism and exclusive events.

Read more from the original source:
FDA approves Sarepta's Duchenne gene therapy for nearly all patients - STAT

Genethons GNT0004, an investigational recombinant adeno-associated virus (AAV) vector-based gene therapy intended to treated Duchenne muscular dystrophy (DMD), has demonstrated the ability to produce expression of microdystrophin, among other signs of efficacy, in a phase 1/2/3 clinical trial.1,2 The data were presented by Francesco Muntoni, MD, the principal investigator of the trial and the chair of paediatric neurology at University College London Great Ormond Street Institute of Child Health, at the Myology 2024 International Scientific Congress, held April 22 to 25, in Paris, France.

Among 5 patients treated in the multicenter clinical trial, 2 patients received the studys lower dose (1x1013 vg/kg) and 3 patients received the studys higher dose (3x1013 vg/kg). For the 3 patients who were treated at the higher dose, immunohistochemistry showed that a mean of 54% of muscle fibers (range, 15% to 85%) were expressing microdystrophin, the therapeutic transgene delivered by GNT0004, at 8 weeks posttreatment. Genethon noted that alongside these expression levels, a mean of 1.2 vector genome copies per muscle fiber nuclei (range, 0.4 to 2.5) were observed. Furthermore, at 12 weeks posttreatment for these patients, levels of CPK, a biomarker for muscular destress, had been reduced by a mean of 74% (range, 50% to 87%). In the first patient who received the higher dose, the decrease was noted to be persistent at up to 18 months of follow-up. Genethon stated that this patient also showed positive trends on functional assessments at 1 year posttreatment including the North Star Ambulatory Assessment, the 10 Meter Walk Test, and ability to stand up.

DMD is a rare, X-linked progressive disease caused by mutations in the dystrophin gene, leading to dystrophin deficiency in muscles, Muntoni and colleagues wrote in their abstract.2The lack of dystrophin in myocytes results in progressive muscle degeneration that manifests primarily as muscle weakness and early death during the second or third decade of life, with the most common cause of death being cardiorespiratory failure. GNT0004 is a recombinant serotype 8 AAV vector-based gene therapy containing a shortened, but functional version of DMD gene (hMD1) optimized with key functional domains of full-length dystrophin. The hMD1 transgene is driven by aSpc5.11 promotor, which leads to expression in skeletal and cardiac muscle target tissues.

In terms of safety, Geneton reported good tolerability of GNT0004 in combination with transient immunological prophylactic treatment.1 The organization noted that the trial, which began in 2021, had previously been paused after a serious adverse event (SAE) occurred in the first patient treated, but that the trial resumed in late 2022 after the SAE resolved.

The trial recruited patients aged 6 to 10 years old who are ambulant. The group of 5 who were treated includes 1 patient that was treated in the United Kingdom, with the other 4 having been treated in France. Genethon stated that it is currently making preparations for the pivotal European phase of the study in concert with the European Medicines Agency after having received a positive opinion from the Data Monitoring Committee.

In addition to DMD, Genethon is developing gene therapy products of a range of other diseases.3 Notably, clinical results for GNT-003 (GNT0003), an investigational AAV vector-based gene therapy being evaluated for the treatment of Crigler-Najjar syndrome in a phase 1/2 clinical trial (NCT03466463), were reported inThe New England Journal of Medicine in August 2023.4 The patients with the rare liver disease who received the trials higher dose (n = 3; 51012vg/kg) had a decrease in bilirubin levels and were not receiving phototherapy at least 78 weeks after vector administration.

Although our study is small, among the patients who received the dose of 51012vg/kg, GNT0003 restored UGT1A1 activity to levels that permitted suspension of phototherapy, and the efficacy persisted at 18 months after the treatment, study author Lorenzo DAntiga, MD, of the Department of Pediatric Hepatology, Gastroenterology, and Transplantation at Hospital Papa Giovanni XXIII, in Bergamo, Italy, and colleagues wrote.5A test of replication in a larger, well-characterized cohort of patients will be important.

