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Translarna: Update for Non-Ambulatory Patients with DMD

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

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

 

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

 

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

 

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

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

About Translarna (ataluren)

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

 

Ataluren in Canada

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

 

About PTC Therapeutics

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

 

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Sarepta is seeking the approval of casimersen for DMD patients

Sarepta Therapeutics Completes Submission of New Drug Application Seeking Approval of Casimersen (SRP-4045) for Patients with Duchenne Muscular Dystrophy Amenable to Skipping Exon 45

  • Casimersen is designed for the treatment of exon 45 amenable patients, approximately eight percent of patients with Duchenne
  • Casimersen is the third exon-skipping medicine using the Company’s proprietary PMO RNA-based platform. 

 

CAMBRIDGE, Mass., June 26, 2020 (GLOBE NEWSWIRE) >Original press release here

Sarepta Therapeutics, Inc. has completed the submission of a rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for casimersen (SRP-4045). Casimersen, a phosphorodiamidate morpholino oligomer (PMO), is engineered to treat patients with Duchenne muscular dystrophy (DMD) who have genetic mutations that are amenable to skipping exon 45 of the Duchenne gene.

The completion of the rolling submission includes data from the casimersen arm of the ESSENCE study (also known as study 4045-301), a global, randomized, double-blind, placebo-controlled Phase 3 study evaluating efficacy and safety in patients amenable to skipping exons 45 and 53. An interim analysis from ESSENCE demonstrated a statistically significant increase in dystrophin production as measured by western blot* in patients who received casimersen compared to baseline and placebo. The study is ongoing and remains blinded to collect additional efficacy and safety data. If the casimersen NDA is accepted and granted accelerated approval, the completed ESSENCE study will serve as a post-marketing confirmatory study.

 

Doug Ingram, president and chief executive officer, Sarepta Therapeutics. – “The completion of our casimersen submission is an important milestone in our journey to advance treatments for the greatest possible number of people living with Duchenne muscular dystrophy. If approved, casimersen will be our third approved therapy for sub-populations of Duchenne. Together with our other approved therapies, we have the potential to treat nearly 30% of Duchenne patients in the United States. Our proprietary PMO platform is an important focus of our pipeline, and we owe our clinical progress to the patients and families participating in our studies.”

 

About Casimersen

Casimersen uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 45 of the DMD gene. Casimersen is designed to bind to exon 45 of dystrophin pre-mRNA, resulting in exclusion, or “skipping,” of this exon during mRNA* processing in patients with genetic mutations that are amenable to exon 45 skipping. Exon skipping is intended to allow the production of an internally truncated dystrophin protein.

What about Canada?

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

For a better understanding

  • * The western blot is a widely used analytical technique in molecular biology, immunogenetics and other molecular biology disciplines to detect specific proteins in a sample of tissue homogenate or extract.
  • * Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and DNA are nucleic acids and, along with lipids, proteins and carbohydrates, constitute the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA, it is more often found in nature as a single-strand folded onto itself, rather than a paired double-strand.
  • Read more here
  • Grounded in the DMD community

About DMD

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

About Sarepta Therapeutics

The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Company’s programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visit www.sarepta.com or follow them on TwitterLinkedInInstagram and Facebook.

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Positive Safety and Efficacy Data from Micro-Dystrophin Gene Therapy

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

 

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

Sarepta Therapeutics, Inc. announced safety and tolerability data at one year from four Duchenne muscular dystrophy (DMD) clinical trial participants who received SRP-9001 micro-dystrophin (AAVrh74.MHCK7.micro-dystrophin) have been published in JAMA Neurology. SRP-9001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of micro-dystrophin protein.

 

Louise Rodino-Klapac, Ph.D., senior vice president of gene therapy, Sarepta Therapeutics –  “We are encouraged by the successful and safe systemic delivery of our micro-dystrophin transgene from our AAVrh74 viral capsid and targeted muscle expression results, demonstrating the safety and efficacy of SRP-9001 gene transfer maintained over one year in this cohort of participants living with Duchenne muscular dystrophy. Following the 9-month update we shared last year, the peer-reviewed publication of these results in JAMA Neurology further supports the potential for SRP-9001 to provide clinically meaningful functional improvements in terms of speed and magnitude of improvement for patients with DMD.  Study 102, our randomized, double-blind, placebo-controlled study of SRP-9001, is ongoing and we look forward to sharing the results in early 2021 as we work toward our ultimate goal of profoundly improving the lives of as many patients living with DMD as possible.”

