The global day of giving

Giving Tuesday – the global day of giving

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 marks the giving season’s opening day. Visit www.givingtuesday.ca for more information. Canada, join us for the 9th annual GivingTuesday on November 30, 2021.

 

What is GivingTuesday?

GivingTuesday is the world’s largest generosity movement. It was created in 2012 as a simple idea: a day that encourages people to do good: make someone smile, help a neighbour or stranger, show up for an issue you care about or give some of what you have to those in need. Over the past nine years, it has since grown into a global movement, unleashing the power of people and organizations to transform their communities and the world. GivingTuesday is a time when Canadians, charities, and businesses come together to celebrate giving and participate in activities that support charities and non-profits; to thank, help, give, show kindness, and share what they have with those in need. Every act of generosity counts. Everybody has something to give.

 

– President Barack Obama – “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.“

 

DID YOU KNOW? In 2020 it is estimated that over 6 million Canadians did something to support their favourite causes for GivingTuesday!

Donate 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.

La Force DMD est partenaire de cette journée (visitez la page ici).

 

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 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 funding promising research projects. We also raise funds for two promising research-based in Canada.

 

Donate 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.

 

Links

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EMBARK, gene therapy for the treatment of DMD

Sarepta Therapeutics announces initiation of EMBARK, a global p0ivotal study of SRP-9001, gene therapy for the treatment of DMD (Duchenne Muscular Dystrophy)

Original press release > CAMBRIDGE, Mass., Oct. 04, 2021 (GLOBE NEWSWIRE)

Sarepta Therapeutics, Inc., the leader in precision genetic medicine for rare diseases, today announced the initiation, in partnership with Roche, in the U.S. and countries around the world, of study SRP-9001-301, also known as EMBARK, a pivotal study of SRP-9001 (rAAVrh74.MHCK7.micro-dystrophin) for the treatment of Duchenne muscular dystrophy. SRP-9001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein.

 

Doug Ingram, president and chief executive officer, Sarepta – “We are delighted to announce the initiation of EMBARK, representing the first pivotal double-blind gene therapy trial in Duchenne which will be initiated in the US, Europe and Asia.”

 

“The initiation of EMBARK represents the culmination of enormous effort and success from a research, development and manufacturing perspective and is an extraordinarily important moment for the patient community and a leap forward in our effort to change the course of Duchenne. In addition to our team, our investigators and the families who have participated in our trials, I want to thank the professionals within FDA’s Office of Tissues and Advanced Therapies for their collaborative guidance and insight as we finalized our EMBARK study and advance the SRP-9001 program. We look forward to sharing the particulars of EMBARK and additional functional data from our prior studies in our upcoming ‘Micro-dystrophin Day’.”

 

Webcast live

The Company will host an SRP-9001 Micro-dystrophin R&D Day on Monday, Oct. 11, 2021, at 8:30 am Eastern Time.

The presentation will be webcast live under the investor relations section of Sarepta’s website here, and slides will be archived there following the call for one year. Please connect to Sarepta’s website several minutes before the start of the broadcast to ensure adequate time for any software download that may be necessary. The conference call may be accessed by dialling (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 3878397. Please specify to the operator that you would like to join the “SRP-9001 Micro-dystrophin R&D Day” call.

 

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

SRP-9001 is an investigational gene transfer therapy intended to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. Sarepta is responsible for global development and manufacturing for SRP-9001 and plans to commercialize SRP-9001 in the United States upon receiving FDA approval. In December 2019, Roche partnered with Sarepta to combine Roche’s global reach, commercial presence and regulatory expertise with Sarepta’s gene therapy candidate for Duchenne to accelerate access to SRP-9001 for patients 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.

 

Community letter from Sarepta

 

October 4, 2021,

Dear Duchenne Community,

Today, Sarepta Therapeutics announced the initiation, in partnership with Roche, in the United States, and countries around the world, of study SRP-9001-301, also known as EMBARK, a pivotal study of SRP-9001 (rAAVrh74.MHCK7. micro-dystrophin) for the treatment of Duchenne muscular dystrophy. SRP-9001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the microdystrophin protein.

Initiating a clinical trial means that the study sponsor(s) and clinical trial sites take the necessary steps required to enable dosing of the investigational therapy. These initiating steps happen prior to the first patient being recruited into a study.

