Positive clinical results from MOMENTUM

Sarepta Therapeutics announces positive clinical results from MOMENTUM, a phase 2 clinical trial of SRP-5051 in patients with Duchenne muscular dystrophy amenable to skipping exon 51.

Original press release > CAMBRIDGE, Mass., Dec. 07, 2020 (GLOBE NEWSWIRE)

Overview

  • Results from the multiple-ascending dose trial demonstrate proof-of-concept for SRP-5051 and support continued dose escalation.
  • At a total dose exposure approximately 10x lower than eteplirsen, SRP-5051 at 20 mg/kg showed enhanced tissue exposure, greater exon skipping, and greater dystrophin production with no negative renal or other laboratory findings.
  • These are the first clinical results from the Company’s peptide phosphorodiamidate morpholino oligomer (PPMO) technology, its next-generation chemistry platform.

Sarepta Therapeutics, Inc. announced results from the ongoing MOMENTUM study (Study 5051-201), a global Phase 2 clinical trial of SRP-5051, its next-generation treatment patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping. This is the first clinical data from SRP-5051, an investigational treatment that uses Sarepta’s peptide phosphorodiamidate morpholino oligomer (PPMO) technology. PPMO technology includes a proprietary cell-penetrating peptide conjugated to Sarepta’s PMO backbone to increase cellular uptake of drug in the muscle tissue.

Results from Part A of the multi-ascending dose MOMENTUM study found consistently higher tissue exposure, exon-skipping and dystrophin production in patients taking a monthly dose of SRP-5051 compared to baseline. SRP-5051 was generally well-tolerated across all doses studied, with no clinical or laboratory findings reported. The results support continued dose escalation of SRP-5051 and further clinical development.

 

Doug Ingram, president and chief executive officer, Sarepta – “Sarepta’s PMO RNA technology is a vital platform on which we design therapies to treat those with Duchenne muscular dystrophy. Our next-generation PPMO technology is designed to increase cell penetration with the goal of offering significantly improved efficacy with more convenient dosing in Duchenne patients amenable to exon skipping. While patient numbers in each dose arm are small, the higher tissue concentration, exon skipping and dystrophin production in the 20 mg/kg dosing group were observed at an early 12-week time point and with far less cumulative drug exposure when compared to our current PMO technology. We know from our experience with PMOs that exon-skipping and dystrophin increase over time, and these results along with our preclinical experience, give us confidence as we dose escalate and continue to advance our PPMO exon-skipping therapies for Duchenne, including another five potential therapies that have already been designed, and explore the utility of the PPMO RNA platform for new disease indications.”

 

Compared to a control group of Duchenne patients from the PROMOVI study who received biopsies at 24 weeks after taking a weekly 30 mg/kg dose of eteplirsen, once-monthly dosing of SRP-5051 resulted in higher muscle concentration, increased exon-skipping and dystrophin at 12 weeks. A dose-dependent increase in exon-skipping and dystrophin was observed, with patients in the 20 mg/kg dose group of SRP-5051 seeing a 1.6-fold increase in exon skipping (n=4) and a 5-fold increase in the % of normal dystrophin (n=2) when compared to the group taking eteplirsen at 24 weeks.

The incidence of adverse events in the MOMENTUM study was similar across all dosed cohorts and does not suggest dose dependency. One treatment-emergent event, unrelated to the study drug, occurred in the 4 mg/kg dose group. No clinical or laboratory findings were observed. Full results will be presented at a future medical meeting.

