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.



  • 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.


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.

Rare disease day 2021 – La Force DMD

We wish to emphasize that the information contained in this article comes mainly from the RQMO website, the CORD website and the Rare Disease Day website. We thank them.

February 28th is Rare disease day 2021. Because it manifests itself only rarely, Duchenne muscular dystrophy (DMD) falls within the rare diseases category. Since this is February, it is pertinent for us to tell you about it.  Learn about our history here. Over 6,000 rare diseases are characterized by a broad diversity of disorders and symptoms that vary from disease to disease and from patient to patient suffering from the same disease. Relatively common symptoms can hide underlying rare diseases leading to misdiagnosis and delaying treatment. Quintessentially disabling, the patient’s quality of life is affected by the lack or loss of autonomy due to the chronic, progressive, degenerative, and frequently life-threatening aspects of the disease. There are often no existing effective cures that add to patients and their families’ high level of pain and suffering. Read more here


About Rare Diseases

  • Over 300 million people live with one or more of over 6,000 identified rare diseases around the world.
  • Each rare disease may only affect a handful of people scattered around the world, but taken together, the number of people directly affected is equivalent to the population of the world’s third-largest country.
  • Rare diseases currently affect 3.5% – 5.9% of the worldwide population.
  • 72% of rare diseases are genetic, while others result from infections (bacterial or viral), allergies and environmental causes, or degenerative and proliferative diseases.
  • 70% of those genetic rare diseases start in childhood.
  • A disease is defined as rare in Europe and Canada when it affects fewer than 1 in 2,000 people.


Canada and rare diseases

About 1 in 12 Canadians, two-thirds of them children, are affected by a rare disorder. But because each disease affects only a small number of individuals, understanding and expertise may be limited and fragmented across the country.

Only 60% of treatments for rare disorders make it into Canada, and most get approved up to six years later than in the USA and Europe. People with rare disorders in Canada miss out on treatments that could save or significantly improve their lives.  This needs to change.

Genetic changes cause about 80% of rare diseases. 25% of children with a rare disease will not live to see their 10th birthday.

A rare disease is a condition affecting fewer than 1 person in 2,000 in their lifetime. There are over 6,000 known rare diseases and dozens more being discovered each year, so in total, 1 in 12 Canadians will be affected by a rare disease.


Who is CORD?

CORD is Canada’s national network for organizations representing all those with rare disorders. CORD provides a strong common voice to advocate for health policy and a healthcare system that works for those with rare disorders. CORD works with governments, researchers, clinicians and industry to promote research, diagnosis, treatment and services for all rare disorders in Canada.

How does CORD serve Canadians with Rare Disorders?

1 in 12 Canadians has a rare disorder. Many others are affected or at risk but remain undiagnosed and unaware. CORD provides information to individuals and links to other rare disorder support groups and organizations from Prince Rupert, British Columbia, to St. John’s, Newfoundland.

What are CORD’s Key Challenges?

CORD represents the orphan disorders community in the development of the Canadian Orphan Drug Policy, including the proposed Expensive Drugs for Rare Disorders program within the National Pharmaceutical Strategy CORD is working to promote state-of-the-art Newborn Screening in all provinces and territories. CORD is working to ensure Canada’s Clinical Trials Registry works effectively for those with rare disorders. CORD is committed to increasing access to genetic screening and genetic counselling for all rare disorders.

CORD Strategy

The Canadian Organization for Rare Disorders (CORD) has released Canada’s Rare Disease Strategy, developed with experts from every sector.  The Strategy details the extraordinary burden faced by Canadian families with rare illnesses. Challenges include misdiagnosis, unnecessary surgeries, social isolation, financial hardship, lack of treatment options and early death. These are the same challenges faced by Canadians with “non-rare” conditions, but the impact is often much more severe. The Strategy proposed a five-point action plan that will address unnecessary testing delays, wrong diagnoses and missed opportunities to treat.


About Rare Disease Day

Rare Disease Day takes place on the last day of February each year. Rare Disease Day’s main objective is to raise awareness amongst the general public and decision-makers about rare diseases and their impact on patients’ lives.

The campaign primarily targets the general public and seeks to raise awareness amongst policymakers, public authorities, industry representatives, researchers, health professionals and anyone who has a genuine interest in rare diseases.

Building awareness of rare diseases is important because 1 in 20 people will live with a rare disease at some point in their lives. Despite this, there is no cure for the majority of rare diseases, and many go undiagnosed. Rare Disease Day improves knowledge amongst the general public of rare diseases while encouraging researchers and decision-makers to address the needs of those living with rare diseases.

Equity for people living with a rare disease

What equity means for people living with a rare disease? Equity in practice means meeting people’s specific needs and eliminating barriers preventing their full participation in society. For people living with a rare disease, equity means social opportunity, equitable access to health and social care, diagnosis and treatment. On Rare Disease Day, we call for action for people living with a rare disease to have equal opportunities to realize their potential for participation in family, work and social life. Rare Disease Day’s long-term goal over the next decade is increased equity for people living with a rare disease and their families.

The challenge

The 300 million people living with a rare disease worldwide and their families face common challenges in their daily lives. As a vulnerable and neglected population, they face social isolation. There are over 6,000 rare diseases that are chronic, progressive, degenerative, disabling and frequently life-threatening. Due to the rarity of each disease and scattered populations, expertise and information are scarce. In health systems designed for common diseases, patients face inequities in accessing diagnosis, care and treatments.


How can we achieve equity for people living with a rare disease?

Advocating for the social inclusion of people living with a rare disease

To achieve equitable social inclusion for people living with a rare disease, they must first have access to holistic care covering the 360° spectrum of health, social and everyday needs.

The United Nations 2030 Agenda and its Sustainable Development Goals provide an important framework for addressing the full spectrum needs of people living with a rare disease. The Goals target issues beyond health, including education, gender, work and inequality.

Global institutions protecting human rights seek to address the health care challenges of people living with a rare disease. The Human Rights Council Resolution on access to medicines and vaccines recognizes the importance of development, access and affordability of rare disease treatments.

The following legislation promotes social inclusion for people with a disability, including those whose disability is a result of living with a rare disease: The UN Convention on the Rights of People with Disabilities (CRPD) and the report of the Special Rapporteur on the rights of persons with disabilities to 73rd Session of the UNGA.

Including rare diseases in universal health coverage to leave no one behind

Addressing the needs of people living with a rare disease is central to achieving the UN 2030 Agenda and its Sustainable Development Goals and its pledge to leave no one behind.

To achieve this, we should move towards a strategy for universal health coverage (UHC) that addresses the needs of those living with a rare disease.

The United Nations Office of the High Commissioner for Human Rights (OHCHR) stressed the need to address rare diseases within UHC in the annual report to the UN Economic and Social Council (ECOSOC).

A hugely significant milestone has been reached with the inclusion of rare diseases in the political declaration on UHC adopted by all UN Member States, thanks to the rare disease community’s advocacy efforts, led by EURORDIS, Rare Diseases International and the NGO Committee for Rare Diseases.


More links


Finding a support group is important

A rare disease can be isolating for the patient as well as for the caregiver, especially when it’s your child who has the condition.

Connecting with others can be essential, not only for support but also to share information and resources.