The Story of the Foundation to Eradicate Duchenne
January 2, 2024
Data from international public/private partnership leads to the first therapy for Duchenne muscular dystrophy approved by both EMA and FDA.
- AGAMREE®(vamorolone) oral suspension is the first pharmacological intervention in Duchenne muscular dystrophy (DMD) to demonstrate robust evidence of efficacy via a randomized, double-blind, placebo-controlled clinical trial.
- The robust and compelling data supporting approval of AGAMREE in both the EU (EMA) and US (FDA) resulted from a broad international public/private participation model, involving government agencies, over a dozen non-profit foundations, an established international academic clinical trial network (CINRG; TRiNDS), and ReveraGen BioPharma Inc spanning over 13 years.
The EMA approved AGAMREE (vamorolone) for Duchenne muscular dystrophy (DMD), ages 4 years and older on 18 December 2023. The US FDA previously approved AGAMREE for DMD (26 October 2023). This makes AGAMREE the first pharmacological intervention poised to receive full approval for DMD populations in both the US and EU.
AGAMREE was developed utilizing an innovative public and private participation model with central governments, non-profit foundations and commercial stage research and development organizations working in coordination to advance the development program from discovery through clinical trials all the way to drug approval.
Patient-focused foundations including the Muscular Dystrophy Association (USA), Parent Project Muscular Dystrophy foundation (USA), Joining Jack (UK), DRF (UK) and Duchenne Children’s Trust (UK)), under venture philanthropy models (shared risk, shared benefit) provided financial support for specific development activities. Further investments in the form of licensing and milestone payments by Actelion, Idorsia, and Santhera provided key additional resources to complete the AGAMREE development program.
The US Department of Defense through the Congressionally Directed Medical Research Programs (CDMRP) funded research for early drug discovery, clinical outcomes research, and natural history studies by the Cooperative International Neuromuscular Research Group. The National Institutes of Health helped de-risk the non-clinical program by completing robust confirmatory efficacy studies and implementing an improved synthetic process for drug manufacturing (National Center for Advancing Translational Sciences – TRND program) and supported clinical trials (National Institute of Neurological Disorders and Stroke – SBIR program). The European Commission provided a Horizons 2020 grant for the clinical trial program through Newcastle University in the UK.
“The overall AGAMREE program leveraged infrastructure for drug development and clinical trials in DMD, with extensive peer review and feedback at each step of the development pipeline,” said Dr. Eric Hoffman, CEO, and co-founder of ReveraGen. “A broad swath of the international stake holders and the academic research community has been intimately involved with bringing AGAMREE to approval,” Dr. Hoffman continued.
“The Cooperative International Neuromuscular Research Group (CINRG) and the TRiNDS coordinating center brought extensive disease-specific expertise to the clinical trial program,” said Dr. Paula Clemens, Professor of Neurology at the University of Pittsburgh, and Study Chair of the Phase 2a and Phase 2b clinical trials. “Without the extensive outcomes research and collaborative structure of the CINRG group, obtaining the robust data from the AGAMREE trials would likely not have been possible,” Dr. Clemens noted.
A key aspect of de-risking of the AGAMREE program was de-risking in the early pre-clinical space. “One reason for the program’s success is robust foundational preclinical in vitro, and in vivo data using well-standardized outcome measures that our laboratories have developed over the last two decades in collaboration with the international TREAT-NMD network,” said Dr. Kanneboyina Nagaraju co-founder of ReveraGen, and Dean of the School of Pharmacy and Pharmaceutical Sciences, Binghamton University – State University of New York.
Dr. Jesse Damsker, COO of ReveraGen said, “I believe the compelling data of vamorolone efficacy and safety through the clinical trials, and extensive and successful inspections by both FDA and EMA of our clinical trial program, is a testament to the highly collaborative team and supporting expert CROs.” The flexibility of the vamorolone clinical team to respond to the COVID-19 pandemic was aided by the very small central group coordinating the studies, and rapid and effective communications with the FDA. “I’ve worked in major pharma for many decades, and working with this small ReveraGen team and their collaborative network is one of the best examples of efficiency and adaptability I’ve seen in the drug development space,” said Dr. John McCall, VP for Chemistry and co-founder of ReveraGen.
