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Positive data with vamorolone in DMD

Santhera Announces Presentation by ReveraGen of Positive 18-Month Data with Vamorolone in Duchenne Muscular Dystrophy

 

La Force is happy to share this press release provided by Santhera Pharmaceuticals, October 7, 2019, > PRESS RELEASE <

 

Santhera Pharmaceuticals announces the presentation of data showing continued improvement of muscle function and improved tolerability compared with corticosteroids of 18-month vamorolone treatment in Duchenne muscular dystrophy (DMD). These top-line data were presented on October 5 by Eric Hoffman, Ph.D., CEO of ReveraGen at the World Muscle Society (WMS) congress.

In a late-breaking presentation at the WMS international conference in Copenhagen, Denmark, ReveraGen presented motor function and tolerability data from 23 DMD patients treated with 2.0 or 6.0 mg/kg/day with vamorolone for at least 18 months in the ongoing VBP15-LTE study.

 

Eric Hoffman, Ph.D., Chief Executive Officer of ReveraGen – “These data demonstrate that vamorolone treatment results in persistently improved motor function in DMD patients, similar to that of corticosteroids. Importantly, however, vamorolone treatment over a period of 18 months showed better tolerability with less corticosteroid-specific side effects, including no stunting of the growth of DMD children.”

 

Vamorolone is a first-in-class steroidal anti-inflammatory investigational drug in development as a treatment for DMD to substitute standard corticosteroids (prednisone, deflazacort). This trial is an extension study of the VBP15-003 trial in which 48 DMD patients treated for 6 months over a broad dose range (0.25 to 6.0 mg/kg/day) showed dose-related improvements in multiple gross motor outcomes. Upon exiting this 6-month trial, patients and their physicians preferred to continue vamorolone treatment. 45 boys transitioned to the 2-year long-term extension study VBP15-LTE and all doses were increased to 2.0 or 6.0 mg/kg/day of vamorolone.

At the WMS conference, Dr. Hoffman presented data from 23 patients treated with 2.0 or 6.0 mg/kg/day vamorolone for at least 18 months. Vamorolone treatment consistently and significantly improved standardized motor function outcomes measured as velocity to stand from supine, to run/walk 10 meters and to climb 4 stairs from baseline to month 18. Motor function outcomes for vamorolone treated patients also were consistently better than outcomes for age-matched, steroid naïve patients from an external natural history study (velocity to stand from supine: p=0.085; run/walk 10 meters: p=0.005; climb 4 stairs: p=0.036; all in favour of vamorolone treatment).

Vamorolone compared to standard corticosteroids

Motor function outcomes of vamorolone-treated DMD boys were compared to age-matched prednisone-treated patients from an external control group. Both vamorolone and prednisone treated groups showed similar improvements in these gross motor outcomes, demonstrating that vamorolone exerts therapeutic efficacy similar to standard corticosteroids. Importantly, vamorolone-treated boys showed normal growth rates, and less physician-reported weight gain and Cushingoid features compared to published studies of prednisone and deflazacort. These findings confirm earlier data that indicate a better tolerability profile of vamorolone compared to standard corticosteroids.

Together with previously reported molecular and clinical data, the new 18-month data suggest that dissociative steroidal drug vamorolone maintains efficacy and decreases adverse effects typically reported for corticosteroids in the treatment of DMD. Vamorolone has been granted Orphan Drug status in the US and Europe and has received Fast Track and Rare Pediatric Disease designations by the US FDA.

About Vamorolone – first-in-class dissociative steroid

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

The currently ongoing 48-week Phase IIb VISION-DMD study is designed as a pivotal trial to demonstrate efficacy and safety of vamorolone compared with prednisone and placebo in 120 boys aged 4 to <7 with DMD that have not yet been treated with corticosteroids. Vamorolone is being developed by US-based ReveraGen BioPharma Inc. with participation in funding and design of studies by several international non-profit foundations, the US National Institutes of Health, the US Department of Defense and the European Commission’s Horizon 2020 program. In November 2018, Santhera acquired from Idorsia the option to an exclusive sub-license to vamorolone in all indications and all countries worldwide (except Japan and South Korea).