About MOMENTUM (SRP-5051-201)

MOMENTUM is a multi-arm, ascending dose study designed to identify the maximum tolerated dose of SRP-5051. Informed by Study 5051-101, a single ascending dose study of SRP-5051, patients in the MOMENTUM study will receive monthly intravenous (IV) infusions of SRP-5051, starting at 4 mg/kg and ascending to 40 mg/kg. The study will enroll up to 24 patients, both ambulant and non-ambulant, between the ages of 7 to 21 at sites in the U.S., Canada, Australia and the European Union. The primary endpoint is safety, and secondary and exploratory endpoints include exon-skipping, dystrophin expression and tissue concentration. All patients will undergo a muscle biopsy at baseline and 12 weeks in Part A and baseline and 24 weeks in Part B. More information can be found on www.clinicaltrials.gov.

About SRP-5051

SRP-5051 uses Sarepta’s PPMO chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene. SRP-5051 is designed to bind to exon 51 of dystrophin pre-mRNA, resulting in the exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for the production of an internally truncated dystrophin protein. PPMO is Sarepta’s next-generation chemistry platform designed around a proprietary cell-penetrating peptide conjugated to the PMO backbone, intending to increase tissue penetration, increasing exon skipping and significantly increasing dystrophin production. Around 13% of DMD patients have mutations that make them amenable to skipping exon 51. If successful, the PPMO offers the potential for improved efficacy and less frequent dosing for patients.

What is exon skipping?

Mutations in the dystrophin gene are one cause of DMD. Most commonly, one or more exons (a portion of a gene) are missing, and the remaining exons don’t fit together correctly. (Think of a zipper that doesn’t work properly because teeth are missing.)

Because of this error, cells cannot make the dystrophin protein that muscles need to work properly. Without it, muscle cells become damaged and, over time, are replaced with scar tissue and fat.

To fix the broken genetic machinery, scientists are developing drugs that skip over parts containing missing or defective exons. In this way, the machinery can produce a less imperfect dystrophin protein, improving muscle function in children with exon mutations. > Pipeline exon-skipping

About eteplirsen (EXONDYS 51®)

This treatment uses a specific exon-skipping technique to jump over a portion of genetic machinery that does not produce dystrophin in children with DMD. More specifically, this injectable drug triggers the skipping of exon 51, which occurs in 13% of children with DMD. It aims to restore the machinery’s ability to read genetic code to produce a shortened form of dystrophin that works in some children with DMD. The production of this shortened form of dystrophin may delay muscle degeneration and the progression of this devastating, rare disease in some children.

In September 2016, the U.S. FDA granted unprecedented, accelerated marketing approval to eteplirsen to treat children with DMD who are amenable to exon 51 skipping. However, since clinical benefit has not been established, continued approval depends on whether the outcome of ongoing clinical trials can confirm its benefits in patients with DMD.

What about Canada?

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

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 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 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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The power of giving back

Giving Tuesday – the global day of giving

Join us for the 8th annual Giving Tuesday on December 1rst, 2020!

GivingTuesday is a global day of giving that happens each year after Black Friday and Cyber Monday. It’s a time when Canadians, charities and businesses come together to celebrate giving and participate in activities that support charities and non-profits. There is no “right” way to participate as long as it supports generosity and giving. Donate, volunteer time, help a neighbour, or spread the word.

GivingTuesday was started in Canada by a group of organizations, including GIV3CanadaHelps.org, and now includes over 6,500 partners. GivingTuesday was originally started in the US in 2012 by the NYC 92Y and several other community organizations.

 

Make a donation to La Force DMD here 

 

What was achieved in 2020?

The seventh annual GivingTuesday in Canada exceeded all expectations. Over 7,000 partners came together, and millions of Canadians joined in, creating national awareness, recognition and a massive impact on donations (+ 1247% at CanadaHelps since 2012) and other forms of giving.

 

What is GivingTuesday?

After Black Friday and Cyber Monday … imagine a day dedicated to giving back, around the world, across Canada and in our community. Black Friday kicks off the holiday shopping season; GivingTuesday ( December 1st, 2020) marks the giving season’s opening day. Visit www.givingtuesday.ca for more information.

 

Who is involved?

