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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.

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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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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.

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News from Vamorolone in Duchenne Muscular Dystrophy

Santhera Announces Completion of First 6-Month Period of Pivotal VISION-DMD Trial with Vamorolone in Duchenne Muscular Dystrophy

Original Press release > Pratteln, Switzerland, March 3, 2021

Santhera Pharmaceuticals announces that the last patient has completed the last visit for the first period of the placebo-controlled pivotal VISION-DMD study with vamorolone in patients with Duchenne muscular dystrophy (DMD), conducted by partner ReveraGen Biopharma Inc. Subject to a positive 6-month topline data readout of this first study phase, this could allow for regulatory submission to the US FDA in Q1-2022 with the potential to offer an alternative to the current standard of care in DMD.

The 48-week Phase 2b VISION-DMD study is designed as a pivotal trial to demonstrate the efficacy and safety of vamorolone administered orally versus prednisone and placebo in ambulant boys aged 4 to <7 years with DMD. Efficacy outcome measures are motor function and strength outcomes with the Time to Stand test (TTSTAND) as the primary study endpoint. Additional analyses compare safety and tolerability between the vamorolone dose groups, placebo and prednisone. In the now completed 24-week, placebo- and active-controlled treatment period, patients were randomized to receive vamorolone 2.0 mg/kg/day, vamorolone 6.0 mg/kg/day, prednisone 0.75 mg/kg/day or matching placebo. For the second treatment period of another 24 weeks of continued study conduct, patients who previously received prednisone or placebo have been randomized and will be switched to one of two doses of vamorolone. This treatment period where all patients receive vamorolone is evaluating the persistence of effect in the longer term. In addition to efficacy, the study aims to confirm the differentiated safety and favourable tolerability profile of vamorolone with the potential to offer an alternative to the current standard of care. Although glucocorticoids are part of DMD’s current care recommendations, their adverse effect profile limits their use as chronic therapy.

 

Eric Hoffman, Ph.D., President and CEO at ReveraGen BioPharma – “We are delighted about having achieved this important milestone and are looking forward to announcing the topline 6-month results of this pivotal study together with Santhera. The use of glucocorticoids, despite having proven benefits in the treatment of DMD, is severely limited due to side effects and poor tolerability. Our expectation is that vamorolone will have the benefits but avoids many of the tolerability issues that limit the use of this standard of care. Our thanks go out to the study participants, their families and healthcare professionals who, in the midst of the COVID-19 pandemic, are enabling us to advance this pivotal study as intended.”

 

Dario Eklund, CEO of Santhera – “Based on previously established data, we believe that vamorolone has the potential to become a foundational therapy in DMD for patients irrespective of the underlying gene mutation and a promising alternative to existing corticosteroids. Our organization is wholeheartedly dedicated to bringing this novel therapy to patients who are hoping for a DMD therapy with fewer treatment-limiting side effects, making it suitable for longer-term administration and also improving quality of life.”

 

 

About Vamorolone – first-in-class dissociative steroid

Vamorolone is a first-in-class drug candidate that binds to the same receptors as corticosteroids but modifies the receptors’ downstream activity. This has the potential to ‘dissociate’ efficacy from typical steroid safety concerns and, therefore, could replace existing corticosteroids, the current standard of care in children and adolescent patients with DMD. There is a significant unmet medical need in this patient group as high-dose corticosteroids have severe systemic side effects that detract from treatment compliance and patient quality of life.

In the pivotal Phase 2b VISION-DMD trial, the last patient has completed the last visit of the 24-week, placebo- and active-controlled treatment period. Topline 6-month data are expected in Q2-2021, paving the way for a US NDA submission in Q1-2022. Vamorolone has been granted Orphan Drug status in the US and Europe and has received Fast Track and Rare Pediatric Disease designations by the US FDA and Promising Innovative Medicine (PIM) status UK MHRA. Vamorolone was discovered by US-based ReveraGen BioPharma Inc. and is being developed in collaboration with Santhera, which owns worldwide rights to the drug candidate in all indications. The vamorolone development program has received funding from several international non-profit foundations and patient organizations, the US National Institutes of Health, the US Department of Defense and the European Commission’s Horizon 2020 program.