“The Foundation to Eradicate Duchenne has been a participant in the AGAMREE project since the beginning, and I am delighted to see AGAMREE be approved,” said Joel Wood, President, and CEO of the foundation.
“Children’s National Hospital was the initial home for early vamorolone research, and ReveraGen the first spin-off company,” said Mark Batshaw, M.D., distinguished investigator in the Center for Genetic Medicine Research at Children’s National. “The EMA and FDA approval underscores the importance of supporting clinicians and researchers who are developing solutions to advance healthcare for children.
“We are delighted that proceeds from the future sales of AGAMREE will be shared with over a dozen non-profit foundations, continuing the shared risk – shared benefit agreements between ReveraGen and these foundations,” noted Dr. Hoffman. Significant portions of the proceeds from sales-based milestone payments and dividends that are anticipated to be coming to ReveraGen as a result of licensing the product will be distributed to non-profits based on sales of AGAMREE.
About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a rare inherited X-chromosome-linked disease, which almost exclusively affects males. DMD is characterized by inflammation which is present at birth or shortly thereafter. Inflammation leads to fibrosis of muscle and is clinically manifested by progressive muscle degeneration and weakness. Major milestones in the disease are the loss of ambulation, the loss of self-feeding, the start of assisted ventilation, and the development of cardiomyopathy. Corticosteroids are the current standard of care for the treatment of DMD.
About ReveraGen BioPharma Inc.
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 USA, Parent Project Muscular Dystrophy, Foundation to Eradicate Duchenne, Save Our Sons, JoiningJack, Action Duchenne, CureDuchenne, Ryan’s Quest, Alex’s Wish, DuchenneUK, Pietro’s Fight, Michael’s Cause, Duchenne Research Fund, and Defeat Duchenne Canada. 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). www.reveragen.com
This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs and the Defense Health Agency J9, Research and Development Directorate, or the U.S. Army Medical Research Acquisition Activity at the U.S. Army Medical Research and Development Command. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.
June 1, 2021
Santhera and ReveraGen Announce Positive and Statistically Highly Significant Topline Results with Vamorolone in Pivotal VISION-DMD Study
Vamorolone demonstrates strong efficacy across primary and secondary endpoints in both doses of 6 mg/kg/day and 2 mg/kg/day
Primary endpoint Time to Stand (TTSTAND) velocity is met for vamorolone 6 mg/kg/day versus placebo (p=0.002)
Secondary endpoints for Six-Minute Walk (6MWT) and Time to Run/Walk 10 meters (TTRW) tests achieve statistical significance versus placebo
Study confirmed good safety and tolerability profile of vamorolone for both doses
Santhera plans to file a New Drug Application (NDA) with the US FDA in Q1-2022, requesting priority review
Pratteln, Switzerland, and Rockville, MD, USA, June 1, 2021 – Santhera Pharmaceuticals (SIX: SANN) and ReveraGen BioPharma, Inc (US: private) announce positive key results from the VISION-DMD study, demonstrating robust efficacy across multiple efficacy endpoints and favorable safety and tolerability of vamorolone in the treatment of patients with DMD.
VISION-DMD is a pivotal Phase 2b study designed to demonstrate efficacy and safety of vamorolone compared to placebo and prednisone (active control) in the treatment of DMD. In the first 24-week double-blind period, of which the topline data readout is presented here, 121 ambulant boys aged 4 to <7 years with DMD were randomized to receive vamorolone (low dose 2 mg/kg/day or high dose 6 mg/kg/day) or prednisone (0.75 mg/kg/day) or placebo. A second period of 24 weeks, where all participants receive vamorolone treatment on either of the two dose levels, will continue to capture additional longer term safety and tolerability data.
Vamorolone demonstrates efficacy across primary and secondary endpoints and over a broad dose range
The study met its primary endpoint of superiority in change of time to stand from supine positioning to standing (TTSTAND) velocity with vamorolone 6 mg/kg/day versus placebo (p=0.002) with a treatment difference of 0.06 [95% CI: 0.02–0.10] rises/second from baseline. This corresponds to a clinically relevant improvement in TTSTAND in the vamorolone 6 mg/kg/day group from 6.0 to 4.6 seconds and a corresponding deterioration in the placebo group from 5.4 to 5.5 seconds. The study also demonstrated superiority of vamorolone versus placebo across multiple secondary endpoints which include (in the order of pre-defined hierarchy): TTSTAND velocity for 2 mg/kg/day (p=0.02), 6MWT for 6 mg/kg/day (p=0.003) and 2 mg/kg/day (p=0.009), TTRW for 6 mg/kg/day (p=0.002). The clinical results establish the efficacy of vamorolone over a wide, threefold dose range from 2 to 6 mg/kg/day. No statistically significant differences were observed between vamorolone 6 mg/kg/day and prednisone across the above endpoints.