View original post here:
Genethon's Duchenne Muscular Dystrophy Gene Therapy GNT0004 Produces Expression of Microdystrophin in Phase ... - CGTLive

Enlarge / Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research within the Food and Drug Administration on March 18, 2021 in Washington, DC.

The Food and Drug Administration (FDA) on Thursday announced expanded approval for a gene therapy to treat Duchenne muscular dystrophy (DMD)despite the fact that it failed a Phase III clinical trial last year and that the approval came over the objections of three of FDA's own expert review teams and two of its directors.

In fact, the decision to expand the approval of the therapycalled Elevidys (delandistrogene moxeparvovec-rokl)appears to have been decided almost entirely by Peter Marks, Director of the FDA's Center for Biologics Evaluation and Research.

Elevidys initially gained an FDA approval last year, also over objections from staff. The therapy intravenously delivers a transgene that codes for select portions of a protein called dystrophin in healthy muscle cells; the protein ismutated in patients with DMD. Last year's initial approval occurred under an accelerated approval process and was only for use in DMD patients ages 4 and 5 who are able to walk. In the actions Thursday, the FDA granted a traditional approval for the therapy and opened access to DMD patients of all ages, regardless of ambulatory status.

"Todays approval broadens the spectrum of patients with Duchenne muscular dystrophy eligible for this therapy, helping to address the ongoing, urgent treatment need for patients with this devastating and life-threatening disease," Marks said in the announcement Thursday. "We remain steadfast in our commitment to help advance safe and effective treatments for patients who desperately need them."

The move, which follows a string of controversies in recent years of the FDA issuing questionable approvals over the assessments of advisors and its own staff, has quickly drawn criticism from agency watchers.

In a blog post Friday, a notable pharmaceutical industry expert and commentator, Derek Lowe, admonished the approval. Lowe expressed concern that the agency seems to be tilting toward emotional rhetoric and the will of patient advocates over scientific and medical evidence.

"It appears that all you need is a friend high up in the agency and your clinical failures just aren't an issue any more," he wrote. "Review committees aren't convinced? Statisticians don't buy your arguments? Who cares! Peter Marks is here to deliver hot, steaming takeout containers full of Hope. ... And while I realize that this may make me sound like a heartless SOB, I think this is a huge mistake that we will be paying for for a long time."

In a comment to Stat News, former FDA chief scientist Luciana Borio echoed concerns about how decisions like this will affect the agency in the longer term.

"I dont know what to say. Peter Marks makes a mockery of scientific reasoning and approval standards that have served patients well over decades," said Borio, who has also opposed earlier controversial approvals. "This type of action also promotes the growing mistrust in scientific institutions like the FDA."

In a series of review documents and memos released by the FDA, the divide between Marks and agency staff is abundantly clear. A review by FDA statisticians concluded that the collective clinical trial results "do not suggest there is substantial evidence to support the effectiveness of [Elevidys] for the expanded indication to all DMD patients and do not support the conversion of accelerated to traditional approval."

A joint review from the agency's Clinical and Clinical Pharmacology teams likewise concluded that the "totality of the data does not provide substantial evidence of effectiveness of Elevidys for treatment of ambulatory DMD patients of any age" and that the results "argue against" expanding access.

In a memo, Lola Fashoyin-Aje, Director of the Office of Clinical Evaluation in the Office of Therapeutic Products (OTP), and Dr. Nicole Verdun, Super Office Director of the OTP, concluded that the clinical results "cast significant uncertainty regarding the benefits of treatment of DMD with Elevidys." The two directors found the primary clinical trial endpoint results were "not statistically significant" and smaller analyses looking at secondary endpoints of specific patient measuressuch as the time it takes patients to rise from the floor or walk 10 meterswere "inconclusive," in some cases "conflicting," and overall illustrated the "unreliability of exploratory analyses to support regulatory decision-making."