Clinical trial in Canada

About Santhera

Santhera Pharmaceuticals is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative medicines for rare neuromuscular and pulmonary diseases with a high unmet medical need. Santhera is building a Duchenne muscular dystrophy (DMD) product portfolio to treat patients irrespective of causative mutations, disease stage or age. A marketing authorization application for Puldysa® (idebenone) is currently under review by the European Medicines Agency. Santhera has an option to license vamorolone, a first-in-class dissociative steroid currently investigated in a pivotal study in patients with DMD to replace standard corticosteroids. Santhera out-licensed ex-North American rights to its first approved product, For further information, please visit www.santhera.com. Raxone® and Puldysa® are trademarks 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, and Duchenne Research Fund. ReveraGen has also received generous support from the US Department of Defense CDMRP, National Institutes of Health (NCATS, NINDS, NIAMS), and European Commission (Horizons 2020).

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PolarisDMD Trial in DMD has exceeded target enrollment

Phase 3, PolarisDMD trial of edasalonexent in DMD has exceeded target enrollment

 

La Force is happy to share the latest edition of the Catabasis Connection newsletter

 

Catabasis Pharmaceuticals, Inc. announced today the completion of enrollment for the Phase 3 PolarisDMD trial of edasalonexent in Duchenne muscular dystrophy (DMD). The target enrollment of 125 boys was exceeded due to strong interest from their 40 clinical sites in 8 countries and the support of patient advocacy organizations. Top-line results from the Phase 3 PolarisDMD trial are expected in the fourth quarter of 2020 and the trial is anticipated to support a New Drug Application (NDA) filing in 2021.

PRESS RELEASE

 

Joanne Donovan, M.D., Ph.D., Chief Medical Officer of Catabasis “We are thrilled to reach this important milestone. The interest and feedback from families and trial sites has been overwhelmingly positive. At a time when there are multiple trials for Duchenne, we are very pleased that physicians and families chose the Phase 3 PolarisDMD trial for edasalonexent. Edasalonexent has the potential to be a foundational therapy, providing benefit to boys, regardless of their underlying mutation, with the potential to benefit muscle function, as well as cardiac function and bone health. We look forward to completing the trial next year and are working diligently toward the goal of making edasalonexent available to patients.”

 

The PolarisDMD trial enrolled 130 boys ages 4 to 7 with any mutation type and who had not been on steroids for the past 6 months. The trial is a randomized, double-blind, placebo-controlled trial with 2 to 1 randomization such that two boys receive edasalonexent for each boy that receives a placebo. At the completion of 52 weeks, all boys and their eligible siblings are expected to have the option to enroll in GalaxyDMD, an open-label extension study designed to assess the long-term safety of edasalonexent. Boys can begin or continue treatment with an approved exon skipping therapy in the GalaxyDMD trial, which has a streamlined schedule with visits to trial sites every six months. Read more about these studies here.

 

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 Phase 3 PolarisDMD Trial

The global Phase 3 PolarisDMD trial is a one-year, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of edasalonexent in patients with DMD. The trial enrolled patients ages 4 to 7 regardless of mutation type who had not been on steroids for at least 6 months. Boys on a stable dose of eteplirsen were also eligible to enroll. The primary efficacy endpoint is change in the North Star Ambulatory Assessment score after 12 months of treatment with edasalonexent compared to placebo. Key secondary endpoints include the age-appropriate timed function tests: time to stand, 4-stair climb and 10-meter walk/run. Assessments of growth, cardiac and bone health are also included as important potential areas of differentiation. For each boy that receives a placebo, two boys are receiving 100 mg/kg/day of edasalonexent and after 12 months, all boys are expected to receive edasalonexent in the open-label extension study GalaxyDMD. The PolarisDMD trial design was informed by discussions with regulators as well as input from treating physicians, patient organizations and families of boys affected by Duchenne. Top-line results from the Phase 3 PolarisDMD trial are expected in the fourth quarter of 2020. More information about the Phase 3 PolarisDMD clinical trial is available on clinicaltrials.gov.