In Canada, GivingTuesday is an initiative of CanadaHelps and The GIV3 Foundation and 15 founding partners. They have been joined by thousands of Canadian charities, businesses and communities in a collective call to all Canadians to support charities of their choice. GivingTuesday was started in 2012 in the USA by the UN Foundation and the 92nd Street Y. The movement now includes more than 150 countries.

 

2019 Highlights

“Around the world, #GivingTuesday is a grassroots movement that illustrates the impact we can have when we all pull together. The investments we make—in both time and funding—can help solve the urgent problems of today and will make the next generation stronger. “ – President Barack Obama

 

Help someone afflicted with Duchenne muscular dystrophy (DMD)

What is Duchenne? It’s a degenerative muscle disease, afflicting mostly young boys 1-3500. It’s a fatal disease with no cure, taking muscle strength away and leaving young adults in a wheelchair and premature death in their late twenties. Many treatments are on the horizon, but we need your help to raise awareness and funds because there is no time to lose people afflicted with DMD. Our organization raises funds for promising research and raises awareness to have a unified DMD community across Canada to quickly access new treatment.

 

How to contribute to our cause:

There is no small amount!

Our organization aims to unite the DMD community to raise awareness around a common objective: providing access to new treatments as fast as possible and participating in the funding of promising research projects. We also raise funds for two promising research-based in Canada.

 

Make a donation to La Force DMD here

 

Other ways to support us:

  • Organize a fundraiser or a sporting event
  • Buy our promotional items to make gifts.
  • Share our stories, video and article.
  • Display our colours during your outings and events.

The development of edasalonexent will be stopped

Catabasis Pharmaceuticals announces top-line results for the phase 3 PolarisDMD trial of edasalonexent in Duchenne muscular dystrophy.

 

PolarisDMD Trial Did Not Achieve Primary or Secondary Endpoints – The development of edasalonexent will be stopped.

Original Press release BOSTON, MA, OCTOBER 26, 2020

 

Catabasis announced that the Phase 3 PolarisDMD trial of edasalonexent in Duchenne muscular dystrophy (DMD) did not meet the primary endpoint, a change from baseline in the North Star Ambulatory Assessment (NSAA) over one year of edasalonexent compared to placebo. The secondary endpoint timed function tests (time to stand, 10-meter walk/run and 4-stair climb) also did not show statistically significant improvements. Edasalonexent was observed to be generally safe and well-tolerated in this trial. Catabasis is stopping activities related to the development of edasalonexent, including the ongoing GalaxyDMD open-label extension trial. The Company plans to work with external advisors to explore and evaluate strategic options in the future.

 

Jill C. Milne, Ph.D., Chief Executive Officer of Catabasis – “We are deeply saddened and disappointed by the results of our Phase 3 PolarisDMD trial. I want to sincerely thank all of the boys, their families and caregivers, investigators and the trial sites that participated in and enabled this program. The entire Catabasis team has worked tirelessly to find a treatment for this progressive disease. We hope that our data and work to date can be used to benefit ongoing and future research in DMD.”

 

The Phase 3 trial was a one-year placebo-controlled trial designed to evaluate the safety and efficacy of edasalonexent in boys ages 4-7 (up to 8th birthday) with DMD. The global trial enrolled 131 boys across eight countries, with any mutation type, who were not on steroids. Edasalonexent was well-tolerated, consistent with the safety profile seen to date. The majority of adverse events were mild in nature, and the most common treatment-related adverse events were diarrhea, vomiting, abdominal pain and rash. There were no treatment-related serious adverse events and no dose reductions. The global COVID-19 pandemic had no meaningful impact on the trial or its results. Data from the PolarisDMD trial will be further analyzed and are expected to be presented at an upcoming scientific conference and published.

