Breaking News
April 27, 2018 - Alcohol Intake May Influence Oral Microbiome Composition
April 27, 2018 - What happens to our muscles during spaceflight and when living on Mars?
April 27, 2018 - Abdominal pain should be seen as a warning sign for invasive meningococcal disease
April 26, 2018 - Mediterranean diet enhances good bacteria living in the gut
April 26, 2018 - UA researchers aim to predict and prevent fatal disease in premature babies
April 26, 2018 - Researchers develop new method for early and accurate breast cancer screening
April 26, 2018 - Cytochalasin B-induced membrane vesicles successfully tested as vector for anti-tumor drug delivery
April 26, 2018 - Hospitals lure diabetes patients with self-care courses, but costs can weigh heavily
April 26, 2018 - Common therapy options for psoriasis can help reduce coronary plaque, study shows
April 26, 2018 - Kids Are Naturally as Fit as an ‘Iron Man’
April 26, 2018 - Traditional health claims about India’s ayurvedic foods help make them big business
April 26, 2018 - Maternal binge drinking may make offspring more vulnerable to mood problems and alcohol abuse
April 26, 2018 - VA hospitals provide better quality care than other health providers
April 26, 2018 - Cytosurge develops new 3D printing method that allows scientists to manufacture tiny, complex metal components
April 26, 2018 - Detailed genetic testing of head and neck cancers could lead to more personalized treatments
April 26, 2018 - Study shows new approach to improve survival rates for patients with stage IV Wilms tumors
April 26, 2018 - Nonsurgical technique enables people with spinal cord injuries to regain use of hands
April 26, 2018 - Elective induction of labor at 39 weeks decreases risks of C-section, other complications
April 26, 2018 - Hair products used by Black women contain dozens of hazardous chemicals
April 26, 2018 - Scientists create an atlas of the human genome
April 26, 2018 - New shape of DNA found in human cells
April 26, 2018 - Researchers target telomerase for killing NRAS-mutant melanoma cells
April 26, 2018 - Scientists improve growth of 3d brain models to better understand autism, dementia, schizophrenia
April 26, 2018 - Evox Therapeutics expands into new facilities at The Oxford Science Park
April 26, 2018 - Scientists discover new method for measuring cellular age
April 26, 2018 - UNC-Chapel Hill receives new award to help improve health of North Carolinians
April 26, 2018 - Study finds no evidence of chronic wasting disease transmissibility in macaques
April 26, 2018 - Study highlights impact of early detection on skin cancer survival
April 26, 2018 - Scientists discover culprit in reducing effectiveness of insulin
April 26, 2018 - Exploiting rabies virus machinery to usher Parkinson’s disease drug directly to the brain
April 26, 2018 - ‘Rapid autopsy’ programs seek clues to cancer within hours of death
April 26, 2018 - Personalised prescriptions according to your genetics
April 26, 2018 - ECDC analysis highlights measles vaccination gaps in teenagers and young adults
April 26, 2018 - Study assesses link between cognitive function levels and crash risk among older drivers
April 26, 2018 - Researchers uncover how obesity leads to cancer initiation
April 26, 2018 - Consuming large quantities of sugar during pregnancy can affect child’s cognition, shows study
April 26, 2018 - Researchers create new tool to measure patient uncertainty for predicting hospital readmissions
April 26, 2018 - FDA Alert: Lamictal (lamotrigine): Drug Safety Communication
April 26, 2018 - Massive single-cell survey of kidney cell types reveals new paths to disease
April 26, 2018 - Cognitive behavioral therapy can help children with autism manage emotional challenges
April 26, 2018 - CU Anschutz Medical Campus receives NIH grant to speed up discovery of new treatments
April 26, 2018 - Researchers discover significant distortions in leading genetics study method
April 26, 2018 - New combination therapy could improve survival in children with high-risk neuroblastoma
April 26, 2018 - Scientists clarify casual role of oxidative stress in metabolically abnormal and healthy obesities
April 26, 2018 - Home-based exercise program found ineffective for patients with peripheral artery disease
April 26, 2018 - Surgeries performed by older surgeons have lower patient mortality rates, study reveals
April 26, 2018 - New UCLA study could elucidate certain causes of infertility and miscarriage
April 26, 2018 - Choroidal Thickness Changes in Patients With Untreated DM
April 26, 2018 - Medical chemists discover peptic ulcer treatment metallodrug effective in ‘taming’ superbugs
April 26, 2018 - UB researchers build 3D-printed, drug-filled dentures to fight against infections
April 26, 2018 - Researchers find role of iron storage gene in slowing down prostate cancer growth
April 26, 2018 - Study suggests link between regular mid-day naps and neurocognitive function in teens
April 26, 2018 - Researchers gain ground-breaking insights into how inflammatory diseases work
April 26, 2018 - Injured U.S. Vet Receives World’s First Penis/Scrotum Transplant
April 26, 2018 - Researchers find existing drug effective at preventing onset of type 1 diabetes
April 26, 2018 - MGH researchers identify risk factors for drug overdose in youth with substance use disorders
April 26, 2018 - Researchers develop new vaccine to help people overcome bath salts abuse
April 26, 2018 - Genetic signature predicts diabetes diagnosis
April 26, 2018 - Study shows link between restless legs syndrome symptoms and brain structure
April 26, 2018 - MU researchers use new techniques to fight against diabetic retinopathy
April 26, 2018 - AAE’s new practice statements aim at improving patient care
April 26, 2018 - Expression of long non-coding RNAs can result in high levels of specific proteins involved in cancer
April 26, 2018 - FDA re-examining safety of new drug approved for Parkinson’s disease psychosis
April 26, 2018 - Unanimous Positive Result of FDA Advisory Committee Meeting for First Plant-Based Pharmaceutical Cannabidiol Treatment for Seizures in Patients with Two Rare, Severe Forms of Epilepsy
April 26, 2018 - Bacteria boost antifungal drug resistance in severe childhood tooth decay
April 26, 2018 - New study affirms bedtime habits of Americans
April 26, 2018 - Hospital patients are more interested in tracking their health data, research shows
April 26, 2018 - Study shows gene variations associated with malaria risk
April 26, 2018 - Inhealthcare teams up with MSKassist to combat problems related to obesity and aging
April 26, 2018 - Caffeine during pregnancy – babies 66 percent more likely to become overweight
April 26, 2018 - FDA Approves Jynarque (tolvaptan) to Slow Kidney Function Decline in Rapidly Progressing Autosomal Dominant Polycystic Kidney Disease
April 26, 2018 - Pricey dental implants often best but insurance rarely pays
April 26, 2018 - Advion’s Peak Express software now available with the expression compact mass spectrometer
April 25, 2018 - Researchers find link between pneumonia in older people and PPI prescriptions
April 25, 2018 - Alcohol damages microbiome in the mouth
April 25, 2018 - Regular soaking in hot tub improves health outlook in obese women with PCOS
April 25, 2018 - FDA Alert: Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) Devices: Letter to Health Care Providers
April 25, 2018 - Sunshine could hold clues on the timing for a severe form of heart attack, study says
April 25, 2018 - Sartorius Stedim Biotech launches mini bioreactor vessel for ambr 250 high throughput system
April 25, 2018 - Biofeedback-assisted relaxation may help children during medical procedures
Sarepta Therapeutics Announces Plan to Submit a New Drug Application (NDA) for Accelerated Approval of Golodirsen (SRP-4053) in Patients with Duchenne Muscular Dystrophy (DMD) Amenable to Skipping Exon 53