 

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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Sarepta Therapeutics receives Complete Response Letter for golodirsen

Sarepta Therapeutics receives Complete Response Letter from the US Food and Drug Administration for golodirsen New Drug Application

Sarepta Therapeutics, Inc announced it had received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding the New Drug Application (NDA) seeking accelerated approval of golodirsen injection for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation amenable to exon 53 skipping. – News Release

 

What is an FDA Complete Response Letter CRL?

Receiving one of these letters means that the FDA has completed its review of a new drug application and decided not to approve it in its present form.

The U.S. Food and Drug Administration (FDA) sends a complete response letter to communicate it has completed its review of a new or generic drug application, and it decided that it will not approve it for marketing in its present form. Receiving one of these letters from the FDA is never good news, but their long-term impact varies. – The Motley Fool

The CRL cites two concerns:

  • The risk of infections related to intravenous infusion ports
  • Renal toxicity with golodirsen was observed in pre-clinical models at doses that were ten-fold higher than the dose used in clinical studies.

Renal toxicity was not observed in Study 4053-101, on which the application for golodirsen was based.

 

Doug Ingram, president and chief executive officer, Sarepta – “We are very surprised to have received the complete response letter this afternoon. Over the entire course of its review, the Agency did not raise any issues suggesting the non-approvability of golodirsen, including the issues that formed the basis of the complete response letter.”

 

Doug Ingram, president and chief executive officer, Sarepta – “We will work with the Division to address the issues raised in the letter and, to the fullest extent possible, find an expeditious pathway forward for the approval of golodirsen. We know that the patient community is waiting.”

 

What is the next step?

Sarepta will immediately request a meeting with the FDA to determine next steps. The ESSENCE study (4045-301), a global, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of golodirsen and casimersen, our exon-45 skipping agent, is ongoing.

More about golodirsen

Like Exondys 51, golodirsen, which Sarepta hopes to sell under the name Vyondys 53, is designed to treat a group of Duchenne patients with a particular type of mutation. Exondys 51 works for about 13% of DMD patients—those whose disease is amenable to exon 51 skipping. If approved, golodirsen would offer treatment to patients with a mutation in exon 53—about 8% of the DMD population.

More interesting links

Sources

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All PolarisDMD sites are now launched

Catabasis announces that all 40 sites, across eight countries, are now fully launched for the Phase 3 PolarisDMD trial of edasalonexent in Duchenne muscular dystrophy!

La Force is happy to share the latest edition of the Catabasis Connection newsletter about the Phase 3 PolarisDMD trial for edasalonexent in Duchenne. The Phase 3 PolarisDMD trial is enrolling boys affected by Duchenne ages 4 to 7, any mutation type, that are not on steroids. This newsletter includes an illustration of the PolarisDMD and GalaxyDMD patient experience.

Clinical trial sites are enrolling rapidly. There is limited space in the United States, Canada and Australia. Locations in the UK, Germany, Ireland, Sweden, and Israel are at capacity. Catabasis anticipates that the final patient screening visits will be completed this September. If you have any questions about the trial > DMDtrials@catabasis.com

Link to the PDF file > https://www.catabasis.com/Catabasis%20Connection%20No.20.pdf

About edasalonexent

Edasalonexent inhibits NF-kB, a protein that plays a fundamental role in skeletal and cardiac muscle disease in Duchenne. By inhibiting NF-kB, edasalonexent has the potential to decrease inflammation and fibrosis, promote muscle regeneration, and slow disease progression. Edasalonexent is being developed as a potential stand-alone therapy and also have the potential to be combined with dystrophin-targeted therapies.

Learn more about edasalonexent

  • Watch this video recorded in November 2016, Dr. Joanne Donovan answers our questions about edasalonexent (CAT-1004)

About Canadian sitesClinical trials in Canada –  PHASE 3 POLARISDMD TRIAL OF EDASALONEXENT IS NOW OPEN FOR ENROLLMENT IN CANADA

About Catabasis

Their mission is to bring hope and life-changing therapies to patients and their families. Their lead program is edasalonexent, an NF-kB inhibitor in development for the treatment of Duchenne muscular dystrophy. Their global Phase 3 PolarisDMD trial is currently enrolling boys affected by Duchenne. For more information on edasalonexent and the Phase 3 PolarisDMD trial, please visit www.catabasis.com or www.twitter.com/catabasispharma.