 

Pat Furlong, Founding President and Chief Executive Officer of Parent Project Muscular Dystrophy (PPMD) – “These results are disheartening for the Duchenne community, and specifically for the boys who participated in this trial and their families. However, the results contribute to the natural history data of Duchenne and add to the knowledge base that will one day produce a foundational, long-term therapy for this disease. The continued advancement of research and the development of possible treatment options will remain of critical importance to our community. We appreciate Catabasis’ efforts and commitment to every family that is or has ever been affected by Duchenne.”

 

What is Edasalonexent?

Edasalonexent (CAT-1004 is being developed as a potential foundational disease-modifying therapy for all patients affected by DMD, regardless of their underlying mutation. It is an investigational oral small molecule. Edasalonexent inhibits NF-kB, a protein activated by DMD and drives inflammation and fibrosis, muscle degeneration and suppresses muscle regeneration. By inhibiting NF-kB, edasalonexent can decrease inflammation and fibrosis, promote muscle regeneration, and slow disease progression. Edasalonexent was designed as a stand-alone therapy and may also enhance the efficacy of dystrophin targeted therapies.

 

About Catabasis

The mission of Catabasis Pharmaceuticals is to bring hope and life-changing therapies to patients and their families.

  • Watch this video recorded in November 2016; Dr. Joanne Donovan answers our questions about edasalonexent (CAT-1004)
  • CatabasisPharma on FacebookTwitter and Instagram if you are interested in the latest updates

 

About La Force DMD

The Force’s mission is to unite the DMD community to raise awareness around a common objective: providing access to new treatments as fast as possible and participating in the funding of promising research projects. Where access to treatments for rare diseases is concerned, it is essential that our community be strong: each member must be an active spokesperson who helps raise awareness for DMD among the general public and the challenges associated with access to treatment.

Catabasis would like to sincerely thank everyone who participated in and enabled the edasalonexent program. Read more here.

Santhera to discontinue Phase 3 SIDEROS study

Santhera to discontinue Phase 3 SIDEROS study and development of Puldysa® in Duchenne Muscular Dystrophy (DMD) and focus on vamorolone.

Original Press Release > Pratteln, Switzerland, October 6, 2020

Santhera Pharmaceuticals announces the discontinuation of its Phase 3 SIDEROS study with Puldysa® (idebenone) in patients with Duchenne muscular dystrophy (DMD) who are in respiratory decline and receive concomitant glucocorticoid treatment. Data from an interim analysis conducted by the independent Data and Safety Monitoring Board (DSMB) concluded that the study was unlikely to meet its primary endpoint. Consequently, Santhera will discontinue the study, withdraw the European marketing authorization application and end the global development program for Puldysa. The Company intends to initiate a restructuring plan to retain key functions for bringing DMD drug candidate vamorolone to patients and execute on its other pipeline programs.

Based on the now completed interim analysis tested for efficacy, the DSMB has recommended the SIDEROS study be discontinued due to futility. The interim analysis was based on the study’s primary endpoint, the change of forced vital capacity % predicted (FVC%p) from baseline to 18 months of treatment. The outcome revealed that the probability of reaching the primary endpoint at the end of the study is too small to merit the study’s continuation. There were no safety concerns noted by the DSMB.

Santhera will stop the SIDEROS trial.

Santhera will stop the SIDEROS trial (including extension), and participants who are enrolled in the study will discontinue study medication and complete the study’s follow-up evaluations. Furthermore, following up on the recommendation from the DSMB, Santhera will discuss the impact of ending the SIDEROS study on ongoing expanded access programs with the corresponding regulatory bodies.

 

Dario Eklund, Chief Executive Officer of Santhera “We would like to thank the patients and the families, as well as investigators and medical professionals, who participated in the SIDEROS study. Without their contributions, we would not be able to advance DMD research. While this is obviously not the outcome we expected, all our efforts in DMD will now be focused on progressing the promising drug candidate vamorolone which we recently licensed from ReveraGen to its next inflection point, the readout of 6-month topline data from the pivotal VISION-DMD study planned for the second quarter of 2021.”