We have received many inquiries in the past months, and we recognize the interest and urgency expressed by the Duchenne community. Parent Project Muscular Dystrophy (PPMD) has invited us to share details of the EMBARK clinical trial on a community webinar, which we are targeting for the week of October 11th. Please stay tuned for an announcement from PPMD.

Many individuals with Duchenne, families, and Patient Advocacy Organizations have contributed time and effort to support early studies of this investigational therapy. We thank you for your dedication, without which this milestone in therapeutic development efforts would not be possible.

With our kind regards,

Siobhan Fitzgerald

 

A link to the community letter may be found here.

 

About Sarepta

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

More interesting links

Source

Sarepta Therapeutics, Inc.

 

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Part B of MOMENTUM study of SRP-5051 in patients with DMD

Sarepta Therapeutics to initiate Part B of MOMENTUM study of SRP-5051 in patients with Duchenne muscular dystrophy (DMD) amenable to Exon 51 skipping following positive interactions with FDA

Original press release CAMBRIDGE, Mass., Sept. 27, 2021 (GLOBE NEWSWIRE)

  • Company Anticipates Part B of MOMENTUM to Serve as Pivotal Study for SRP-5051 and to Seek Accelerated Approval if Successful
  • Ambulatory and Non-Ambulatory Patients Between the Ages of 7 to 21 Will Be Eligible to Enroll in Part B of MOMENTUM

Sarepta Therapeutics, Inc., the leader in precision genetic medicine for rare diseases, today announced that following positive interactions with the U.S. Food and Drug Administration (FDA), the Company plans to initiate Part B of the MOMENTUM study (Study 5051-201), in the fourth quarter. MOMENTUM is a global trial investigating the use of SRP-5051, the Company’s next-generation peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO), to treat patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping.

The study will enroll 20-40 patients between ages 7 to 21 amenable to exon 51 skipping who are naïve to SRP-5051. Additionally, those previously dosed in Study 5051-201, Part A or Study 5051-102 who meet the entrance criteria will be eligible to participate. Both ambulatory and non-ambulatory patients are eligible for participation. The Company will submit the protocol in the next week.

 

Doug Ingram, Sarepta’s president and chief executive officer – “If proven safe and as efficacious as our initial data suggest it may be, SRP-5051 could be the first in a host of transformative therapies from our next-generation PPMO platform to treat and improve the lives of children living with Duchenne muscular dystrophy. In addition to the fantastic work of our team, and the dedication of Duchenne families and the program’s investigators, I would like to thank FDA’s Division of Neurology I for their diligence and thoughtful advice and input, without which we would not be able to commence Part B of the MOMEMTUM study ahead of schedule.”

 

 

About MOMENTUM (Study SRP-5051-201)

MOMENTUM is a multi-arm, ascending dose study of SRP-5051, infused monthly and will assess dystrophin protein level in skeletal muscle tissue following SRP-5051 treatment. The study will enroll both ambulant and non-ambulant patients between the ages of 7 to 21 at sites in the U.S., Canada, Australia, and the European Union. The study will also assess safety and tolerability.

In May of this year, the Company announced results from Part A of the MOMENTUM study showing that after 12 weeks, 30 mg/kg of SRP-5051 dosed monthly resulted in 18 times the exon skipping and eight times the dystrophin production as eteplirsen, dosed weekly for 24 weeks.

Reversible hypomagnesemia was identified in patients taking SRP-5051. The protocol for Part B of MOMENTUM will include magnesium supplementation and monitoring of magnesium levels.

 

About SRP-5051

SRP-5051 is an investigational agent using 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 excluding 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.

About Duchenne Muscular Dystrophy (DMD)

DMD is an X-linked rare degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 – 5,000 male births worldwide. DMD is a devastating and incurable muscle-wasting disease associated with specific gene errors that code for dystrophin. This protein plays a critical structural role in muscle fibre function. Progressive muscle weakness in the lower limbs spreads to the arms, neck, and other body areas. The condition is universally fatal, and death usually occurs before 30 due to respiratory or cardiac failure.

About EXONDYS 51

EXONDYS 51 (eteplirsen) uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 51 of dystrophin pre-mRNA, resulting in “skipping” 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.

EXONDYS 51 is indicated for the treatment of Duchenne muscular dystrophy in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping.

This indication is approved under accelerated approval based on increased dystrophin production in skeletal muscle observed in some patients treated with EXONDYS 51. Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials.