In a memo of his own, Marks agreed that primary endpoint result of the trialbased on scores on a standardized assessment of motor function in patientsdid not show a statistically significant benefit. But he argued that the secondary endpoints were convincing enough for him. Marks wrote:

Specifically, although acknowledging that the Applicants randomized study of Elevidys failed to meet its statistical primary endpoint ... I find that the observations regarding the secondary endpoints and exploratory endpoints are compelling and, combined with other data provided in the efficacy supplement and the original [Biologics License Application], meet the substantial evidence of effectiveness standard ...

If Marks had not overruled the agency's reviewers and directors, Fashoyin-Aje wrote that she would have recommended the therapy's maker, Sarepta, conduct "an additional adequate and well-controlled study of Elevidys in the subgroup(s) of patients for which [Sarepta] believes the effects of Elevidys to be most promising." However, Marks' decision to approve renders the possibility of such a trial "highly infeasible to explore in a post-approval setting," she wrote.

See the article here:
Top FDA official overrules staff to approve gene therapy that failed trial - Ars Technica

Berlin, Germany, June 21, 2024 Today Bayer AG, together with Charit Universittsmedizin Berlin, presented plans for the construction of the Berlin Center for Gene and Cell Therapies. The project is being substantially financed and supported by Germanys Federal Government as well as the State of Berlin. The aim of the joint project is to bring these groundbreaking technologies to patients more quickly while creating a leading biotech ecosystem for innovative therapies in Berlin.

The potential for cell and gene therapies (CGTs) is considered to be enormous. By targeting diseases at the genetic and cellular level, CGTs could offer options to people for whom conventional therapies have failed or where no effective treatment is currently available.

In order to translate basic research into benefits for patients faster, Charit and Bayer will establish the Berlin Center for Gene and Cell Therapies on the Bayer campus at Berlin Nordhafen. The center will support start-ups bringing their innovative approaches in the area of cell therapies and gene therapies into clinical development. To achieve this, the center will include a so-called incubator with fully equipped laboratory space and a production area certified according to the standards of good manufacturing practice (GMP). Incubators are facilities that accompany start-ups developing their innovative ideas and helping them build viable business models. These early-stage companies will receive advice on regulatory requirements, clinical trials, patent rights and business development. To operate the incubator, Bayer and Charit will establish a joint public-private, non-profit company with limited liability. Charit will own 67 percent of this company, with Bayer owning the remaining 33 percent.

The Berlin Center for Gene and Cell Therapies will bring together research, development and the manufacturing of cell therapies and gene therapies in the heart of Berlin. Purposely embedding it within the Berlin ecosystem, a European capital with a large number of biomedical and healthcare facilities, it is intended to become a creative and interactive hub for biotech innovations in the area of CGT. The project is funded by both the Federal Ministry of Education and Research and the State of Berlin. Construction is planned to begin in 2025.

Olaf Scholz, Federal Chancellor of Germany: "With the kick-off of the new translation center, we are also celebrating a unique form of collaboration between science, industry and politics. This institution will become the core of an entire organism of gene and cell-based therapies. To achieve this, we need scientists and entrepreneurs who see both the smallest details in the cell nucleus as well as the big picture: the medicine of the future that provides answers to the big questions that Rudolf Virchow already posed. Here in Germany we have both: bold research and innovative companies. I wish you every success with this visionary project!"

Bettina Stark-Watzinger, Federal Minister of Education and Research: Gene and cell therapies offer a tremendous opportunity for more targeted and therefore better treatment of patients. Currently, however, the path from the research laboratory to the patient's bedside often still takes too long. With the translation center for gene and cell therapies, we are now taking a big step forward in Germany. Science and industry are coming together in one location to turn ideas into reality and to help translate scientific findings into medical practice more quickly through spin-offs and start-ups. As an essential component of the National Strategy for Gene and Cell Therapies, the Federal Ministry of Education and Research is supporting the establishment of the Center with around

80 million euro. In doing so, we are once again strengthening Germany's position as a leading location for biomedical innovations.