 

In connection with this decision, Santhera intends to start a restructuring process, aligning its operations to focus on progressing vamorolone for DMD, lonodelestat for cystic fibrosis and other lung diseases discovery-stage gene therapy approach for congenital muscular dystrophy.

About SIDEROS

SIDEROS was a clinical trial in DMD, a double-blind randomized placebo-controlled Phase 3 study evaluating the efficacy of idebenone in delaying the loss of respiratory function in patients with DMD. Patients on any stable glucocorticoid treatment scheme and irrespective of the underlying dystrophin mutation or ambulatory status were randomized to receive oral idebenone (900 mg/day three times a day) or placebo for 18 months. The trial’s primary endpoint estimates the treatment difference in FVC%p (forced vital capacity % predicted). Read more about Idebenone.

About Santhera

Santhera Pharmaceuticals is a Swiss specialty pharmaceutical company focused on developing and commercializing innovative medicines for rare neuromuscular and pulmonary diseases with a high unmet medical need. Santhera has an exclusive license for all indications worldwide to vamorolone, a first-in-class anti-inflammatory drug candidate with a novel mode of action, currently investigated in a pivotal study in patients with DMD as an alternative to standard corticosteroids. The clinical-stage pipeline also includes lonodelestat (POL6014) to treat cystic fibrosis (CF) and other neutrophilic pulmonary diseases and omigapil and an exploratory gene therapy approach targeting congenital muscular dystrophies. Santhera out-licensed ex-North American rights to its first approved product, Raxone® (idebenone), to treat Leber’s hereditary optic neuropathy (LHON) to Chiesi Group. For further information, please visit www.santhera.com.  La Force DMD Blog /worldwide rights of vamorolone for DMD

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Pfizer receives FDA fast track designation for DMD gene therapy

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

Official press release > NEW YORK–(BUSINESS WIRE)

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

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

 

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

 

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

 

About PF-06939926

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

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

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

About Pfizer Rare Disease

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

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

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

Interesting links

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

La Force DMD / Press release from Pfizer about gene therapy

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Sustained functional improvement with micro-dystrophin gene treatment

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

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

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

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

 

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

 

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

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

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

About SRP-9001

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

About Duchenne Muscular Dystrophy

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

About Sarepta Therapeutics

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

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

The North Star Ambulatory Assessment (NSAA)

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

Catabasis Newsletter – Communicating clinical trial results

La Force is happy to share the latest edition of the Catabasis Connection newsletter – Communicating clinical trial results.

Catabasis understands the importance of clearly communicating clinical trial results with the Duchenne community. As they are getting prepared for the planned release of top-line results from their Phase 3 PolarisDMD trial in Q4 of this year, they are sharing in advance their plans for how those results will be communicated. As a public, pre-commercial stage company, Catabasis is making every effort to balance its reporting obligations and restrictions with the desire to inform the Duchenne community of the trial results quickly, efficiently, and in easily accessible ways. Here are their plans:

  • They will share top-line results in their newsletter and a press release simultaneously. You can sign up here.
  • They will be sharing both the newsletter and press releases on their social media. You can follow them on social media > FacebookTwitter and Instagram.
  • They will host a webinar for the Duchenne community in conjunction with PPMD within a couple of days of the release of the top-line results. The webinar will include a Q&A portion where you can ask questions.
  • Families participating in the Phase 3 PolarisDMD trial can hear about the next steps directly from their trial site personnel.

About Edalasolexent

Edasalonexent is an orally-administered small molecule designed to inhibit NF-kB. Activated NF-kB is a crucial link between the lack of dystrophin and resulting manifestation and progression of Duchenne. By inhibiting NF-kB in Duchenne, edasalonexent can limit muscle degeneration, promote muscle regeneration, and reduce inflammation and fibrosis. Edasalonexent is being developed as a monotherapy and for use with other therapies, such as exon-skipping. We believe that based on its mechanism of action, edasalonexent has the potential for use with different approaches in development, such as gene therapy. The Phase 3 PolarisDMD trial and GalaxyDMD open-label extension trial are both ongoing. Top-line results are expected in the fourth quarter of 2020.