 

In the open-label trial, known as Study 101, four ambulatory participants between the ages of 4 and 7 were treated with an infusion of SRP-9001 at a dose of 2×1014 VG/kg. The therapy was safe and tolerable in all participants over the one-year time period. All adverse events were considered mild or moderate, and there were no serious adverse events or evidence of complement activation.  At 12 weeks, muscle dystrophin levels demonstrated a mean of 81.2% muscle fibers expressing micro-dystrophin with a mean intensity at the sarcolemma by immunohistochemistry of 96% compared to normal biopsies. Adjusted for fat and fibrotic tissue, western blot showed a mean expression of 95.8%. All participants had confirmed vector transduction and showed functional improvement on the North Star Ambulatory Assessment scale (NSAA) and reduced creatine kinase (CK) levels that were maintained through one year.

 

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

 

 

About SRP-9001

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

 

About DMD

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

 

About Sarepta Therapeutics

The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Company’s programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visit www.sarepta.com or follow them on TwitterLinkedInInstagram and Facebook.

More links

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Press release from Pfizer about gene therapy

Pfizer’s new phase 1b results of gene therapy in ambulatory boys with Duchenne muscular dystrophy (DMD) support advancement into pivotal phase 3 study

Read the press release here.

Friday, May 15, 2020
Pfizer Inc. announced updated Phase 1b clinical data on PF-06939926, an investigational gene therapy being developed to treat Duchenne muscular dystrophy (DMD). The preliminary data from 9 ambulatory boys with DMD, aged 6 to 12 indicate that the intravenous administration of PF-06939926 was well-tolerated during the infusion period, with encouraging efficacy and manageable safety events, even when considering those adverse events that were more severe in nature. The treatment provided durable and statistically significant improvements across multiple efficacy-related endpoints measured at 12 months post-infusion, including sustained levels of mini-dystrophin expression and improvements on the North Star Ambulatory Assessment (NSAA) rating scale, which is a validated measure of muscle function. Three serious adverse events (SAEs) were recorded, two of which reflected likely complement activation. While these two SAEs were severe in nature, all three events fully resolved within 2 weeks, providing encouragement that close monitoring and early intervention can help mitigate the effects of complement activation. This new dataset, which includes updated 12-month results on safety, dystrophin expression, and exploratory functional endpoints for 3 additional boys, was presented for the first time during a virtual oral session at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting.

 

Seng Cheng, Ph.D., Chief Scientific Officer, Pfizer Rare Disease Research Unit – “Based on the encouraging preliminary efficacy data and manageable safety events from our Phase 1b study, we believe we may have a potential breakthrough therapy for boys with Duchenne muscular dystrophy, a devastating disease for which there remains a significant medical need. We are advancing our Phase 3 program as quickly as possible and plan to begin dosing patients in the second half of 2020 pending regulatory approval. Our program has the potential to be the first DMD gene therapy Phase 3 trial start using a commercial-scale manufacturing process. If the program is successful, this manufacturing capability is expected to help position us to deliver this medicine to patients quickly following regulatory approval.”

 

Preliminary Safety Results

The primary endpoint of the Phase 1b study is to assess the safety and tolerability of this investigational gene therapy in ambulatory boys with Duchenne muscular dystrophy through 12 months following treatment. Based on the data to date, the most common adverse events (AEs) suspected to be related to PF-06939926 (occurring in >40% of patients) were vomiting, nausea, decreased appetite, and pyrexia (fever). There was no evidence of clinically relevant anti-dystrophin responses or hepatic dysfunction with the protocol-defined daily glucocorticoid regimen. Continue reading here.

Results from Secondary and Exploratory Endpoints

Secondary endpoints of the clinical study included measurement of mini-dystrophin concentration by liquid chromatography-mass spectrometry (LCMS) and distribution within muscle fibers by immunofluorescence.

Read more about: dystrophin concentration, dystrophin distribution and the functional assessment here.