Prof. Dr. Karl Lauterbach, Federal Minister of Health: Targeted gene therapies, personalized cancer vaccines and novel antibody-drug conjugates, together with artificial intelligence, will open a new era in medicine and entirely new prospects for patients. These revolutionary treatment approaches place high demands on laboratories, hospitals and doctors. This joint project of Bayer and Charit is an ideal partnership to learn together and make rapid progress.

Bill Anderson, Chairman of the Board of Management (CEO) of Bayer AG: Despite great advances in research and technology, there are still many diseases that are without cure and which affect the lives of millions. To these people, cell and gene therapies offer great hope. Only through close partnerships across borders, new approaches and quick action can we make real progress towards our objective of curing diseases that were long considered incurable.

Stefan Oelrich, Member of the Board of Management, Bayer AG and President of Bayers Pharmaceuticals Division: The close proximity between research and production within the Berlin Center for Gene and Cell Therapies will be unique in Germany. Together with the Charit we want to help translate scientific knowledge in the area of cell therapies and gene therapies into innovative treatment approaches for patients as quickly as possible. With the Berlin Center for Gene and Cell Therapies, it is our vision to establish a biotech ecosystem, which unites different players, providing international appeal way beyond the city of Berlin.

Prof. Dr. Heyo K. Kroemer, Chief Executive Officer of Charit: Cell therapies and gene therapies represent a major medical advance; they can help where conventional methods reach their limits. As these are highly innovative drugs, their development, however, is much more complex than that of other medicines. If we want to bring these therapies to patients as quickly as possible, we need to take new routes. With the intensified partnership between Charit and Bayer, we want to initiate structural development to bring Berlin to the forefront of this pioneering technology both nationally and internationally. In doing so, we also create and maintain value and thus jobs in the country. This is a big step in Berlin, for Berlin and for Germany.

Astrid Lurati, Chief Financial and Infrastructure Officer of Charit: "As part of this project, the two partners Charit and Bayer are combining their respective expertise to further advance the developments in the field of gene and cell therapy both nationally and internationally. This approach is unique in Germany and demonstrates the innovation power of Berlin and its major healthcare players in their efforts to reimagine the medical care of tomorrow already today. The extensive support, which we are receiving both from the State of Berlin as well as the Federal Government underlines the importance of this project. With the Berlin Center for Gene and Cell Therapies we are breaking new ground together and I would like to thank everyone involved for the excellent cooperation."

Kai Wegner, Governing Mayor of Berlin: Berlin is a strong and leading location for science, research and medicine and therefore for the healthcare industry as a whole. The newly emerging translation center for gene and cell therapies is an excellent example of this. The State of Berlin has supported this lighthouse project from the beginning as we are convinced of the potential that gene and cell therapies provide. The collaboration between Charit and Bayer in one of the most innovative areas of medicine is a clear signal that together we can make Berlin and Germany a pioneer in this field. It is our common goal to help more patients with the most modern therapies, where todays medicine still reaches its limits. In addition, the location provides an excellent environment, which we will continue to strengthen by further developing the Bayer site into a life science campus.

Franziska Giffey, Mayor and Berlin State Senator for Economic Affairs, Energy and Public Enterprises: The close collaboration between companies and the excellent research in the city is a recipe for success to achieve our goal of making Berlin the number one innovation hotspot in Europe. With the Bayer and Charit translation center for gene and cell therapies we are moving a big step closer to reaching this goal. It brings together two internationally renowned medical pioneers and will benefit from its location in Berlin, one of the most successful start-up ecosystems in the world. The new center has enormous economic potential and will attract talent and investment. This is very good news for the growing business location of Berlin.

The Berlin Center for Gene and Cell Therapies is being developed by iQ spaces, a project developer specialized in laboratory real estate, on the Bayer campus at Berlin Nordhafen. Across 18,000 sqm, the ten-story building is divided into an incubator with fully equipped laboratory and office space to accommodate 15 to 20 start-ups in various stages of development, as well as a GMP-certified manufacturing facility for the development of cell and gene therapies up to clinical phase II. The building was designed by the architectural firm HENN.