About Catabasis

The mission of Catabasis Pharmaceuticals is to bring hope and life-changing therapies to patients and their families. There lead program is edasalonexent, an NF-kB inhibitor in Phase 3 development for the treatment of Duchenne muscular dystrophy. For more information on edasalonexent and the Phase 3 trial, please visit www.catabasis.com.

About La Force DMD

The Force’s mission is to unite the DMD community to raise awareness around a common objective: that of providing access to new treatments as fast as possible and to participate in the funding of promising research projects. Where access to treatments for rare diseases is concerned, it is essential that our community be strong: each member must be an active spokesperson who helps raise awareness for DMD among the general public and the challenges associated with access to treatment.

 

Edasalonexent is an investigational drug that is not yet approved in any territory.

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Worldwide rights of Vamorolone for DMD

Santhera exercises option to obtain worldwide rights of Vamorolone for Duchenne muscular dystrophy (DMD) and All Other Indications

La Force is happy to share this press release provided by Santhera Pharmaceuticals > Pratteln, Switzerland, and Rockville, MD, USA, September 2, 2020

 

Santhera Pharmaceuticals announces that it has signed agreements with Idorsia and ReveraGen BioPharma Inc., making Santhera a direct license holder of vamorolone. Under the agreements, Santhera has obtained an exclusive license from ReveraGen, the originator of vamorolone, for all indications worldwide. The agreements create additional value for Santhera through the transfer of rights for the previously excluded markets Japan and South Korea, the right to grant sublicenses and a share in the expected Priority Review Voucher. Vamorolone, a first-in-class anti-inflammatory drug candidate with a novel mode of action, is currently being investigated in the pivotal Phase 2b VISION-DMD study in patients with Duchenne muscular dystrophy (DMD) by originator ReveraGen and completion of study enrollment is expected shortly.

 

Quickly

  • The license gives Santhera worldwide rights to vamorolone, now also including the major markets Japan and South Korea, and paves the way for partnering in additional indications
  • Agreements with Idorsia and ReveraGen give Santhera immediate control over vamorolone and defer milestone-related payments
  • The transaction establishes Santhera as a leading company in rare neuromuscular diseases with two late-stage assets addressing the medical need of DMD patients from early to late disease stages

 

Dario Eklund, Chief Executive Officer of Santhera –  “We are excited about the license transfer of vamorolone to Santhera. Our decision to exercise the option now has been driven by a combination of factors including the availability of encouraging clinical efficacy and safety data with vamorolone, enhanced deal terms and the ability to gain full control over the asset. We look forward to contributing our significant expertise to advancing vamorolone in DMD and exploring additional business development opportunities. We believe that having two promising, complementary, late-stage assets for DMD in our pipeline will enable increased access to potentially transformative treatments for a wider patient population. We are grateful to Idorsia, our anchor shareholder, for enabling early access to the license, highlighting its confidence in Santhera as the best-suited company to bring vamorolone to patients.”

 

Eric Hoffman, Ph.D., Vice President of Research of ReveraGen BioPharma –  “We are delighted about the revised contractual arrangement and being able to work directly with Santhera as the licensee for vamorolone. Santhera’s experience in both development of DMD drug candidates and the commercialization of a rare disease product positions it well to bring vamorolone to patients. Our work to date clearly shows that vamorolone not only holds the potential to become a new standard of care for patients with DMD but also could benefit patients in a number of other inflammatory diseases.”

 

With Puldysa® and vamorolone, Santhera is building a complementary DMD product portfolio.