 

Seng Cheng, Ph.D., Chief Scientific Officer, Pfizer Rare Disease Research Unit – “Taken together, we believe these data support the view that administration of PF-06939926 at a dose of 3E14 VG/kg can lead to the expression of potentially therapeutic levels of mini-dystrophin that may translate to a measurable improvement in muscle function and health in DMD patients. We also want to give our heartfelt thanks to all the patients, their families, the researchers, investigators, other clinicians and advocacy organizations for their passion, expertise and engagement in helping to advance clinical research and care for the Duchenne muscular dystrophy community.”

 

About PF-06939926

PF-06939926 is an investigational, recombinant adeno-associated virus serotype 9 (AAV9) capsid carrying a shortened version of the human dystrophin gene (mini-dystrophin) under the control of a human muscle specific promotor. The AAV9 capsid was chosen as the delivery vector because of its potential to target muscle tissue. Pfizer initiated the Phase 1b multi-center, open-label, non-randomized, ascending dose study of a single intravenous infusion of PF-06939926 in 2018. The goal of the study is to assess the safety and tolerability of this investigational gene therapy. Other objectives of the clinical study include measurement of dystrophin expression and distribution, as well as assessments of muscle strength, quality and function.

 

About Pfizer

Pfizer’s innovative portfolio focuses on the discovery and development of new medicines and vaccines. By focusing on the best science and patient experience, Pfizer’s leadership and significant investments support faster delivery of breakthrough medicines that can fulfill unmet needs.

Interesting link

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

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Latest edition of the Catabasis Connection newsletter

La Force is happy to share the latest edition of the Catabasis Connection newsletter with updates on edasalonexent and information that Catabasis shared at the MDA Virtual Poster Session.

Earlier this month, Catabasis shared data from three scientific posters during the Muscular Dystrophy Association (MDA) Virtual Poster Session. Learn more about edasalonexent and its potential to provide positive effects in Duchenne here.

In this newsletter you can read:

  • Boys with Duchenne demonstrate capsule swallowing abilities
  • Phase 3 PolarisDMD trial enrolled expected patient population
  • Age-normative growth and normal adrenal function observed with edasalonexent

About Edasalonexent (CAT-1004)

Edasalonexent (CAT-1004) is an investigational oral small molecule designed to inhibit NF-kB that is being developed as a potential foundational therapy for all patients affected by DMD, regardless of their underlying mutation. In DMD the loss of dystrophin leads to chronic activation of NF-kB, which is a key driver of skeletal and cardiac muscle disease progression. Our ongoing global Phase 3 PolarisDMD trial is evaluating the efficacy and safety of edasalonexent for registration purposes. Edasalonexent is also being dosed in the open-label extension trial GalaxyDMD. In our MoveDMD Phase 2 trial and open-label extension, we observed that edasalonexent preserved muscle function and substantially slowed disease progression compared to rates of change in a control period, and significantly improved biomarkers of muscle health and inflammation. The FDA has granted orphan drug, fast track, and rare pediatric disease designations and the European Commission has granted orphan medicinal product designation to edasalonexent for the treatment of DMD. For a summary of clinical results, please visit www.catabasis.com.

About Catabasis

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

About La Force DMD

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

 

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

COVID-19 for people affected by Duchenne or Becker #3

What we know about COVID-19 part 3

What do we know about COVID-19 for people affected by Duchenne or Becker? Due to the increasing concerns regarding the COVID-19 virus for people with Duchenne and Becker muscular dystrophy, the World Duchenne Organization had hosted their third webinar last Saturday for its members.  Information is provided by World Duchenne Organization.

In the third WDO Webinar, Prof. Dr. Jan Verschuuren, head of the neurology department at the LUMC in the Netherlands, shares how they have prepared their hospital for potential DMD/BMD patients with COVID-19.

Preventive Measures

Since there is no vaccine against the virus or cure against the disease, and most medicines are used to model the course of the disease, prevention is really key. Luckily, people with Duchenne are very aware when it comes to infection during this time of the year. Most families are already isolating at home and make sure they have a small group of people around them. You cannot be isolated completely due to the care you need. However, these team members need to respect social distancing and hygiene rules strictly.

In case you need to go to the hospital, you need to make sure you have clear information with you about the diagnosis, the medication you are taking and your ventilatory devices. Bring your ventilatory devices with you. You need to have the names and contacts of doctors in the field of Duchenne because if you are admitted to the hospital you may be seen by another doctor and there will be a lot of stress.