About cell therapies and gene therapies Cell therapies and gene therapies (Advanced Therapy Medicinal Products, ATMPs) are among the most important innovations in the healthcare sector. They have the potential to fundamentally change the treatment of cancer, autoimmune diseases, neurodegenerative diseases and many rare genetic diseases. The novel therapies are based on genes, tissues or cells and therefore often contain living components. These products, which are therefore also referred to as living drugs, can be better tailored to individual patients than traditional medicines and are particularly suitable for the treatment of diseases that were previously untreatable or difficult to treat. Although several hundred clinical studies for the development of cell therapies and gene therapies are currently ongoing, only a small number of such products is currently approved in Europe. The goal of Bayer and Charit is for the Berlin Center for Gene and Cell Therapies to bridge this translation gap.

About Charit Universittsmedizin Berlin With more than 100 departments and institutes across four campuses and 3,293 beds, Charit Universittsmedizin Berlin is one of Europes largest university medical centers. At Charit, the areas of research, teaching, and medical and patient care are closely interconnected. Averaging about 20,000 employees Charit-wide and some 23,500 across the entire group of companies, Berlins university medicine organization remained one of the capital citys largest employers in 2023. Charit is a leader in diagnosis and treatment of particularly severe, complex, and rare diseases and health conditions. A medical school and university medical center in one, Charit enjoys an outstanding reputation worldwide, combining first-class patient care with excellence in research and innovation, state-of-the-art teaching, and high-quality training and education. Everything Charit does revolves around people and their health. Charit pursues translational research in which scientific findings are applied to prevention, diagnostics, and treatment and clinical observations inform new approaches in research in turn. At Charit, the goal is to actively help shape the medicine of the future to benefit patients. https://www.charite.de/en/

About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, Health for all, Hunger for none, the companys products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to http://www.bayer.com.

Find more information at https://pharma.bayer.com/ Follow us on Facebook: http://www.facebook.com/bayer

Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayers public reports which are available on the Bayer website at http://www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

More here:
Berlin Center for Gene and Cell Therapies kicked off in Berlin - The Palm Bayer

The U.S. Food and Drug Administration (FDA) has expanded its approval of Elevidys (delandistrogene moxeparvovec-rokl), authorizing the one-time gene therapy for individuals with Duchenne muscular dystrophy (DMD) ages 4 and older regardless of their ability to walk. Previously, the treatment had been approved for DMD children ages 4 to 5 who could walk.

Doug Ingram, president and CEO of Elevidys developer Sarepta Therapeutics, said the expanded approval is a defining moment for the Duchenne community as well as a watershed occasion for the promise of gene therapy and a win for science, in a company press release.

The move was welcomed with excitement by the muscular dystrophy community.

We are delighted that the FDA has expanded the label for Elevidys, Sareptas gene therapy for Duchenne muscular dystrophy to include ambulatory and non-ambulatory Duchenne patients who are older than 4 years of age, Debra Miller, founder and CEO of CureDuchenne, said in a statement to Muscular Dystrophy News.

Pat Furlong, founding president and CEO of Parent Project Muscular Dystrophy (PPMD), said the FDAs decision represents a monumental leap forward in our collective efforts to end Duchenne muscular dystrophy.

By expanding the labels age inclusion and removing ambulation restrictions, Elevidys can now reach and benefit a more diverse population of Duchenne patients, Furlong said in a PPMD press release, adding patients and families need treatment options, and we applaud the expansion of these options.

Duchenne is caused by mutations in the gene DMD, which result in virtually no production of dystrophin, a protein that normally helps to prevent damage in muscle cells. Lacking functional dystrophin, muscle cells of people with Duchenne accumulate atypical damage over time, which ultimately drives symptoms like muscle weakness and wasting.

Elevidys is designed to deliver a gene encoding micro-dystrophin, a shortened but functional version of the dystrophin protein, to muscle cells.