Vamorolone is in development for young DMD patients requiring an anti-inflammatory, muscle strengthening treatment before the onset of respiratory function decline. Based on the cumulative knowledge obtained from extensive non-clinical studies and Phase 1 and Phase 2a clinical studies with vamorolone, ReveraGen is currently conducting the pivotal Phase 2b VISION-DMD trial and anticipates full study enrollment shortly. Subject to positive results of the first 6-month treatment period, now expected in the second quarter of 2021 due to delays caused by the Covid-19 pandemic, this would pave the way for regulatory submission to the US FDA in the fourth quarter of 2021.

Puldysa (idebenone) for patients with DMD in respiratory function decline who are not taking glucocorticoids is currently under regulatory review in Europe for which Santhera anticipates a CHMP opinion in the fourth quarter of 2020. The Company expects the combination of vamorolone and Puldysa to address the medical needs of DMD patients, from early to late disease stages, irrespective of age, underlying dystrophin mutation or ambulatory status. 

Vamorolone and Puldysa have been granted Orphan Drug status in the US and Europe, Fast Track and Rare Pediatric Disease designations by the US FDA and Promising Innovative Medicine (PIM) status by the UK MHRA. In the UK, Puldysa is available to patients through the Early Access to Medicines Scheme (EAMS).

 

About Vamorolone

Vamorolone is a first-in-class anti-inflammatory drug candidate with a novel mode of action Vamorolone is a first-in-class drug candidate that binds to the same receptors as corticosteroids but modifies the downstream activity of the receptors. This has the potential to ‘dissociate’ efficacy from typical steroid safety concerns and, therefore, could emerge as a valuable alternative to corticosteroids, the current standard of care in children and adolescent patients with DMD. There is a clear unmet medical need in this patient group as high dose corticosteroids have significant systemic side effects that detract from the patient’s quality of life. Vamorolone is being developed by US-based ReveraGen BioPharma Inc. with participation in funding and design of studies by several international non-profit foundations, the US National Institutes of Health, the US Department of Defense and the European Commission’s Horizon 2020 program.

 

About Santhera

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

 

About ReveraGen BioPharma

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

 

More links

Virtual marathon for DMD

Learning that your son has Duchenne muscular dystrophy (DMD) is watching your child lose his muscular ability month after month. This is Jean-Philippe Morand’s reality: his son Victor is stricken with Duchenne muscular dystrophy. In adversity, some men go beyond their limits, and this is what Jean-Philippe will do again on Saturday, September 12, by participating in the 124th Boston Marathon in the company of his two sons Victor and Vincent. They are on a mission to raise awareness about Duchenne. Every effort to raise awareness about this rare and devastating disease will help us facilitate access to new treatments. Victor will accompany Jean-Philippe in a racing chair.

 

Jean-Philippe Morand – « For 5 years since I started running, in order to bring this sport to life for my son, Victor, who has Duchenne muscular dystrophy. It must be said that I am more of a cyclist at the base! Several races and marathons including the one in May 2019 where I qualified for Boston 2020. I had to go run it alone in April 2020 because Victor is not of the required age, but the Boston edition has been converted into an edition virtual and will be held on September 12th.
I will therefore have the pleasure of running the 124th edition of the Boston Marathon with Victor on September 12th. The Clan Morand is Victor and me, but also Vincent who will be my official “rabbit pacer” on the bike.
I invite you to come and cheer us on Saturday, September 12th, come run or roll km with us. »

 

124th Boston Marathon to be Held Virtually

The Boston Athletic Association (BAA) has announced that the 124th Boston Marathon will be held as a virtual event, following Boston Mayor Martin Walsh’s cancellation of the marathon as a mass participation road running event due to the COVID-19 pandemic. The virtual Boston Marathon will be complemented by a series of virtual events throughout the second week of September. [ Read more here ]

 

Victor was diagnosed with Duchenne

DMD is an incurable and 100% fatal disease. Duchenne muscular dystrophy is a rare genetic disorder that mainly affects boys. The progression of DMD is unforgiving: the body’s muscles gradually weaken, leaving the boys in a wheelchair at the age of 12, with a life expectancy of 20 to 30 years. Today there is hope for DMD, and several new treatments are on the horizon.