Clinical trial in Canada

 

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 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 DuchenneCureDuchenneRyan’s QuestAlex’s WishDuchenneUKPietro’s FightMichael’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).

 

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FDA Approval of AMONDYS 45 (casimersen)

Sarepta Therapeutics announces FDA approval of AMONDYS 45 (casimersen) injection to treat Duchenne muscular dystrophy (DMD) in patients amenable to skipping exon 45.

Feb. 25, 2021, >Original press release<

Sarepta Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) had approved AMONDYS 45 (casimersen). AMONDYS 45 is an antisense oligonucleotide from Sarepta’s phosphorodiamidate morpholino oligomer (PMO) platform, indicated for Duchenne muscular treatment dystrophy (DMD) in patients with a confirmed mutation amenable to exon 45 skipping. This indication is based on a statistically significant increase in dystrophin production in skeletal muscle observed in patients treated with AMONDYS 45, which is reasonably likely to predict clinical benefit for those patients who are exon 45 amenable. Consistent with the accelerated approval pathway, the continued approval of AMONDYS 45 may be contingent on confirmation of a clinical benefit in confirmatory trials.

 

Quickly

  • AMONDYS 45 is Sarepta’s third RNA exon-skipping treatment for DMD approved in the U.S.
  • The commercial distribution of AMONDYS 45 in the U.S. will commence immediately.
  • Information for patients and clinicians is available at www.SareptAssist.com.  

The ESSENCE trial

The ESSENCE trial is a placebo-controlled confirmatory trial to support the AMONDYS 45 approval – it is ongoing and expected to conclude in 2024.

This trial is a double-blind, placebo-controlled, multi-center Phase 3 study evaluating the efficacy and safety of casimersen (SRP-4045 as AMONDYS 45™) 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 undergo a second muscle biopsy either at week 48 or week 96.

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

 

Doug Ingram, president and chief executive officer, Sarepta – “This is an important day for Sarepta and, far more importantly, for the patients that we serve. After years of scientific commitment, investment and development, the approval of AMONDYS 45, Sarepta’s third approved RNA therapy, offers treatment to the 8% of the DMD community who have a confirmed exon 45 amenable mutation. Along with our other approved RNA therapies, we can now offer treatment options for nearly 30% of Duchenne patients in the U.S. And our commitment to bring therapies to the greatest percentage of the DMD community as soon as possible continues.”

 

Marissa Penrod, founder of Team Joseph and parent of an 18-year old with Duchenne – “Decades of research and commitment have fueled and now accelerate our progress towards new treatments for Duchenne. “The extraordinary diligence and persistence of the Duchenne community – patients and families, clinicians and researchers – have led us to today’s approval, where we now have exon-skipping treatments for almost a third of those with Duchenne.”

AMONDYS 45 is priced at parity with Sarepta’s other approved exon-skipping treatments. Patients and physicians can access more information at www.SareptAssist.com or by calling 1-888-727-3782.

About AMONDYS 45

AMONDYS 45 (casimersen) is an antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy in patients who have a confirmed mutation of the DMD gene amenable to exon 45 skipping. AMONDYS 45 uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology 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.

AMONDYS 45 is approved under accelerated review based on an increase in dystrophin production in skeletal muscle of patients amenable to exon 45 skipping. Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials.

AMONDYS 45 has met the full statutory standards for safety and effectiveness and, as such, is not considered investigational or experimental.

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 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.

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 a wheelchair. Cardiac and respiratory muscle problems begin in the teenage years and lead to serious, life-threatening complications. Read more here.

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Italfarmaco provides an update on Givinostat

Italfarmaco provides an update on Givinostat, an ongoing clinical program, in an oral presentation at XVIII International Conference on Duchenne and Becker Muscular Dystrophy.