While more patients now are eligible for the therapy, it remains contraindicated, or not recommended for use, among individuals who have any deletion in exon 8 and/or exon 9 in the DMD gene. It also is not recommended for patients with high levels against AAVrh74, the viral vector that the therapy uses to deliver its genetic cargo to cells. Exons are the coding sections that have the information to produce proteins.

Almost exactly one year ago, the FDA granted Elevidys accelerated approval to treat children with DMD ages 4 to 5 who are able to walk. Accelerated approval is a mechanism that allows the FDA to authorize a therapy based on early clinical data suggesting that the treatment will likely benefit patients. As a condition of accelerated approval, drug developers need to conduct additional clinical testing to prove the treatments benefit.

With the new expansion, Elevidys now is indicated to treat patients ages 4 and older, irrespective of whether or not they are able to walk.

The initial approval of Elevidys was a significant milestone, and the expanded indication means clinicians now have a treatment option for the great majority of boys and young men living with Duchenne, said Jerry Mendell, MD, senior advisor of medical affairs at Sarepta and co-inventor of Elevidys. (DMD primarily affects boys and men, though Elevidys is approved to treat the condition irrespective of gender or biological sex.)

Sarepta offers a program called SareptAssist, which includes resources for financial assistance and preparing for treatments. The program can be contacted by phone at 1-888-727-3782.

The FDAs expansion was supported largely by data from the Phase 3 EMBARK trial (NCT05096221), which tested the therapy against a placebo in more than 120 boys with DMD ages 4 to 7. Although the study missed its main goal, the results showed that Elevidys significantly outperformed the placebo in several key secondary measures of motor function one being the time it took patients to walk 10 meters (about 33 feet) or rise from a lying position.

According to the FDA, these findings were compelling and indicate clinical benefit compared to [a] placebo, leading the agency to grant full approval for Elevidys in DMD patients who can walk. The agency noted that common side effects of Elevidys include vomiting, nausea, acute liver injury, fever, and low platelet counts, called thrombocytopenia.

[This decision] marks a pivotal moment for the community, offering renewed hope and tangible progress in our fight against DMD.

Although Elevidys use in ambulatory (able-to-walk) patients is now traditionally approved, its use in nonambulatory patients is under accelerated approval pending additional data to confirm its benefit in this population. Sarepta is running a separate Phase 3 trial, dubbed ENVISION (NCT05881408), to test Elevidys in DMD patients who are older and/or nonambulatory.

Assuming that the results are positive, ENVISION is expected to serve as a confirmatory study to support full traditional FDA approval of Elevidys in DMD patients who cannot walk. ENVISION is still recruiting patients at sites in Belgium, Italy, Japan, Spain, and the U.K.

The full approval for all ambulant patients and accelerated approval for all non-ambulant patients is not only a scientific accomplishment but a major source of hope for countless families affected by this relentless disease, Barry Byrne, MD, PhD, chief medical advisor at the Muscular Dystrophy Association, said in a press release from the advocacy group.

Sharon Hesterlee, PhD, the associations chief research officer, added that the approval marks a pivotal moment for the community, offering renewed hope and tangible progress in our fight against DMD.

Read more here:
Elevidys DMD gene therapy now FDA-approved for age 4 and older - Muscular Dystrophy News

Whats going on here?

Sarepta Therapeutics' shares surged around 36% in premarket trading after the FDA expanded its approval of the gene therapy Elevidys.

What does this mean?

Sarepta received full FDA approval for Elevidys for ambulatory patients aged four and above and accelerated approval for those who cannot walk. This move significantly boosts the therapys market reach, with projections anticipating sales to hit $3 billion by 2025 and peak at $5 billion by 2027. In 2023, Elevidys generated $200.4 million in revenue, with expectations set to soar to $991.91 million this year. Given that Duchenne Muscular Dystrophy (DMD) affects roughly one in 3,500 male births worldwide, Elevidys' expanded approval now targets about 13,000 US patients covering nearly 90% of the US DMD market.