Stay in touch with Catabasis

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

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PTC Provides Update on Translarna™

PTC Provides Update on Translarna™ (ataluren) Application for Label Expansion

June 28, 2019 > Original press release <

PTC Therapeutics, Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has completed their review of a proposed indication extension of Translarna™ (ataluren) for the treatment of patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) who are non-ambulatory. While the CHMP adopted a negative opinion of the extension, PTC was informed by EMA representatives that the European Public Assessment Report (EPAR) would be updated to clarify that patients who start Translarna while ambulatory are not required to discontinue treatment after the loss of ambulation.

 

Translarna is currently indicated for ambulatory Duchenne patients who are over two years of age; the requested extension would have allowed for the inclusion of non-ambulatory patients in the label. PTC plans to seek a re-examination of the procedure within the next two weeks and expects the new examination to last approximately four months. 

 

Marcio Souza, Chief Operating Officer, PTC Therapeutics, Inc – “While we are disappointed with the current outcome of the label expansion procedure and its impact on non-ambulatory patients with nonsense mutation Duchenne Muscular Dystrophy, we are pleased that patients on Translarna can remain on treatment after the loss of ambulation. We remain committed to work with the CHMP to clarify the open questions and are confident we will be able to demonstrate the pulmonary benefit of Translarna in non-ambulatory patients.”

 

The clinical data supporting the extension is based on results supporting the positive impact in the Force Vital Capacity (FVC) parameters for patients treated with Translarna in study 019, a long-term, open-label study, and study 025 (STRIDE Registry) when compared to matched natural history controls. This is in addition to currently approved labelling stating that the pharmacokinetics (PK) and safety profiles are comparable between ambulatory and non-ambulatory nmDMD patients and that no dose adjustment is necessary when patients become non-ambulatory. The CHMP opined that the comparable PK might not ensure efficacy in non-ambulatory patients since muscle mass is reduced in this patient group. PTC and members of the scientific community expressed disagreement with this understanding during the oral explanation.

Translarna received the annual renewal of its conditional marketing authorization in June 2019 for nonsense mutation Duchenne muscular dystrophy patients who are ambulatory and two years and over. In addition, in connection with the June 2019 renewal, PTC’s specific obligation for the submission of the results of Study 041, an ongoing clinical trial of ataluren, has been extended to September 2022.

 

Translarna™ (ataluren) in Canada

Translarna™ (ataluren) has not received marketing authorization in Canada. This treatment must, first and foremost, be evaluated and approved for the Canadian market by Health Canada. To approve a drug, Health Canada must ensure that it meets certain safety, efficiency and quality requirements.

La Force Foundation hopes that Translarna™(ataluren) will be marketed in Canada as soon as possible so that all young patients can benefit.

More about Translarna (ataluren)

Pioneer in the DMD therapy > Watch the Vlog

PolarisDMD Welcomes European Sites!

27 global sites currently open for enrollment

Clinical trial sites in Europe are now open for enrollment in Bristol and Manchester, England; Munich and Hamburg, Germany; Dublin, Ireland; and Gothenburg, Sweden, with additional sites in Europe expected in the coming weeks.

This means that PolarisDMD is now active in 7 countries! The Phase 3 PolarisDMD clinical trial of edasalonexent in Duchenne is enrolling boys ages 4 to 7 (up to 8th birthday), regardless of mutation type, who have not been on steroids for the past six months.

 

GalaxyDMD, MoveDMD, PolarisDMD?

GalaxyDMD is a recently-launched, open-label extension study. It is designed to collect long-term data in boys taking edasalonexent as they get older and to provide the opportunity to stay on the drug while edasalonexent is in clinical development. All boys in Phase 2 MoveDMD trial will transition to GalaxyDMD once they complete their final visit in MoveDMD, which can often be performed at the same visit. When boys in Phase 3 PolarisDMD trial complete the 12-month trial, they will also have the opportunity to transition to GalaxyDMD. For greater convenience, now that additional sites are open for the Phase 3 PolarisDMD study, there is flexibility for boys who participated in Phase 2 MoveDMD trial to relocate to a site closer to home, if desired. And Catabasis is especially pleased to share that once boys from MoveDMD and PolarisDMD enter GalaxyDMD, their brothers’ ages 4 to 10 (up to 11th birthday) who meet the inclusion criteria are also able to participate in GalaxyDMD and receive edasalonexent! Site visits for GalaxyDMD are once every six months.