EXONDYS 51 has met the full statutory standards for safety and effectiveness and, as such, is not considered investigational or experimental.

 

 

 

Source: Sarepta Therapeutics, Inc.

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World Duchenne Awareness Day 2021

September 7 is World Duchenne Awareness Day. On this day, we raise awareness for Duchenne and Becker muscular dystrophy (DMD and BMD) around the globe.

An initiative coordinated by the World Duchenne Organization. Press release here

 

Produced by the World Duchenne Organization

The official promo video is initiated and produced by the World Duchenne Organization and coordinated by Nicoletta Madia. “Words are important. Words can help make a difference. This is the theme that emerges from the video for World Duchenne Awareness Day 2021. The video shows various portraits of people living with Duchenne in daily life. Three words are highlighted that means a lot to people living with Duchenne MD.”

  • Duchenne encompasses what it means to live with this pathology and the commitment of research and clinic in this field.
  • Community includes thousands of people globally committed to changing the quality of life of people living with this disease.
  • Awareness encompasses the importance of informing about this rare condition globally by reaching the greatest number of people. An objective that is at the center of this day and for which the World Duchenne Organization asks everyone to spread the word.

Video from World Duchenne Organization

 

Adult men living with Duchenne

The number of adult men living with Duchenne Muscular Dystrophy (DMD) is growing bigger every year. This can largely be attributed to better medical care, such as supportive ventilation and the use of preventive (cardiac) medication. These men want and deserve to live their lives to the fullest. This means they have the right to receive adequate care, have opportunities to live independently and participate in society.

However, the medical profession and society are often not ready to facilitate this. While knowledge of optimal care for pediatric patients has expanded considerably and the organization of care has improved for this group, there are no care guidelines so far for adult men.

Read more on their website here.

 

An online event on Adult Life & Duchenne

The World Duchenne Organization is organizing an online educational event on Adult Life & Duchenne. The free event on September 7 will be accessible for everybody via Zoom and is available with live Spanish interpretation.

 

Raising awareness

The official hashtag for the awareness-raising campaign is #spreadtheword. Everyone is encouraged to share this video with their friends and family to raise awareness for Duchenne and Becker muscular dystrophy.

 

About DMD/BMD

Duchenne and Becker muscular dystrophy (DMD and BMD) are two muscle-wasting conditions. Mutations in the dystrophin gene cause both. A certain part of the DNA is missing, duplicated, or changed, so the code cannot be read correctly by the body. This leads to the absence of the dystrophin protein, which plays an essential role in the muscle and brain. Without dystrophin, muscle cells easily get damaged, leading to a loss of these cells and, thereby, muscle function.

This can also happen in the brain, where dystrophin is missing as well. Where Duchenne individuals have a complete lack of dystrophin, people affected with Becker muscular dystrophy have lower levels or a shorter version of this protein.

 

Key facts

  • Duchenne and Becker muscular dystrophy are rare genetic diseases defined by muscle weakness
  • The dystrophin protein cannot be made due to an error on the X chromosome
  • Currently, there is no cure available for this fatal disease
  • Each year, 1 in 5.000 newborn boys receive the diagnosis of DMD
  • Lack of awareness contributes to an average delay of diagnosis of 2,5 years

 

Useful links

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ENDEAVOR, gene therapy for DMD

Sarepta Therapeutics’ investigational gene therapy for the treatment of Duchenne muscular dystrophy, SRP-9001, demonstrates robust expression and consistent safety profile using Sarepta’s commercial process material.

 

  • The first 11 participants enrolled in Study 9001-103 ENDEAVOR showed robust transduction, delivering mean vector genome copies of 3.87 per nucleus.
  • Treated patients achieved mean micro-dystrophin expression levels of 55.4% of normal as measured by western blot.
  • Micro-dystrophin was properly localized to the muscle sarcolemma, with patients achieving a mean percentage of dystrophin positive fibres of 70.5% and intensity of micro-dystrophin expression of 116.9% of normal control measured by immunofluorescence (IF).
  • Safety profile consistent with prior studies and no new safety signals identified.