Feb. 22, 2021, > Original press release on Business Wire <

  • Analyses of long-term study with Givinostat in Duchenne muscular dystrophy boys continue to show delayed disease progression
  • EPYDIS Phase 3 pivotal clinical trial continues as planned, with preliminary results expected in the second quarter of 2022

The Italfarmaco Group announced updates on its clinical development programs with Givinostat, its proprietary histone deacetylase (HDAC) inhibitor, in boys with Duchenne Muscular Dystrophy (DMD), at the virtual XVIII International Conference on Duchenne and Becker Muscular Dystrophy. In the presentation made on February 20, 2021, Paolo Bettica, MD, Ph.D., Chief Medical Officer at the Italfarmaco Group, provided evidence that continues to show a delay in disease progression in DMD boys aged 7-11 years at treatment start, supported by data on the 7-year follow-up period from the long-term study with Givinostat in addition to steroid treatment.

 

Dr. Paolo Bettica – “We are very encouraged to see that the long-term study with Givinostat continues to show a benefit in boys with DMD, which further supports its potential as a treatment. Our Phase 3 pivotal clinical study is on track and continues as planned with 179 boys recruited, and we look forward to announcing the results in the second quarter of next year. We have made significant progress despite the pandemic and instituted procedures to ensure the safety and well-being of all trial participants while being able to continuously provide access to the study drug, as well as to maintain the scientific validity and integrity of the trial. We are grateful to the clinical teams conducting the studies in all of the sites for continuing to work for the benefit of the participants.”

 

The on-going, long-term study (ClinicalTrials.gov: NCT03373968) with Givinostat in boys with DMD is an extension of its Phase 2 trial (ClinicalTrials.gov: NCT01761292). The new follow-up analyses* after more than 7 years of treatment show that the mean age at loss of ambulation in DMD boys treated with Givinostat on top of corticosteroids is 16.0 years contrasted to the one in the Cooperative International Neuromuscular Research Group (CINRG) study, which was 13.4 years (Mc Donald et al., Lancet 2017). Moreover, the yearly rate of change of respiratory parameters such as Forced Vital Capacity % Predicted (FVC%) and Peak Expiratory Flow % predicted (PEF%) is -1.7% and 0% in contrast to the 4 to 6% yearly rate of decline in these parameters as demonstrated in natural history studies of a patient population comparable to the Givinostat cohort (Mayer et al., Paediatr Pulmonol 2015; Henricson et al., Muscle Nerve 2013; Abresch et al., Neuromuscul Disord 2013; Kinane et al., Journal of Neuromuscular Diseases 2018).

 

Prof. Eugenio Mercuri, Professor of Paediatric Neurology at the Catholic University, Rome, Italy, commented on these results, “Overall these results suggest a potential long-term beneficial effect of Givinostat in DMD boys. We look forward to the final results and remain hopeful that these results can support the registration of Givinostat for the treatment of DMD.”

 

In October 2020, the U.S. Food and Drug Administration (FDA) granted a Rare Pediatric Disease designation to Givinostat to treat DMD, which allows an expedited review process for new treatment modalities. The company also received an Orphan Drug designation and Fast Track designation for Givinostat from the FDA.

About Givinostat

Givinostat is an investigational drug discovered through Italfarmaco’s internal research and development efforts in collaboration with Lorenzo Puri (Santa Lucia Foundation, Rome) and his team and partnerships with Telethon and Parent Project aps. It is being evaluated for safety and efficacy for the treatment of Duchenne – and Becker – Muscular Dystrophy. Givinostat inhibits histone deacetylases (HDACs). HDACs are enzymes that prevent gene translation by changing the three-dimensional folding of DNA in the cell. Studies show that Duchenne patients have higher than normal HDAC levels, which may prevent muscle regeneration and trigger inflammation. In the company’s clinical study in DMD boys aged seven to less than 11 years, Givinostat was observed to slow disease progression, significantly increase muscle mass and reduce the amount of fibrotic tissue. Givinostat treatment also significantly reduced muscle tissue necrosis and fatty replacement, two additional parameters related to disease progression (Bettica et al., Neuromuscular Disorder 2016).