Sarepta Therapeutics Announces Plan to Submit a New Drug Application (NDA) for Accelerated Approval of Golodirsen (SRP-4053) in Patients with Duchenne Muscular Dystrophy (DMD) Amenable to Skipping Exon 53

image_pdfDownload PDFimage_print

golodirsen

Treatment for Muscular Dystrophy

Sarepta Therapeutics Announces Plan to Submit a New Drug Application (NDA) for Accelerated Approval of Golodirsen (SRP-4053) in Patients with Duchenne Muscular Dystrophy (DMD) Amenable to Skipping Exon 53

CAMBRIDGE, Mass., March 12, 2018 (GLOBE NEWSWIRE) — Sarepta Therapeutics, Inc. (NASDAQ:SRPT), a commercial-stage biopharmaceutical company focused on the discovery and development of precision genetic medicine to treat rare neuromuscular diseases, announced today that it recently received final minutes from a February 2018 Type C meeting held with the Division of Neurology Products, United States Food and Drug Administration (the Division), to solicit the Division’s guidance on the development pathway for Sarepta’s therapeutic candidate, golodirsen, a phosphordiamidate morpholino oligimer engineered to treat those patients with Duchenne muscular dystrophy (DMD) who have genetic mutations subject to skipping exon 53 of the DMD gene.

“Sarepta is thankful for the FDA Neurology Division’s thoughtful and direct guidance regarding golodirsen,” said Doug Ingram, Sarepta’s president and chief executive officer. “Obviously, whether golodirsen will obtain accelerated approval is a review decision that will come after the submission and review of our NDA. But we greatly appreciate the willingness of the Neurology Division to engage and provide clear direction to us on the steps necessary to support an NDA submission for accelerated approval.”

As previously announced in the third quarter of 2017, Sarepta’s 4053-101 study – a Phase 1/2 study to assess the safety, tolerability, pharmacokinetics and efficacy of golodirsen in 25 boys with confirmed deletions of the DMD gene amenable to exon 53 skipping – demonstrated statistically significant results in favor of golodirsen on all biological endpoints, including properly exon-skipped RNA transcript using reverse transcription polymerase chain reaction, quantity of dystrophin expression using Western blot and dystrophin intensity pursuant to immunohistochemistry.

Based on the results of Study 4053-101 and informed now by FDA’s feedback, Sarepta intends to complete a rolling submission of a golodirsen NDA by year-end 2018, seeking accelerated approval of golodirsen based on an increase in dystrophin protein as a surrogate endpoint.