EDASALONEXENT: THE POTENTIAL TO PRESERVE MUSCLE FUNCTION IN BOYS WITH DUCHENNE

The primary outcome measurement in Phase 3 PolarisDMD trial (also called the “endpoint”) is the North Star Ambulatory Assessment (NSAA), which was designed to assess muscle function in ambulatory boys affected by Duchenne. The NSAA consists of 17 different measures similar to activities in daily life, such as standing on one leg or rising from a chair.

About Edasalonexent (CAT-1004)

Edasalonexent (CAT-1004) is an investigational oral small molecule that is being developed as a potential therapy for all patients affected by DMD, regardless of their underlying mutation. Edasalonexent inhibits NF-kB, which is a key link between loss of dystrophin and disease progression in DMD. NF-kB has a fundamental role in skeletal and cardiac muscle disease in DMD. We are currently enrolling our global Phase 3 PolarisDMD trial to evaluate the efficacy and safety of edasalonexent for registration purposes. 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. Edasalonexent continues to be dosed in the open-label extension of the MoveDMD trial. The FDA has granted “orphan drug,” fast track, and rare pediatric disease designations and the European Commission has given orphan medicinal product designation to edasalonexent for the treatment of DMD. For a summary of clinical results, please visit www.catabasis.com.

Watch this video recorded in November 2016, Dr. Joanne Donovan answers our questions about edasalonexent (CAT-1004)

Learn more about PolarisDMD clinical trial

About Catabasis

Their mission is to bring hope and life-changing therapies to patients and their families. Their lead program is edasalonexent, an NF-kB inhibitor in development for the treatment of Duchenne muscular dystrophy. Their global Phase 3 PolarisDMD trial is currently enrolling boys affected by Duchenne. For more information on edasalonexent and the Phase 3 PolarisDMD trial, please visit www.catabasis.com or www.twitter.com/catabasispharma.

Join Catabasis mailing list > http://www.catabasis.com/patients-families/for-further-information.php

 

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

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FibroGen receives orphan drug designation for Pamrevlumab

FibroGen Receives Orphan Drug Designation from the U.S. FDA For Pamrevlumab for the Treatment of Duchenne Muscular Dystrophy

 

FibroGen, Inc. a leading biopharmaceutical company discovering and developing a pipeline of first-in-class therapeutics, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for the company’s anti-CTGF antibody, pamrevlumab, for the treatment of patients with Duchenne muscular dystrophy (DMD).

DMD is caused by the absence of the dystrophin protein, resulting in abnormal muscle structure and function and buildup of fibrosis in muscle, which diminishes mobility, pulmonary function, and cardiac function. Constant myofiber breakdown results in persistent activation of myofibroblasts and aberrant production of extracellular matrix (ECM) proteins, including collagens and fibronectin, leading to extensive fibrosis in skeletal muscles.

Pamrevlumab is a fully human monoclonal antibody that inhibits the activity of connective tissue growth factor, or CTGF, a critical mediator in the progression of fibrosis and related serious diseases.

 

Elias Kouchakji, M.D., Senior Vice President, Clinical Development and Drug Safety – “We are pleased to have received Orphan Drug Designation from the FDA for pamrevlumab in the treatment of DMD. There is a high unmet medical need for patients suffering from this debilitating disease needing a new treatment option. All 21 non-ambulatory DMD patients in our ongoing phase 2 study with pamrevlumab have completed the first 52 weeks of treatment. We are evaluating a number of clinical parameters in this study, including lung function, cardiac function, and upper extremity muscle function, and tissue fibrosis. We look forward to the continued development of this investigational therapeutic.” News release here.