About Italfarmaco Group

Italfarmaco is a specialty pharmaceutical company engaged in discovering, developing, manufacturing, and marketing branded prescription and nonprescription products in more than 60 countries on 5 continents. Italfarmaco’s research and development expertise is best demonstrated through its HDAC inhibitor development programs, addressing new therapeutic treatments of specialty and rare diseases. Italfarmaco is dedicated to serving patients whose needs remain largely unmet through marketed drugs and compounds in development. italfarmaco.com

*The results of these analyses are not published yet.

Canadian study locations

  • Canada, Alberta: Kinsmen Research Centre – Alberta Children’s Hospital – Alberta Health Services
  • Canada, British Columbia: The University of British Columbia, Children’s and Women’s Health Centre of BC Branch
  • Canada, Ontario: Holland Bloorview Kids Rehabilitation Hospital
  • Read more on ClinicalTrials.gov

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff.

About Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a disease that almost exclusively affects boys and whose incidence is 1 in 3,500. Duchenne muscular dystrophy (DMD) will rarely 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. Read more here.

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Sarepta announces top-line results for its investigational gene therapy

Sarepta Therapeutics announces top-line results for part 1 of study 102 evaluating SRP-9001, its investigational gene therapy for the treatment of Duchenne muscular dystrophy (DMD)

 

Jan. 7, 2021, >Original press release<

Sarepta Therapeutics, Inc. announced top-line results from Part 1 of Study SRP-9001 (Study 102), an ongoing, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety, efficacy and tolerability of a single dose of SRP-9001 (rAAVrh74.MHCK7.micro-dystrophin) in 41 patients with 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.

Quickly

  • The study met the primary biological endpoint of micro-dystrophin protein expression at 12 weeks post-treatment, measured by western blot, in SRP-9001-treated participants versus placebo.
  • SRP-9001-treated participants showed an increase in NSAA total score compared to placebo at 48 weeks; however, the study did not achieve statistical significance on the primary functional endpoint of improvement in NSAA total score compared to placebo at 48 weeks post-treatment  
  • In the pre-specified analysis by age-group, by which the randomization was stratified, participants aged 4-5 years at the time of treatment with SRP-9001 demonstrated a statistically significant improvement in NSAA total score age-matched placebo cohort, achieving a 4.3-point improvement on NSAA at 48 weeks post-treatment from baseline.
  • No new safety signals were identified for SRP-9001, reinforcing the favourable safety profile observed to date.

Study 102 is ongoing and remains blinded to participants, investigators, site staff and sponsor staff with direct site interaction. All 41 participants have completed their Part 1, 48-week assessment and have entered the Part 2 crossover phase. Participants continue to be monitored for safety and will undergo another biopsy at week 12 in Part 2 to assess the expression and biological markers, in addition to longer-term assessments of functional outcomes.

 

Doug Ingram, president and chief executive officer, Sarepta – “Study 102 reinforces our confidence in the potentially transformative benefits of SRP-9001, including among other things, the fact that in the Study’s pre-specified analysis, the participants in the 4-5 age group robustly achieved a statistically significant and clinically meaningful improvement in NSAA over placebo, as predicted by our prior Study 101. For the entire population, while we saw separation at every time point between the active and placebo cohorts, Study 102 did not achieve statistical significance on the primary functional endpoint. In this regard, we are very disappointed that the randomization process resulted in a significant imbalance in baseline NSAA scores between the active and placebo cohorts of the participants ages 6-7, making the 6-7 age groups non-comparable and likely substantially contributing to the inability to achieve statistical significance. Study 102 remains blinded and we will analyze the functional results for all patients, including cross-over participants, once they have achieved the 48-week timepoint in Part 2. We have already enrolled and dosed 11 participants in Study 103, using our commercial process material, and we will have biomarker and safety results from that cohort in the second quarter. And very importantly, Study 102 has provided us with a wealth of information and insight which we will use to refine and complete the protocol for our upcoming trial using commercial process material. We intend to continue to move forward with diligence and urgency to generate the evidence necessary to bring SRP-9001 to waiting Duchenne patients around the world.”