Among other guidance:

The Division reported that in light of the precedent of eteplirsen’s approval, based on an increase in dystrophin protein as a surrogate endpoint reasonably likely to predict clinical benefit, a statistically significant increase in de novo, truncated dystrophin protein in Study 4053-101, based on a scientifically sound experimental design and rigorous analytical methods, may serve as a basis for accelerated approval of golodirsen for the treatment of Duchenne muscular dystrophy, assuming that Sarepta provides substantial evidence of the effect of golodirsen on dystrophin from a single study.

Sarepta proposed that its Study 4045-301 (ESSENCE), a Phase 3 ongoing placebo-controlled clinical trial assessing the efficacy of golodirsen and casimersen, serve as the post-marketing confirmatory study. The Division confirmed that ESSENCE could possibly serve as a confirmatory study if golodirsen is granted accelerated approval, with the understanding that it is incumbent upon Sarepta to describe how it will successfully enroll and complete the ESSENCE study in light of an accelerated approval.

The Division indicated that it is willing to accept a rolling submission of the NDA. The complete submission must include long-term animal toxicology studies, which will be completed in the fourth quarter of 2018. Hence, Sarepta anticipates the NDA submission will be complete in late 2018.

About Golodirsen

Golodirsen uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 53 of the DMD gene. Golodirsen is designed to bind to exon 53 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 53 skipping. Exon skipping is intended to allow for production of an internally truncated but functional dystrophin protein.

Golodirsen is one of the investigational candidates currently being evaluated in the ESSENCE study, a global, randomized double-blind, placebo-controlled study evaluating efficacy and safety in patients amenable to skipping exons 45 or 53.

Dystrophin is a protein found in muscle cells that, while present in extremely small amounts (about 0.002 percent of total muscle protein), is crucial in strengthening and protecting muscle fibers. 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 fiber function. Progressive muscle weakness in the lower limbs spreads to the arms, neck and other areas of the body. The condition is universally fatal, and death usually occurs before the age of 30 generally due to respiratory or cardiac failure.

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.

About Sarepta Therapeutics

Sarepta Therapeutics is a commercial-stage biopharmaceutical company focused on the discovery and development of precision genetic medicine to treat rare neuromuscular diseases. The Company is primarily focused on rapidly advancing the development of its potentially disease-modifying Duchenne muscular dystrophy (DMD) drug candidates. For more information, please visit www.sarepta.com.

Sarepta Forward-Looking Statements

This press release contains “forward-looking statements”. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “will,” “intends,” “potential,” “possible” and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements regarding Sarepta’s plan to submit an NDA for accelerated approval of golodirsen in patients with DMD who are amenable to exon 53 skippingbased on an increase in dystrophin protein as a surrogate endpoint; Sarepta’s intention to complete a rolling NDA submission for golodirsen by year-end 2018; the possibility of a statistically significant increase in de novo, truncated dystrophin protein in Study 4053-101 based on a scientifically sound experimental design and rigorous analytical methods to serve as a basis for accelerated approval of golodirsen for the treatment of DMD; the ability to demonstrate substantial evidence of the effect of golodirsen on dystrophin using a single study; the possibility of the ESSENCE study to serve as a confirmatory study if golodirsen is granted accelerated approval;the possibility of the FDA accepting our rolling NDA submission; our ability to complete toxicology studies in the fourth quarter of 2018;the possibility of receiving accelerated approval for golodirsen; golodirsen’s potential to bind to exon 53 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 53 skipping; and exon skipping’s intention to allow for production of an internally truncated but functional dystrophin protein.

These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta’s control. Known risk factors include, among others: there may be delays in completing the NDA submission and Sarepta may not be able to submit the NDA on time or at all for various reasons, including any negative or inconsistent safety and efficacy data and regulatory, court or agency decisions;Sarepta may not be able to complete clinical trials required by the FDA or other regulatory authorities for approval of golodirsen; golodirsen may not result in a viable treatment suitable for commercialization due to a variety of reasons including the results of future research may not be consistent with past positive results or may fail to meet regulatory approval requirements for the safety and efficacy of product candidates; and even if golodirsen results in a commercialized product, Sarepta may not achieve any significant revenues from the sale of such product; and those risks identified under the heading “Risk Factors” in Sarepta’s most recent Annual Report on Form 10-K for the year ended December 31, 2017 and other Securities and Exchange Commission (SEC) filings made by the Company which you are encouraged to review.

Any of the foregoing risks could materially and adversely affect the Company’s business, results of operations and the trading price of Sarepta’s common stock. For a detailed description of risks and uncertainties Sarepta faces, you are encouraged to review Sarepta’s 2017 Annual Report on Form 10-K filed with the SEC as well as other SEC filings made by Sarepta. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof.

Source: Sarepta Therapeutics, Inc.

Posted: March 2018

golodirsen FDA Approval History

Tagged with:

About author

Related Articles