 

Original press release > CAMBRIDGE, Mass., May 18, 2021 (GLOBE NEWSWIRE)

Sarepta Therapeutics, Inc. announced positive 12-week expression and safety results from the first 11 participants enrolled in Study SRP-9001-103, an open-label study known as ENDEAVOR conducted in partnership with Roche. In results from the first clinical study using commercially representative material, SRP-9001 (rAAVrh74.MHCK7.micro-dystrophin) demonstrated robust expression of micro-dystrophin and no new safety signals from prior studies, supporting its potentially differentiated profile for the treatment of Duchenne muscular dystrophy. SRP-9001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein.

 

Doug Ingram, president and chief executive officer, Sarepta – “We are delighted by these seminal results from the ENDEAVOR Study, our first trial results with SRP-9001 made by our commercial-scale manufacturing process. These data show strong transduction of the micro-dystrophin gene, resulting in robust expression of the properly localized micro-dystrophin protein, and did so with no new or unexpected safety signals. In addition to characterizing and differentiating SRP-9001, these results confirm the extraordinary work done over the last two and a half years to build an at-scale gene therapy manufacturing process and corresponding analytics sufficient to meet the needs of the Duchenne population with what we believe will be a potentially life-changing therapy. Armed with these data, we will seek a meeting with the FDA with the goal of rapidly starting our registrational study.”

 

Observed results

In the open-label study, 20 participants between the ages of four and seven were treated with a single infusion of SRP-9001 at a dose of 1.33×1014 VG/kg. In muscle biopsies from the first 11 patients taken 12 weeks after treatment, the following results were observed:

  • All patients demonstrated robust transduction, with a mean micro-dystrophin expression of 55.4% normal, as measured by western blot.
  • Muscle dystrophin levels demonstrated a mean of 70.5% (baseline 12.8%) muscle fibres expressing micro-dystrophin at 12 weeks with a mean intensity at the sarcolemma of 116.9% (baseline 41.0%) compared to normal biopsies, as measured by immunofluorescence. Comparisons between baseline and post-treatment measures were statistically significant (p=0.001 for positive fibres and p=0.002 for intensity).
  • Mean vector genome copies per nucleus reached 3.87.

The safety profile of SRP-9001 observed in the first 11 participants in ENDEAVOR is consistent with the safety seen in earlier studies using clinical manufacturing process material. In line with previously reported clinical data, no clinically relevant complement activation was observed in these 11 patients. Two patients experienced serious adverse events (transaminase elevation in one patient and nausea and vomiting in a second patient) that fully resolved.

About SRP-9001-103 (ENDEAVOR)

Study SRP-9001-103 (Study 103) is an open-label clinical trial of SRP-9001 that has enrolled 20 participants with Duchenne muscular dystrophy between the ages of 4-7. Study 103 uses commercially representative SRP-9001, and the primary endpoint is the change from baseline in the quantity of micro-dystrophin protein expression measured by western blot at 12 weeks. Secondary outcome measures include change from baseline in micro-dystrophin expression fibre intensity measured by immunofluorescence (IF) and micro-dystrophin expression measured by IF percent dystrophin positive fibres at 12 weeks. Exploratory endpoints include the change in vector genome copies per nucleus, North Star Ambulatory Assessment (NSAA) and certain timed functional tests. Including the initial 12-week period, patients will be followed for a total of five years.

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

SRP-9001 is an investigational gene transfer therapy intended to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. Sarepta is responsible for global development and manufacturing for SRP-9001 and plans to commercialize SRP-9001 in the United States upon receiving FDA approval. In December 2019, Roche partnered with Sarepta to combine Roche’s global reach, commercial presence and regulatory expertise with Sarepta’s gene therapy candidate for Duchenne to accelerate access to SRP-9001 for patients 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 walking, climbing stairs or standing from a sitting position. As the disease progresses, muscle weakness in the lower limbs spreads to the arms 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 is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. They hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and they currently have more than 40 programs in various stages of development. Their multi-platform Precision Genetic Medicine Engine drives our vast pipeline in gene therapy, RNA and gene editing. For more information, please visit www.sarepta.com or follow them on TwitterLinkedInInstagram and Facebook.

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Positive clinical results from phase 2 MOMENTUM study

Sarepta Therapeutics reports positive clinical results from phase 2 MOMENTUM study of SRP-5051 in patients with Duchenne muscular dystrophy amenable to skipping exon 51

  • Results suggest a highly potent next-generation treatment that could offer greater efficacy with less frequent dosing.
  • SRP-5051 dosed monthly at 30 mg/kg delivered mean exon skipping of 10.79% and mean dystrophin expression of 6.55%, consistently higher than the other SRP-5051 dosing cohorts at 12 weeks and weekly eteplirsen at 24 weeks
  • Sarepta’s predictive model indicates that SRP-5051 at 30 mg/kg will achieve greater than 10% dystrophin with monthly chronic dosing.