 

Raising funds and awareness to access new treatments

Within the next 5 to 10 years (or even before then), some new treatment options should be on their way to completion. Now, treatments are approved in the US and Europe, but not yet available in Canada. Therefore, educating people about what Duchenne is and about access to new therapies is extremely important. It will help children like Victor access the latest treatments rapidly before the disease has evolved too much.

 

Please support them

There’s nothing better than a father’s courage to raise awareness about Duchenne muscular dystrophy. Today there is hope for DMD, and several new treatments are on the horizon. This hope motivates Jean-Philippe to go beyond his limits for his son, but what he does also benefit all children with DMD. Le Clan Morand invites you to donate $ 10 / KM run with them. [ here ]

The La Force DMD team is proud to support Jean-Philippe Morand and his family.

 

Other interesting articles

 

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FDA Acceptance of Casimersen

Sarepta Therapeutics Announces FDA Acceptance of Casimersen (SRP-4045) New Drug Application for Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 45

Original press release, CAMBRIDGE, Mass., Aug. 25, 2020 (GLOBE NEWSWIRE)

Quickly

  • FDA grants Priority Review Status and sets regulatory action date for February 25, 2021
  • FDA has indicated it does not currently plan to hold an advisory committee meeting to discuss the application
  • Received FDA’s conditional approval of AMONDYS 45™ as a brand name for casimersen
  • Casimersen has been studied for the treatment of exon 45 amenable patients, approximately eight percent of patients with Duchenne

About the FDA Acceptance of Casimersen

Sarepta Therapeutics, Inc. announced the U.S. Food and Drug Administration (FDA) has accepted the Company’s New Drug Application (NDA) seeking accelerated approval for casimersen (SRP-4045) and provided a regulatory action date of February 25, 2021. The FDA has indicated it does not currently plan to hold an advisory committee to discuss the application. In addition, the Company has received conditional approval of AMONDYS 45 as the brand name for casimersen. 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 dystrophin gene.

The Company submitted its NDA filing in June 2020 and requested priority review, which the FDA granted. The NDA included 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 the efficacy and safety of casimersen in patients amenable to skipping exons 45. 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.

Doug Ingram, president and chief executive officer, Sarepta Therapeutics – “The FDA’s acceptance of our NDA for casimersen is an important step toward our goal of rapidly bringing therapies to patients living with Duchenne muscular dystrophy. If it is approved, casimersen, our third exon-skipping medicine in our PMO RNA-based platform, will offer treatment to the 8% of Duchenne patients who are amenable to exon 45 skipping.”

About Casimersen

Casimersen uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 45 of the Duchenne 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 for the production of an internally truncated dystrophin protein. Read more here.

About the ESSENCE Study

The ESSENCE study is a double-blind, placebo-controlled, multi-center Phase 3 study evaluating the efficacy and safety of casimersen (SRP-4045) and golodirsen (SRP-4053, approved as VYONDYS 53™). Eligible patients with out-of-frame deletion mutations amenable to exon 45 or 53 skippings are randomized to receive once-weekly intravenous (IV) infusions of 30 mg/kg of SRP-4045 or 30 mg/kg of SRP-4053, respectively (combined-active group) or placebo for up to 96 weeks. This is followed by an open-label extension period in which all patients will receive open-label active treatment for 48 weeks, up to week 144 of the study.

Clinical efficacy is being assessed at regularly scheduled study visits, including functional tests such as the six-minute walk test (6MWT). All patients undergo a muscle biopsy at baseline and will undergo a second muscle biopsy either at week 48 or week 96.

Safety is being assessed through the collection of adverse events, laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations throughout the study.

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.

More about DMD

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

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