Read more >

Create Awareness In Hospitals On Potential COVID-19 Duchenne Patients

World Duchenne Organization also wrote a letter to occupational physicians. They made the statement that if you’re working in healthcare and have a boy with Duchenne, you should be allowed to stay at home and care for the boy to minimize the risk of infecting your own child. This also applies to carers that do not work in a healthcare facility, although the chance of being infected is probably lower than for those that work in a hospital and come in direct contact with patients. [ Read more here. ]

To-Do’s

  • Maximize your efforts to try and prevent infection
  • Get your clinician’s information so you can contact them in case of an emergency
  • When admitted to the hospital, immediately state your diagnosis and that you need special attention
  • Make sure you have protective gear such as masks for your carers
  • Contact your hospital and ask if they are prepared for a possible COVID-19 DMD case

 

This is the report of one webinar from the webinar series the World Duchenne Organization is hosting regarding the current COVID-19 pandemic. Please consult your clinician if you have specific questions on the medicines regimen. This information meant as general recommendations and does not replace personal medical advice.

More links

All questions and answer here: www.worldduchenne.org

COVID-19 for people affected by Duchenne or Becker #2

What we know about COVID-19 part 2

What do we know about COVID-19 for people affected by Duchenne or Becker? Due to the increasing concerns regarding the COVID-19 virus for people with Duchenne and Becker muscular dystrophy, the World Duchenne Organization had hosted a second webinar last Saturday for its members.  Information is provided by World Duchenne Organization.

What is the effect of steroids on the immune system?

Dr. Jarod Wong, an endocrinologist at Glasgow University – “Steroids prescribed for DMD may have some impact on lowering the immune system. Hence, routine flu vaccination is recommended. People taking steroids have been identified as an at-risk group in the current climate by some governments. However, we do not commonly see severe, unusual and serious infections in people with DMD on steroids.”

What is the effect of steroids and COVID-19 infection in DMD?

Dr. Jarod Wong, an endocrinologist at Glasgow University – “At the moment, we are not aware of any cases of people with DMD and COVID19 infection. It is theoretically possible that if infected, the infection may be more severe. However, we simply do not know. In some countries, any person on long term steroids has been classified as at-risk and recommended to isolate for a longer period of time, for instance, 12 weeks.”

Should I stop steroids in this instance then?

Dr. Jarod Wong, an endocrinologist at Glasgow University – “No, this should not happen and is not possible. One issue with anyone taking steroids for a prolonged period i.e. longer than a few months is that the adrenal glands, which make steroids naturally, are suppressed (ADRENAL SUPPRESSION LEADING TO ADRENAL INSUFFICIENCY). Even if we do want to stop steroids, a slow plan of gradual reduction over several months is essential. To cope with severe infection, extra steroids are needed – stress dosing. Otherwise, the person could become very ill and be in an adrenal crisis. One possibility of more severe infection (of all kinds) in people with adrenal suppression from taking steroids may be that steroid management during the illness is not adequate.”

Is there anything extra you need to do if on steroids during (COVID) illness?

Dr. Jarod Wong, an endocrinologist at Glasgow University – “Regardless of the type of infection in a person with DMD taking steroids, if the person has vomiting and/or diarrhea, steroids should be given in another form. If there is access to steroids in the form of hydrocortisone injection at home, this needs to be given and then presented to the hospital. In some people with DMD on steroids (especially older boys or men on lower doses of steroids), there may be a need to increase the dose of oral steroids during mild to moderate illness, which includes fever. It would be worth checking with your neuromuscular team if this is needed. In the majority of cases, this may not be necessary. Some teams have been advising all their patients to do so to be on the safe side. Generally, this should be for a period of 48 hours but maybe longer if the person is sick. Currently, if the symptoms might be COVID related and do not resolve within 48 hours, generally the advice is to contact the relevant places for COVID advice, for instance, the national hotline. For those on intermittent steroids, a steroid plan should be in place with information on what to do if the person with DMD is unwell during the days off steroids.”

Is it true steroids might have a positive effect on COVID-19?