Vamorolone showed a favorable safety and tolerability profile over prednisone
The study completion rate at 24 weeks was 94% (or 114 of 121 participants). Vamorolone at both doses of 2 and 6 mg/kg/day showed a favorable safety and tolerability profile. In the vamorolone groups, no grade 3 or higher treatment emergent adverse events (TEAEs) or adverse events leading to study discontinuation were observed. The total number of TEAEs was lower in the vamorolone 2 mg/kg/day (events n=96) and 6 mg/kg/day (n=91) groups compared to prednisone (n=120). In a prespecified analysis of clinically relevant adverse events (moderate, severe, serious or leading to discontinuation due to safety), defined for the EMA and conducted by Santhera, vamorolone 6 mg/kg/day was significantly superior to prednisone (n=6 vs n=19, p=0.02).
As previously published, in open-label studies of 2.5 years duration (113 patient years), vamorolone did not show stunting of growth as reported with conventional corticosteroids. Particularly noteworthy, this was validated in the current 24-week double-blind study where vamorolone 6 mg/kg/day versus prednisone 0.75 mg/kg/day showed a significant difference in growth velocity (p=0.02). “Stunting of growth is a major concern of families and patients treated with corticosteroids, and we are delighted to see this superiority of vamorolone proven in this double-blind study,” said Paula Clemens, MD, study Co-Chair, and Vice Chair of VA Affairs and Professor of Neurology, University of Pittsburgh School of Medicine.
“Today’s news is a tremendous milestone for patients and Santhera as we further advance vamorolone as a foundational treatment option in DMD. The treatment effect translates into the potential to delay disease progression by about two years and indicates disease modifying potential of vamorolone,” said Dario Eklund, Chief Executive Officer of Santhera. “We now look forward to working with regulatory authorities to bring vamorolone to DMD patients, first in the US and subsequently in Europe.
“We are thrilled about the positive results of the VISION-DMD study as it represents a culmination over a decade of scientific research,” said Eric Hoffman, PhD, President and CEO at ReveraGen BioPharma and Professor of Pharmaceutical Sciences, Binghamton University – State University of New York. “We are grateful to have been able to gather such important data and would like to thank all VISION-DMD participants, their families and caregivers, as well as investigators and study personnel, for their commitment to this ongoing program.”
“The strength of evidence for both efficacy and safety of vamorolone over such a wide dose range from 2 to 6 mg/kg/day allows clinicians to individually tailor treatment of Duchenne patients by starting at the higher 6 mg/kg/day dose of vamorolone with equivalent efficacy to daily prednisone and titrate the dose according to how well the treatment is tolerated whilst maintaining optimal efficacy. I am enthusiastic that this approach may allow patients to avoid side effects that currently lead to discontinuing steroid treatment, meaning they are able stay on for longer,” said Craig McDonald, MD, Professor and Chair, Department of Physical Medicine & Rehabilitation and Director of Neuromuscular Disease Clinics, UC Davis Health, USA.
Santhera plans to submit a New Drug Application (NDA) in the US in Q1-2022, requesting a priority review based on the fast track designation granted by the FDA. The VISION-DMD study continues to 48 weeks and will, subject to a positive outcome, deliver data for the submission of a marketing authorization application in Europe in Q2-2022. Upon approval, Santhera intends to commercialize vamorolone for the treatment of DMD through its own organization in the United States and main markets in Europe, and is seeking collaborations outside those regions for DMD and for additional indications worldwide. Santhera estimates the peak sales potential for vamorolone in the indication DMD alone to be in excess of USD 500 million in the US and the largest five European countries combined.