Original press release > CAMBRIDGE, Mass., May 03, 2021 (GLOBE NEWSWIRE)

Sarepta Therapeutics, Inc. announced positive results from Part A of the MOMENTUM study (Study 5051-201), a global, Phase 2, multi-ascending dose clinical trial of SRP-5051, its next-generation peptide phosphorodiamidate morpholino oligomer (PPMO) treatment for patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping. In biopsies taken at a median of 12 weeks and after only three doses, results from Part A of the MOMENTUM study found that the 30 mg/kg of SRP-5051 dosed monthly resulted in 18 times the exon skipping and eight times the dystrophin production as eteplirsen, dosed weekly for 24 weeks. Exon-skipping and dystrophin production in the 30 mg/kg cohort were also consistently higher than the 20 mg/kg cohort of MOMENTUM. Hypomagnesemia was identified in patients taking SRP-5051. Cases have resolved with magnesium supplementation, and analysis of all available data indicates that the hypomagnesemia is monitorable and manageable. 

 

Doug Ingram, president and chief executive officer, Sarepta – “We are pleased to report strong, dose-dependent exon-skipping and dystrophin expression results with monthly dosing of SRP-5051 – in ambulant and non-ambulant patients. Even at an early time point of 12 weeks and after as few as only three doses, these data confirm the potential of Sarepta’s next-generation PPMO platform to be a step order improvement over our current PMO platform and to profoundly impact the course of Duchenne. While we saw exceptional expression after only a few initial doses, our models predict that we will exceed dystrophin expression levels of 10% of normal or greater over time with SRP-5051.We are excited to have chosen our target dose for further development. Part A of MOMENTUM is now complete and Sarepta will work with great urgency to discuss the results with regulatory agencies and gain their insights, including the development path to support accelerated approval of SRP-5051 in the United States.”

 

Adverse events

There were three serious, treatment-emergent adverse events in two patients in the 30 mg/kg cohort, including two cases of hypomagnesemia. The events were asymptomatic and have resolved with magnesium supplementation. Markers of kidney function have generally been normal and not shown any consistent relationship to hypomagnesemia. Predictive modelling for dystrophin accumulation that includes assumptions of known turnover of dystrophin in the muscle and analysis of data generated with the PPMO platform indicates that SRP-5051 at 30 mg/kg is likely to deliver greater than 10% dystrophin over time with monthly dosing. Full results will be presented at a future medical meeting.

About MOMENTUM (Study SRP-5051-201)

MOMENTUM is a multi-arm, ascending dose study designed to identify the maximum tolerated dose of SRP-5051, infused monthly. 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. More information can be found on www.clinicaltrials.gov. Read “Positive clinical results from MOMENTUM” here.

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.

About Duchenne Muscular Dystrophy

DMD is an X-linked rare degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 – 5,000 male births worldwide. A devastating and incurable muscle-wasting disease, DMD is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fibre function. Progressive muscle weakness in the lower limbs spreads to the arms, neck, and other body areas. The condition is universally fatal, and death usually occurs before 30 due to respiratory or cardiac failure.

About EXONDYS 51

EXONDYS 51 (eteplirsen) uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 51 of dystrophin pre-mRNA, resulting in “skipping” 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.EXONDYS 51 is indicated for the treatment of Duchenne muscular dystrophy in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in some patients treated with EXONDYS 51. Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials. EXONDYS 51 has met the full statutory standards for safety and effectiveness and is not considered investigational or experimental.

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

About Sarepta

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Genethon announces First Patient dosed in Clinical Trial

Genethon announces First Patient dosed in Clinical Trial of Investigational Gene therapy GNT004 for Duchenne Muscular Dystrophy.

Communiqué de presse original > Genethon

 

A first participant was dosed at I-Motion, the pediatric clinical trial platform for neuromuscular diseases located at Trousseau hospital in Paris, as part of the gene therapy trial in Duchenne muscular dystrophy (DMD) conducted by Genethon.