 

*The NSAA is a 17-item rating scale used to measure functional motor abilities in ambulant children with Duchenne. It is used to monitor the disease’s progression and treatment effects, which makes it suitable as an endpoint in clinical trials for Duchenne.

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 daily living activities such as using the restroom, bathing and feeding. Eventually, increasing breathing difficulty 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 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, 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 Sarepta

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

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Pfizer doses the first participant with Its gene therapy

Pfizer doses the first participant in phase 3 study for Duchenne muscular dystrophy (DMD) investigational gene therapy.

Pfizer Inc. announced that the first participant has been dosed in the Phase 3 CIFFREO study, which will evaluate the efficacy and safety of investigational gene therapy candidate PF-06939926 in boys with Duchenne muscular dystrophy (DMD). The CIFFREO trial is expected to enroll 99 ambulatory male patients, ages 4 through 7, across 55 clinical trial sites in 15 countries. The first patient was dosed at a site in Barcelona, Spain, on December 29, 2020.

CIFFREO is a Phase 3 global, multicenter, randomized, double-blind, placebo-controlled study. The study’s primary endpoint is the change from baseline in the North Star Ambulatory Assessment (NSAA) at one year. The NSAA is a 17-item test that measures gross motor function in boys with DMD. Regardless of the cohort, eligible participants are scheduled to receive the investigational gene therapy, either at the start of the study or after one year following treatment with placebo. Participants will be followed in the CIFFREO study for five years after treatment with the investigational gene therapy. Trial participants will receive commercially representative drug products manufactured at Pfizer’s state-of-the-art gene therapy manufacturing facility in Sanford, North Carolina.

 

Brenda Cooperstone, MD, Chief Development Officer, Rare Disease, Pfizer Global Product Development  – “The initiation of our pivotal trial, which is the first Phase 3 DMD gene therapy program to begin enrolling eligible participants, is an important milestone for the community because there are currently no approved disease-modifying treatment options available for all genetic forms of DMD. We believe our gene therapy candidate, if successful in Phase 3 and approved, has the potential to significantly improve the trajectory of DMD disease progression, and we are working with worldwide regulatory authorities to initiate this program as quickly as possible in other countries.”

 

PF-06939926 received Fast Track designation from the U.S. Food and Drug Administration in October 2020 (read article), as well as Orphan Drug and Rare Pediatric Disease designations in the United States in May 2017.

 

Silvia Avila, President, Duchenne Parent Project Spain  – “DMD is a progressive disorder, and patients and parents are waiting desperately for treatment options. The initiation of this study is an important step forward for this community, and it fuels us with hope that one day there may be treatment options for boys impacted with this devastating disease.”

 

DMD is an X-linked disease caused by mutations in the gene encoding dystrophin, which is needed for muscle membrane stability. Due to the lack of dystrophin, boys 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 ~140,000 boys affected by DMD worldwide.

 

About CIFFREO

CIFFREO is a Phase 3 global, multi-center, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of PF-06939926 investigational gene therapy in 99 ambulatory male participants, ages 4 through 7 years, with a genetic diagnosis of DMD who are on a stable daily regimen of glucocorticoids. The participants are negative for neutralizing antibodies against AAV9, as measured by the test done for the study as part of screening.

Eligible participants will be randomized into Cohort 1 or Cohort 2. Treatment will consist of two single intravenous infusions, one of PF-06939926 and one of placebo; approximately two thirds will be in Cohort 1 and receive PF-06939926 gene therapy at the start of the study and placebo after one year, and approximately one third will be in Cohort 2 and receive placebo at the start of the study and receive gene therapy after one year if they remain eligible. All participants will be followed in an open-label extension study for 5 years after treatment with the gene therapy. The study’s primary endpoint is a change from baseline at one year in the North Star Ambulatory Assessment (NSAA) total score. For more information, visit ciffreoduchennetrial.com.

 

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.

 

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 diseases 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.