Vamorolone has been granted Orphan Drug status in the US and in Europe, and has received Fast Track and Rare Pediatric Disease designations by the US FDA and Promising Innovative Medicine (PIM) status from the UK MHRA. On September 2, 2020, Santhera signed agreements with ReveraGen and Idorsia that granted Santhera an exclusive license to vamorolone for all indications worldwide.
Santhera will hold a conference call with webcast today at 16:00 CEST / 15:00 BST / 10:00 EDT to discuss the vamorolone study results. Participants are invited to join either the webcast or conference call 5-10 minutes before the start. Questions will only be taken from participants on the conference call.
Webcast: click here http://public.viavid.com/index.php?id=145140
Conference call: dial one of the following numbers (Conference ID 13720219):
Toll Free: +1-877-407-9716
Replay: a webcast replay of the conference will be available shortly after the call at the above link. Slides: the slide presentation will be available after the webcast at https://www.santhera.com/investors-and-media/news-and-media-center/company-presentations.
VISION-DMD is a 48-week Phase 2b study designed as a pivotal trial to demonstrate efficacy and safety of vamorolone (2 and 6 mg/kg/day) versus prednisone (0.75 mg/kg/day) and placebo in 121 ambulant boys aged 4 to <7 years with Duchenne muscular dystrophy (DMD). The topline results cover data from the first period of 24 weeks of the study where vamorolone is compared to placebo (FDA-prerequisite for filing an NDA) and prednisone. The primary endpoint of the study is TTSTAND velocity at 24 weeks comparing the 6 mg/kg/day dose of vamorolone to placebo. TTSTAND velocity measures the speed at which patients are able to stand up from lying in a supine position and is a strong and recognized marker for muscle function. Secondary efficacy outcome measures include TTSTAND velocity for vamorolone at the lower dose of 2 mg/kg/day, Six-Minute Walk (6MWT) and Time to Run/Walk 10 meters (TTRW) tests at 24 weeks. The VISION-DMD study continues to completion at 48 weeks. During the second period of this 48-week study, all participants receive vamorolone. Participants from the placebo and prednisone arms are randomized to either the 2 or 6 mg/kg/day dose of vamorolone and the current vamorolone arms continue on their existing dose. The final data readout is expected in Q4-2021. In addition to efficacy, the study aims to confirm the favorable tolerability profile of vamorolone with the potential to offer an alternative to current standard of care. Although glucocorticoids are part of the current care recommendations for DMD, their adverse effect profile limits their use.
Vamorolone is a first-in-class dissociative steroid which retains the anti-inflammatory activity of corticosteroids while decreasing the deleterious side effects. As such, vamorolone could emerge as a promising alternative to existing corticosteroids, the current standard of care in children and adolescent patients with DMD. There is substantial unmet medical need in this patient group as high-dose corticosteroids have significant systemic side effects that diminish patient quality of life.
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.
About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a rare inherited X-chromosome-linked disease, which almost exclusively affects males. DMD is characterized by inflammation which is present at birth or shortly thereafter. Inflammation leads to fibrosis of muscle and is clinically manifested by progressive muscle degeneration and weakness. Major milestones in the disease are the loss of ambulation, the loss of self-feeding, the start of assisted ventilation, and the development of cardiomyopathy. DMD reduces life expectancy to before the fourth decade due to respiratory and/or cardiac failure.
Santhera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative medicines for rare neuromuscular and pulmonary diseases with high unmet medical need. Santhera has an exclusive license for all indications worldwide to vamorolone, a first-in-class dissociative steroid with novel mode of action, which was investigated in a pivotal study in patients with DMD as an alternative to standard corticosteroids. The clinical stage pipeline also includes lonodelestat (POL6014) to treat cystic fibrosis (CF) and other neutrophilic pulmonary diseases as well as an exploratory gene therapy approach targeting congenital muscular dystrophies. Santhera out-licensed ex-North American rights to its first approved product, Raxone® (idebenone), for the treatment of Leber’s hereditary optic neuropathy (LHON) to Chiesi Group. For further information, please visit www.santhera.com.
Raxone® is a trademark of Santhera Pharmaceuticals.