A young boy with Duchenne muscular dystrophy received a first dose of the investigational gene therapy GNT004. He was the first patient in an international phase I/II/III multicenter trial for which Genethon is the sponsor. The trial has been approved in France by the French National Agency for Medicines and Health Products Safety (ANSM) and in the UK by British Medicines & Healthcare products Regulatory Agency.

 

CEO Frédéric Revah – “Dosing this first patient is a step that is profoundly symbolic for Genethon. This trial is the culmination of 30 years of pioneering research by Genethon. It embodies the quality of the research conducted in our laboratories, in collaboration with high-performing international teams. Duchenne is a very challenging disease and while we are cautious, we are hopeful and proud that the technologies developed at Genethon are today becoming drug candidates that could change the future for patients suffering from Duchenne muscular dystrophy.”

 

Prof. Muntoni from the Dubowitz Neuromuscular Center (UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital (London, UK)), the principal investigator for the trial. – “There remains a tremendous unmet need for treatments to help individuals affected by DMD. We put high hopes in this novel candidate.”

 

About GNT004

The gene therapy (GNT 0004) is based on an adeno-associated virus (AAV) capsid and an optimized gene, a shortened version of the gene coding for dystrophin, the absent protein in patients with Duchenne muscular dystrophy. This micro-dystrophin, associated with a vector designed to be expressed in muscle tissues, was developed by Genethon in partnership with the teams of Prof. Dickson (University of London, Royal Holloway) and the Institute of Myology (Paris). It is now developed jointly in the clinical phase with Sarepta Therapeutics. In the video, Professor George Dickson answers our questions about gene therapy & exon-skipping drugs.

 

About the trial

This phase I/II/III gene therapy trial is a multicenter dose determination trial, followed by the randomized efficacy part of the trial, to assess the product’s efficacy versus placebo. After the one year following the treatment with a placebo, the crossover is planned to allow all participants to benefit from the treatment potentially. The trial uses a single intravenous injection of GNT 0004. The trial aims to enroll boys aged 6 to 10 suffering from Duchenne muscular dystrophy who can still walk. The trial was approved in France, in the UK, and submissions are ongoing in the USA and Israel. The main criterion for evaluating efficacy is the change on the North Star Ambulatory Assessment (NSAA) score at one year. The NSAA is a validated 17-item rating scale used to measure functional motor abilities in ambulant children.

 

About Généthon

Genethon was created in 1990 by the AFM-Telethon with donations from the first Telethon. The stakes at that stage were huge: deciphering the human genome, tracking down the genes responsible for genetic diseases and using this knowledge to make innovative drugs. Thirty years later, the first gene therapy drug, to which Genethon contributed, has obtained marketing authorization in the United States, Europe and Japan for spinal muscular atrophy. Also, 10 products resulting from Genethon research and developed alone or in collaboration are today in clinical trials for rare diseases involving eyesight, the liver, blood, the immune system and the muscles. A further 8 products are in the preparation phase for clinical trials over the next five years. Follow them on Twitter and LinkedIn.

Pamrevlumab for the treatment of DMD

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

 

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

 

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

 

About Fast Track designation

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

About Duchenne muscular dystrophy

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

About Pamrevlumab

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

About FibroGen

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

Solid Biosciences reports efficacy and safety data

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

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

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

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

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

 

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

 

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

 

IGNITE DMD Data

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

Functional Data

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

Biomarker Data

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

Patient Reported Outcome Measures (PROMs) Data

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

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

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

 

About SGT-001

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

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

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

 

About Solid Biosciences

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

 

About DMD

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

Article about DMD in Nature.com

Recent studies on Duchenne muscular dystrophy (DMD) have greatly deepened our understanding of the primary and secondary pathogenetic mechanisms. Guidelines for the multidisciplinary care for DMD that address obtaining a genetic diagnosis and managing the various aspects of the disease have been established.

Besides, several therapies that aim to restore the missing dystrophin protein or address secondary pathology have received regulatory approval and many others are in clinical development. This open-access Nature article by Dongsheng Duan, Nathalie Goemans, Shin’ichi Takeda, Eugenio Mercuri and Annemieke Aartsma-Rus discusses all the topics mentioned above.

Read the article in Nature.com. 

Duan, D., Goemans, N., Takeda, S. et al. Duchenne muscular dystrophy. Nat Rev Dis Primers 7, 13 (2021). https://doi.org/10.1038/s41572-021-00248-3

Accepted Published

DOI https://doi.org/10.1038/s41572-021-00248-3