Prof Dr. Annamaria De Luca, pharmacologist in Italy – “It has been proposed that low dosage of steroids can be useful in a so-called cytokine storm. This is a severe phenomenon that might occur in COVID-19 patients in an advanced stage of pneumonia. Normally, our immune system can combat the infection, however, at a certain stage, there could be an excessive discharge of the virus from the infected cells, leading to massive production of cytokines. China proposed that low doses of glucocorticoids such as alpha methyl prednisolone can help reduce the storm without causing immunosuppression. There are clinical trials ongoing in COVID-19 patients, but there is some debate about the real usefulness of steroids in this condition, especially in patients already on steroids. With the information and data we have, it’s important not to stop steroids unless specifically indicated. This is also valid for other Standards of Care in patients, i.e. those receiving treatment with ACE inhibitors. It’s best to maintain drugs that are effective in controlling cardiovascular function, as evidence of the potential risk of ACE inhibitors are few and controversial.”

More links

All questions and answer here: www.worldduchenne.org

Webinar #1

Webinar #2

15 THINGS WE KNOW SO FAR

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Edasalonexent and COVID-19

La Force is happy to share the latest edition of the Catabasis Connection newsletter. As we are all faced with an unimaginable situation, Catabasis wanted to reach out and share information in response to questions they have been receiving about edasalonexent and COVID-19.

Catabasis is monitoring the trial for the safety of participating boys. To date, they did not identify any safety concerns related to COVID-19. We encourage reviewing your local recommendations to reduce the risk for boys and their families, and please consult your physician regarding specific medical advice. > Catabasis Connection <

Does edasalonexent affect the immune system?

Long-term toxicology studies with edasalonexent using higher doses than those in their clinical trials have found no evidence for immunosuppression using standard clinical and anatomic physiology methods. In clinical studies, now with over 100 patient-years of exposure to edasalonexent, Catabasis has found no evidence of immunosuppression or increased infections. In the Phase 3 PolarisDMD trial of edasalonexent, as well as the GalaxyDMD open-label trial, boys are not on steroids.

Should trial participants still go to the hospital for their assessments?

They are fortunate that site visits are relatively infrequent during the Phase 3 PolarisDMD trial with assessments every 3 months. Currently, they are focused on ensuring that patients have uninterrupted drug supply as well as safety monitoring. Catabasis is working closely with its clinical trial sites with frequent communication.

Will the outcome of ongoing trials be endangered by not being able to carry them out as per protocol?

Catabasis is actively monitoring the situation and has plans in place to address potential disruptions. Fortunately, they designed their clinical trial so that visits are relatively infrequent. Catabasis is working with sites to support drug supply, as well as safety and efficacy assessments.

About Catabasis

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

About La Force DMD

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

 

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

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COVID-19 for people affected by Duchenne or Becker

WHAT WE KNOW ABOUT COVID-19

What do we know about COVID-19 for people affected by Duchenne or Becker? Due to the increasing concerns regarding the COVID-19 virus for people with Duchenne and Becker muscular dystrophy, the World Duchenne Organization had hosted a webinar last Saturday for its members.  All these information are provided by World Duchenne Organization

General information

  • It’s a respiratory virus that can be spread by aerosols: little droplets when you cough or sneeze.
  • Symptoms are coughing, having fever, shortness of breath and difficulty breathing.
  • The virus can survive for hours on hard surfaces, so you don’t have to see the person who is symptomatic and spreading.
  • The highest risks are the older population above 60 and vulnerable people.
  • This Wednesday, the WHO officially declared COVID-19 a pandemic.

Stanford University School of Medicine Webinar ‘Coronavirus for non-virologists

And DMD/BMD

  • There is no expertise about Duchenne / Becker muscular dystrophy and the coronavirus as we don’t know any DMD/BMD patient affected by it
  • We have asked DMD experts to give a reaction to the questions of our families
  • Situation and national rules will be different in all countries

 

How to follow instructions if resources are scarce?

Prof. Dr. Jonathan Finder –“The best way to protect your sons is the avoidance of crowds and careful handwashing with soap and water.”

Prof. Dr. Nathalie Goemans –“We cannot stress enough the rules of common sense and hygiene, applicable to the general population and even more important for the helpers and caregivers.”

Elizabeth Vroom –“Next to washing your hands often, it’s necessary to clean surfaces, door handles and touch screens regularly.”

 

What impacts do steroids have on the immune system?

Prof. Dr. Jonathan Finder –“Steroids are a mild immunosuppressant and reduce the activity of lymphocytes, and these are the cells that help fight off viruses.”