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 USA, Parent Project Muscular Dystrophy, Foundation to Eradicate Duchenne, Save Our Sons, JoiningJack, Action Duchenne, CureDuchenne, Ryan’s Quest, Alex’s Wish, DuchenneUK, Pietro’s Fight, Michael’s Cause, Duchenne Research Fund, and Jesse’s Journey. 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). www.reveragen.com
For further information please contact:
Santhera Pharmaceuticals Holding AG, Hohenrainstrasse 24, CH-4133 Pratteln
Eva Kalias, Head External Communications
Phone: +41 79 875 27 80
Eric Hoffman, PhD, President and CEO
Phone: + 1 240-672-0295
Disclaimer / Forward-looking statements
This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Santhera Pharmaceuticals Holding AG. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements.
June 2, 2020
ReveraGen BioPharma Completes 2.5 Years Vamorolone Treatment of 41 Duchenne Muscular Dystrophy Boys
Rockville, MD –
Vamorolone is a first-in-class daily oral drug being developed to improve muscle function in Duchenne muscular dystrophy. Vamorolone has multiple mechanisms of action shown by published pre-clinical studies, including potent anti-inflammatory activities, cardioprotective activity, promotion of membrane repair, and synchronization of cell repair. While a steroidal drug, pre-clinical and clinical data has shown that vamorolone may lack multiple safety concerns of corticosteroidal anti-inflammatories, such as deflazacort and prednisone, while adding novel aspects of potential efficacy such as mineralocorticoid antagonism.
In 2016-2017, 48 DMD boys (age 4 to <7 years) entered a series of pharmacokinetics, safety and dose-finding efficacy studies (VBP15-002; VBP15-003). After 6-months of treatment, the DMD participants and their families were given the option to transition to standard of care (deflazacort or prednisone), or remain on vamorolone via a 2-year long-term extension study (VBP15-LTE). Of the 46 DMD boys completing the 6-month dose-ranging study, all (100%) requested to continue vamorolone treatment in the long-term extension, rather than transition to corticosteroids. The last participant, last visit of VBP15-LTE occurred in April 2020, with 41 of 46 DMD boys completing the full 2-year treatment period. The large majority of the 41 DMD boys completing the 2-year LTE have transitioned to Expanded Access Program (USA, Canada, Israel), or compassionate use programs (UK, Sweden, Australia).
“Parents and their physicians seem to be satisfied with vamorolone, as nearly all wish to continue vamorolone treatment,” said Paula Clemens, MD, Professor at the University of Pittsburgh School of Medicine, and Study Chair. The long-term extension study enabled dose escalation and de-escalation at the preference of the physician and family (suggested range 2.0 to 6.0 mg/kg/day). Of those 41 participants completing the 2-year end-of-study visit, 27 ended at 6.0 mg/kg/day (66%), 11 at 2.0 mg/kg/day (27%), and 3 at 4.0 mg/kg/day (7%). Thus, the majority (2/3) of physicians/families chose treatment at the highest tested dose of vamorolone by the end of the LTE study (6.0 mg/kg/day).
“With most participants continuing treatment with vamorolone long-term, we have assembled a strong safety database, with 106 patient-years of vamorolone exposure in DMD boys, with no serious adverse events attributable to vamorolone to date,” said Eric Hoffman, PhD, Vice President of Research at ReveraGen BioPharma.
A registration trial, VBP15-004, is ongoing with 103 of 128 DMD participants enrolled. Enrollment is expected to complete soon, with 6-month read-out for FDA NDA submission in 4Q2020 or 1Q2021. Information on the VBP15-004 trial can be obtained from Suzanne Gaglianone (Suzanne.firstname.lastname@example.org) or Andrea D’Alessandro (email@example.com).
Eric Hoffman. Email: firstname.lastname@example.org
About Duchenne muscular dystrophy
Duchenne muscular dystrophy is a rare genetic disease that predominantly affects young boys. Loss of the large protein, dystrophin, in muscle leads to persistent damage to muscle. DMD is a progressive disease, with gradual loss of muscle and weakness over 20 years leading to loss of walking abilities, and shortened lifespan.
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 USA, Parent Project Muscular Dystrophy, Foundation to Eradicate Duchenne, Save Our Sons, JoiningJack, Action Duchenne, CureDuchenne, Ryan’s Quest, Alex’s Wish, DuchenneUK, Pietro’s Fight, Michael’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). www.reveragen.com.