Why should I care?

For markets: The gene therapy gold rush.

In the evolving landscape of gene therapies for DMD, Sarepta's Elevidys is positioned to be the dominant player with no substantial competition until post-2027. RegenxBio is exploring early to mid-stage trials for a competing therapy, while Pfizer faced a setback with a recent late-stage trial failure. This dominance translates into significant market stability for Sarepta, backed by robust financial forecasts.

The bigger picture: The horizon looks bright.

With the global DMD treatment market projected to grow to $11.47 billion by 2034, the expanded use of Elevidys places Sarepta in a commanding position. The company's investor call scheduled for 08:30 am ET is expected to shed light on strategic plans moving forward. At $3.2 million per treatment, Elevidys might be one of the priciest therapies globally, but its value proposition and market penetration could redefine the treatment landscape for DMD.

Originally posted here:
Sarepta Therapeutics' Gene Therapy Gets Major FDA Approval - Finimize

By Mariam Sunny and Bhanvi Satija

June 21 - Sarepta Therapeutics shares surged as much as 40% to a more than three-year high on Friday as an expanded use approval cemented its dominant position in the gene therapy market for Duchenne muscular dystrophy .

At current levels of $163.88, stock was set to add nearly $4 billion to the company's market value if gains hold.

On Thursday, the U.S. FDA granted traditional approval for the therapy, Elevidys, in patients four years and above who can walk, as well as an accelerated approval for those who cannot.

The health regulator's expanded approval was based on the therapy meeting its secondary goals of improvement in factors like time taken by patients to rise from the floor and a 10-meter walk or run, even though it had failed to meet its primary goal of improving motor functions as assessed by a scoring system.

The FDA decision was the best case scenario predicted by analysts, with BMO Capital Market's Kostas Biliouris estimating that Elevidys could be given to about 13,000 patients, or nearly 90% of U.S. patients.

Given the high demand and acceptable safety, analysts flagged manufacturing concerns and insurance coverage for newly added patients as limiting factors.

The company is working on a new so-called suspension process for commercial production of Elevidys, which could be more beneficial as the therapy moves to a broader outside U.S. population, CEO Doug Ingram said in a conference call with analysts and investors.

"We've already done engineering runs up to 2,000 liters... and it will give us not only more materials down the road years from now, but also significantly reduce the cost of goods," Ingram added.

The company uses Catalent and Thermo Fisher Scientific as contract manufacturers for its gene therapy.

Elevidys is among the most expensive treatments in the world with a list price of $3.2 million, and Ingram said on Friday the company does not intend to modify the price.

Sales of the therapy came in at $200.4 million in 2023. BMO's Biliouris said those sales showed that Sarepta had "done an amazing job".

"Commercially, they have been perhaps more successful than any other gene therapy, with the only exception being Zolgensma from Novartis," Biliouris said in an interview ahead of the approval.

Biliouris now expects Elevidys to be the "dominant" DMD gene therapy with no near-term competition until later than 2027.

DMD is an inherited progressive muscle-wasting disorder that affects an estimated one-in-3,500 male births worldwide, according to the U.S.-based National Organization for Rare Disorders.

The decision also follows concerns around an "uphill battle" to secure traditional approval after the therapy failed to meet the main goal in a key confirmatory late-stage trial.

The global treatment market for DMD - including gene therapies and other drugs - is expected to grow to $11.47 billion by 2034, according to ResearchandMarkets.com.

RegenxBio is testing a rival gene therapy in early- to mid-stage, while Pfizer's treatment recently failed in a late-stage study.

This article was generated from an automated news agency feed without modifications to text.

Milestone Alert! Livemint tops charts as the fastest growing news website in the world Click here to know more.

3.6 Crore Indians visited in a single day choosing us as India's undisputed platform for General Election Results. Explore the latest updates here!

Published: 21 Jun 2024, 11:01 PM IST

See the original post:
Sarepta surges as investors cheer expanded use of gene therapy - Mint