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Translarna: Update for Non-Ambulatory Patients with DMD

PTC Therapeutics Announces that The Committee for Medicinal Products for Human Use (CHMP) Recommendation of Translarna ™ (ataluren) Label Update for Non-Ambulatory Patients with Duchenne Muscular Dystrophy

Original press release > SOUTH PLAINFIELD, N.J., June 29, 2020,/PRNewswire/ — PTC Therapeutics, Inc.

 

PTC Therapeutics, Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended by a majority of votes to remove the statement “efficacy has not been demonstrated in non-ambulatory patients” from the Summary of product characteristics (SmPC) for Translarna™ (ataluren). This label change enables healthcare professionals to use their clinical judgement to make treatment decisions for their patients on Translarna who have lost ambulation. The change also should support reimbursement agencies granting continued access to Translarna for patients who become non-ambulatory during their treatment. The CHMP’s positive opinion is subject to final approval by the European Commission, which is typically granted in a two-month time frame.

 

Stuart W. Peltz, Ph.D., Chief Executive Officer of PTC Therapeutics – “We are excited to see that the CHMP adopted the positive opinion for this label modification allowing patients who become non-ambulatory to continue to use Translarna. All nonsense mutation Duchenne patients should be able to benefit from continued Translarna use, ensuring they have the best chance of preserving muscle function for as long as possible.”

 

Translarna is the only treatment for the underlying cause of Duchenne caused by a nonsense mutation and works by restoring dystrophin production. The EMA approves it for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD) in ambulatory patients aged two years and older. Real-world evidence and clinical trials have demonstrated the potential of Translarna to slow disease progression and improve outcomes before and beyond the loss of ambulation:

  • In a long-term, open-label extension study (Study 019), Translarna preserved lung function in non-ambulatory patients for an additional four years compared with patients treated with standard of care from a long-term natural history study (the Cooperative International Neuromuscular Research Group (CINRG) natural history database of Duchenne patients).
  • Data from the STRIDE Registry, the first international drug registry for Duchenne patients receiving Translarna, demonstrated that boys treated with Translarna and standard of care (SoC) preserved the ability to walk for years longer than those on SoC alone, as well as experienced a slower decline in lung function.
  • Children treated with Translarna in a real-world setting as part of the STRIDE registry were able to walk independently for an additional 3.5 years compared with a propensity-score matched cohort in the CINRG natural history study, with a median age at loss of ambulation of 14.5 years and 11 years, respectively (72% relative risk reduction).
  • There was a trend toward a delay in the age at the decline in pulmonary function in STRIDE patients compared with CINRG patients, as measured by predicted FVC < 50% and FVC < 1 L.4
  • These data suggest that treatment with ataluren, in addition to SoC, may delay loss of ambulation, as well as pulmonary functional decline, in patients with nmDMD.
  •  View the original content here.

About Translarna (ataluren)

Translarna (ataluren), discovered and developed by PTC Therapeutics, Inc., is a protein restoration therapy designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation. A nonsense mutation is an alteration in the genetic code that prematurely halts the synthesis of an essential protein. The resulting disorder is determined by which protein cannot be expressed in its entirety and is no longer functional, such as dystrophin in Duchenne muscular dystrophy. Translarna, the tradename of ataluren, is licensed in the European Economic Area for the treatment of nonsense mutation Duchenne muscular dystrophy in ambulatory patients aged two years and older. Ataluren is an investigational new drug in the United States.

 

Ataluren in Canada

At this moment, PTC Therapeutics has not applied for marketing approval with Health Canada.

 

About PTC Therapeutics

PTC is a science-driven, global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders. PTC’s ability to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines and their mission to provide access to best-in-class treatments for patients who have an unmet medical need. To learn more about PTC, please visit them at www.ptcbio.com. Read more here > La Force DMD Blog / PTC Therapeutics.

 

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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.

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Positive Safety and Efficacy Data from Micro-Dystrophin Gene Therapy

Sarepta Therapeutics Announces Positive Safety and Efficacy Data from the SRP-9001 Micro-Dystrophin Gene Therapy Trial Published in JAMA Neurology

 

Press release here > CAMBRIDGE, Mass., June 15, 2020 (GLOBE NEWSWIRE)

Sarepta Therapeutics, Inc. announced safety and tolerability data at one year from four Duchenne muscular dystrophy (DMD) clinical trial participants who received SRP-9001 micro-dystrophin (AAVrh74.MHCK7.micro-dystrophin) have been published in JAMA Neurology. 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.

 

Louise Rodino-Klapac, Ph.D., senior vice president of gene therapy, Sarepta Therapeutics –  “We are encouraged by the successful and safe systemic delivery of our micro-dystrophin transgene from our AAVrh74 viral capsid and targeted muscle expression results, demonstrating the safety and efficacy of SRP-9001 gene transfer maintained over one year in this cohort of participants living with Duchenne muscular dystrophy. Following the 9-month update we shared last year, the peer-reviewed publication of these results in JAMA Neurology further supports the potential for SRP-9001 to provide clinically meaningful functional improvements in terms of speed and magnitude of improvement for patients with DMD.  Study 102, our randomized, double-blind, placebo-controlled study of SRP-9001, is ongoing and we look forward to sharing the results in early 2021 as we work toward our ultimate goal of profoundly improving the lives of as many patients living with DMD 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 at a dose of 2×1014 VG/kg. The therapy was safe and tolerable in all participants over the one-year time period. All adverse events were considered mild or moderate, and there were no serious adverse events or evidence of complement activation.  At 12 weeks, muscle dystrophin levels demonstrated a mean of 81.2% muscle fibers 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%. All participants had confirmed vector transduction and showed functional improvement on the North Star Ambulatory Assessment scale (NSAA) and reduced creatine kinase (CK) levels that were maintained through one year.

 

Jerry Mendell, M.D., the study’s co-author and principal investigator with the Center for Gene Therapy in the Abigail Wexner Research Institute at Nationwide Children’s Hospital –  “Duchenne muscular dystrophy is difficult to treat, and more options are needed to have the potential to alter the course of the disease. We are very pleased to report the successful delivery of the transgene to the nuclei corresponding to robust expression and proper localization of micro-dystrophin. This coincides with improvements in functional measurements in study participants who received SRP-9001. These results, together with biological and clinical markers of efficacy, provide proof-of-concept support for the continuation of clinical trials for assessment of SRP-9001 using single-dose gene therapy in participants with Duchenne.”

 

 

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 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.

 

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.

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