Vamorolone is a first-in-class drug candidate that binds to the same receptors as corticosteroids but modifies the downstream activity of the receptors [1,2]. 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 significant unmet medical need in this patient group as high dose corticosteroids have severe systemic side effects that detract from patient quality of life. Phase 1 studies in adult volunteers , and Phase 2a studies in 48 DMD boys  showed biomarker studies consistent with a partial agonist mechanism of action, with dose-responsive improvements in both efficacy and safety biomarkers. Dose-finding studies with 24-weeks of vamorolone treatment over a dose range of 0.25 to 6.0 mg/kg/day showed dose-related improvements in multiple measures of muscle strength and endurance . Vamorolone has been granted Orphan Drug status by both FDA and EMA, Fast Track designation by the FDA, and Priority Innovative Medicine designation by the UK MHRA. In November 2018, Santhera acquired from Idorsia Pharmaceuticals Ltd (SIX: IDIA), who has an option to an exclusive, worldwide license to vamorolone, the option to an exclusive sub-license to vamorolone in all indications and all countries worldwide, except Japan and South Korea.
About the Cooperative International Neuromuscular Research Group (CINRG)
CINRG was founded in 2000 as an international academic clinical trial network, with a focus on pediatric neuromuscular disease. CINRG has enrolled over 1,500 patients into clinical research studies. Recent studies include the CINRG Duchenne Natural History Study (DNHS) with 440 DMD patients and over 100 healthy peers followed by expert neuromuscular physicians in 20 sites in 10 countries. See www.cinrgresearch.org www.trinds.com
May 26, 2020
NS Pharma Announces Publication of Clinical Trial Data for Viltolarsen in DMD Patients in JAMA Neurology
PARAMUS, NJ –
NS Pharma, Inc. (NS Pharma; President, Tsugio Tanaka), a wholly owned subsidiary of Nippon Shinyaku Co., Ltd. (Nippon Shinyaku; President Shigenobu Maekawa), announced today that JAMA Neurology has published results from a clinical trial of viltolarsen, an investigational agent being evaluated in Duchenne muscular dystrophy (DMD) patients who are amenable to exon 53 skipping therapy.
“In this study, 100% of patients were shown to have more dystrophin after treatment with viltolarsen and 88% achieved dystrophin levels of greater than 3%,” said lead study author and investigator Paula Clemens, MD, University of Pittsburgh School of Medicine. “These increases were seen in patients as young as four years of age and after six months or less of treatment, which underscores the impressive results seen in this study.”
This Phase 2, two-period, dose-finding study enrolled 16 DMD patients, from four to less than 10 years of age, who were amenable to exon 53 skipping therapy. Study participants were randomized to two doses of viltolarsen (40 mg/kg/wk and 80 mg/kg/wk) for 20 to 24 weeks. At the end of the study, treatment with viltolarsen was associated with statistically significant increases in mean dystrophin expression (40 mg/kg/wk: p<0.001; 80 mg/kg/wk p=0.012). Mean dystrophin levels of 5.7% and 5.9% were observed in comparison to mean baseline levels of 0.3% and 0.6% in the 40 mg/kg/wk and 80 mg/kg/wk groups, respectively. Fourteen out of 16 patients (88%) reached dystrophin levels greater than 3%.
The most common treatment emergent adverse events occurring in greater than one patient were: cold, cough, nasal congestion, bruising, joint pain, diarrhea and vomiting. No serious adverse events were observed in the study.
“Lack of functional dystrophin is recognized as the singular underlying cause of the devastating impact of DMD,” said study author and investigator Vamshi Rao, MD, Ann & Robert H. Lurie Children’s Hospital of Chicago. “As a pediatric neurologist who specializes in the treatment of DMD, I am encouraged by the dystrophin increases observed in this study and the potential of viltolarsen to address the underlying cause of DMD.”
“This is one of the first studies of exon skipping therapies in DMD to generate rigorous data on the primary biomarker of dystrophin protein,” said study author Eric Hoffman, PhD, Associate Dean for Research and Professor of Pharmaceutical Sciences at Binghamton University. “Having assisted in the development of viltolarsen for many years, and decades more researching the genetics and genomics of DMD, I am pleased by the results of this study and the implications for families facing DMD.”