 

Do people DMD/BMD patients have a higher chance of catching the virus?

Prof. Dr. Jonathan Finder – “No, and possibly they have a lower risk given that they are less likely to be touching doorknobs and handles and shake hands and the like. Those in schools or just out and about have the same risk from respiratory droplets.”

Prof. Dr. Nathalie Goemans – “We cannot stress enough that containing this epidemic is everyone’s responsibility, we should all temporarily restrict our contacts and stay as much as possible at home, respecting strict measures of hygiene.”

 

When infected, will it take them longer to fight it off?

Prof. Dr. Jonathan Finder –“We have no information about this. Presuming that steroids are being used, it is likely that the illness will be a bit harder to fight since steroids are mildly immunosuppressant. This is NOT to say that one should stop steroids: DO NOT STOP STEROIDS, as this is dangerous and riskier than the possible risks of COVID-19.”

Prof. Dr. Nathalie Goemans –“Yes, it is known that a severe course of COVID-19 can cause permanent damage to the lungs. On a positive note: although steroids are known to reduce immunity, it might well be that steroids could have a protective role in the pathophysiology (cytokine-storm) of severe ARDS in COVID-19 but we don’t know yet.”

 

Are they at higher-risk or ‘vulnerable people’ most likely to die?

Prof. Dr. Jonathan Finder – “They are at higher risk to be sure as the illness is a viral pneumonia, and having pneumonia is a risk for respiratory failure in this population. But as for “more likely to die” I would say NO as these patients are younger and for the most part do not have underlying lung disease. Those with chronic lung disease are the highest risk group, along with the elderly.

On the other hand, cardiac disease is a risk factor, and there is a great deal of cardiac disease in the DMD population. Thus I do have concerns about the risk of COVID-19 infection for those patients with heart failure.”

 

More answer here < WDO Webinar: COVID 19 and Duchenne & Becker muscular dystrophy >

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Viltolarsen under priority review by the FDA

The U.S. Food & Drug Administration (FDA) had accepted the filing of a New Drug Application (NDA) under the priority review for viltolarsen in patients with Duchenne Muscular Dystrophy (DMD) who are amenable to exon 53 skipping therapy.

Read the full News Release

KYOTO, Japan and PARAMUS, NJ: February 7, 2020 –

Nippon Shinyaku Co., Ltd. and NS Pharma, Inc. announced that the U.S. Food & Drug Administration (FDA) had accepted the filing of a New Drug Application (NDA) under the priority review for viltolarsen in patients with Duchenne Muscular Dystrophy (DMD) who are amenable to exon 53 skipping therapy. In addition to priority review, the FDA previously granted viltolarsen with Fast Track, Orphan Drug and Rare Disease designations. The viltolarsen NDA includes results from a Phase 2 study and its long-term extension study in North America — as well as a Phase 1 and a Phase 1/2 study in Japan. Both the Phase 1/2 and Phase 2 studies evaluated changes in dystrophin levels and motor function across two doses. The PDUFA (Prescription Drug User Fee Amendments) date for viltolarsen is within the 3 rd quarter (July-September) of 2020. The PDUFA date is the target date the FDA provides a decision on the approval of a new drug. Viltolarsen represents one of the most extensively studied antisense therapies in DMD. Viltolarsen, if approved by the FDA, would represent a new treatment option for DMD patients amenable to exon 53 skipping in the United States.

About Viltolarsen

Viltolarsen has been granted a Rare Pediatric Disease Designation, Orphan Drug Designation, and a Fast Track Designation in the U.S., and “SAKIGAKE designation,” “Orphan drug designation,” and designation of Conditional Early Approval System in Japan. Viltolarsen is not approved by any regulatory authority and its safety and effectiveness have not been established.

Mechanism of Action

Exon skipping is a potential therapy that is being developed for patients with DMD. Specialized molecules are created to skip over the non-working part of the dystrophin gene and allow pieces of the puzzle to attach. It creates a smaller puzzle, but a puzzle that may produce some of the protein that muscles need to work correctly. NS-065/NCNP-01-201 Phase II dose-finding study is evaluating the safety and dosing of an investigational medication called NS-065/NCNP-01 (Viltolarsen), in the treatment of boys with DMD who have specific changes in the dystrophin gene that may be helped with the skipping of exon 53.

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