Viltolarsen has not yet been approved in the U.S. and its New Drug Application was recently granted Priority Review by the FDA with an anticipated action date in the third quarter of 2020. In March 2020, viltolarsen was approved in Japan for the treatment of DMD patients amenable to exon 53 skipping therapy.
“We are deeply committed to the development of viltolarsen and offering healthier futures to DMD patients and families,” said Tsugio Tanaka, President, NS Pharma, Inc. “Based on these results we are optimistic that, if it is approved, viltolarsen will become an important new treatment option for DMD patients and healthcare providers.”
NS Pharma continues to study the safety and efficacy of viltolarsen in the confirmatory Phase 3 RACER53 trial. This study was initiated in October 2019 and is currently enrolling. The purpose of this Phase 3 trial is to confirm the clinical findings that were submitted under the Accelerated Approval pathway.
About Duchenne Muscular Dystrophy (DMD)
DMD is a progressive form of muscular dystrophy that occurs primarily in males. DMD causes progressive weakness and loss of skeletal, cardiac, and pulmonary muscles. 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 the use of a wheelchair. Cardiac and respiratory muscle problems begin in the teenage years and lead to serious, life-threatening complications.
Viltolarsen has been granted Rare Pediatric Disease, Orphan Drug and Fast Track Designations in the U.S. The viltolarsen New Drug Application was granted Priority Review by the FDA with an anticipated action date in the third quarter of 2020. In March 2020, viltolarsen was approved in Japan for the treatment of patients with DMD who are amenable to exon 53 skipping therapy. Prior to its approval in Japan, viltolarsen was granted with the SAKIGAKE designation, Orphan drug designation, and designation of Conditional Early Approval System.
About NS Pharma, Inc.
NS Pharma, Inc., is a wholly owned subsidiary of Nippon Shinyaku Co., Ltd. For more information, please visit http://www.nspharma.com. NS Pharma is a registered trademark of the Nippon Shinyaku group of companies.
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SOURCE NS Pharma
October 17th, 2019
Vamorolone Designated Promising Innovative Medicine (PIM) for treatment in Duchenne muscular dystrophy
Rockville, MD –
In the UK the Early Access to Medicines Scheme (EAMS) is a regulatory path by the MRHA that aims to give patients with life threatening or seriously debilitating conditions access to medicines that do not yet have a marketing authorization when there is a clear unmet medical need. The initial step in this process is Promising Innovative Medicine (PIM) designation.
Co-founders of Duchenne UK Alex Johnson and Emily Crossley said, “We are delighted that MHRA has given PIM status to Vamorolone as a treatment for Duchenne Muscular Dystrophy. A PIM designation is the first step of a process that could allow patients earlier access to a new medicine. This is part of the Early Access to Medicines Scheme which Duchenne UK and Joining Jack lobbied for in 2014. We are pleased to see that the scheme may be used for Vamorolone.”
Vamorolone is a first-in-class drug that targets multiple biochemical pathways in DMD patient muscle simultaneously, and in initial open label studies has shown improvements of patient muscle function. A pivotal trial that may lead to drug approval is currently enrolling patients age 4 to 7 years at 6 sites in the United Kingdom (Newcastle University, Royal Hospital for Children [Glasgow], Alder Hey Children’s Hospital [Liverpool], Leeds Teaching Hospital Trust, Great Ormond Street Institute of Child Health [London] and University Hospitals Birmingham). Information on the currently recruiting vamorolone clinical trial with contact information for UK recruitment sites can be found at clinicaltrials.gov.
About the UK Early Access to Medicines Scheme (EAMS)
The UK’s industry-sponsored EAMS aims to give patients with life threatening or seriously debilitating conditions access to medicines that do not yet have a marketing authorization when there is a clear unmet medical need. The EAMS is a two-step process:
Step I is the Designation as a Promising Innovation Medicine (PIM). The PIM designation is an early indication that a medicinal product is a promising candidate for EAMS and gives reassurance that its clinical development is on track by having an early review of its data by the medicines regulator.
Step II is the Scientific Opinion by the Medicines and Healthcare products Regulatory Agency (MHRA, UK regulatory agency). The Scientific Opinion describes the benefits and risks of the medicine and supports the prescriber and patient to make a decision on using the medicine before its license is approved.