 

About Pamrevlumab

Pamrevlumab is a first-in-class antibody developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. Pamrevlumab is advancing towards Phase 3 clinical development for the treatment of idiopathic pulmonary fibrosis (IPF) and pancreatic cancer. Pamrevlumab has been granted Orphan Drug Designation in IPF, pancreatic cancer, and Duchenne muscular dystrophy (DMD). Pamrevlumab has also received Fast Track designation from the U.S. Food and Drug Administration for the treatment of patients with IPF and patients with locally advanced unresectable pancreatic cancer and is currently in a Phase 2 trial for DMD. Across all trials, pamrevlumab has consistently demonstrated excellent safety and tolerability profile to date. For information about pamrevlumab studies currently recruiting patients, please visit www.clinicaltrials.gov.

Pamrevlumab is being evaluated in ongoing Phase 2 clinical studies for the treatment of idiopathic pulmonary fibrosis, pancreatic cancer, and Duchenne muscular dystrophy.

About Orphan Drug Designation

Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug. This designation qualifies the sponsor for various development incentives of the Orphan Drug Act, including tax credits for qualified clinical testing, to advance the evaluation and development of products that demonstrate promise for the diagnosis and treatment of rare diseases or conditions. Orphan Drug Designation can also convey up to seven years of marketing exclusivity if the compound receives regulatory approval from the FDA.

Health Canada has quietly deleted from its website all references to a planned framework for rare-disease drugs that dates back to 2012 and was intended to improve the availability of such drugs in Canada.

Canada is one of the only developed countries without a regulatory framework for rare-disease drugs, also known as orphan drugs.

 

About FibroGen

FibroGen, Inc., headquartered in San Francisco, California, with subsidiary offices in Beijing and Shanghai, People’s Republic of China, is a leading biopharmaceutical company discovering and developing a pipeline of first-in-class therapeutics. For more information, please visit www.fibrogen.com.

Deepen a few words

CTGF, also known as CCN2 or connective tissue growth factor

CTGF has essential roles in many biological processes, including cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair and is critically involved in fibrotic disease and several forms of cancers. A tissue is defined as the substance made up of cells of the same composition that all perform the same function. Connective tissue primarily serves to support and protect the other types of body tissues. They are located between the organs and constitute a considerable part of the body’s cellular tissue. They are primarily composed of cells, notably fibroblast cells that create another significant component of the body: collagen fibres, which ensure the resistant quality of connective tissue. This tissue also contains a substance called the extracellular matrix in which the cells rest.

Myofibroblasts

Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process primarily supported by (myo)fibroblasts.

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Phase 3 PolarisDMD trial of edasalonexent is now open for enrollment in Canada

Catabasis is enrolling boys ages 4 to 7 (up to 8th birthday), any mutation type, who have not been on steroids for at least the past six months.

 

What is Edasalonexent?

Edasalonexent (CAT-1004 is being developed as a potential foundational disease-modifying therapy for all patients affected by DMD, regardless of their underlying mutation. It is an investigational oral small molecule. Edasalonexent inhibits NF-kB, a protein that is activated by DMD and drives inflammation and fibrosis, muscle degeneration and suppresses muscle regeneration. By inhibiting NF-kB, edasalonexent has the potential to decrease inflammation and fibrosis, promote muscle regeneration, and slow disease progression. Edasalonexent was designed as a stand-alone therapy and may also enhance the efficacy of dystrophin targeted therapies.

 

Potential bone health benefits of edasalonexent

Why is bone health so important in Duchenne?

Boys with Duchenne are at an increased risk of bone fractures and should be monitored yearly to check for fractures. Early detection is critical. Strong bones are essential to help boys grow taller! Some therapies used to treat Duchenne have an additional negative impact on bone health and can increase the frequency of long bone and spine fractures.

Catabasis believes that edasalonexent has the potential to benefit bone health, which is why they are studying it in their Phase 3 PolarisDMD trial. Because edasalonexent is an NF-kB inhibitor, it has the potential to reduce inflammation and promote muscle regeneration, and that can strengthen bones. Catabasis will perform x-rays and body scans at the beginning and end of the study to check on bone health!

 

PolarisDMD in Canada

If you’d like to learn more, contact Catabasis at DMDtrials@catabasis.com. Catabasis is also sharing updates on edasalonexent @CatabasisPharma on Facebook, Twitter and Instagram if you are interested in the latest updates. Get the story behind the PolarisDMD experience! – Here

Ontario

  • Children’s Hospital-London Health Sciences Centre, this site is expected to be enrolling soon
    • Principal Investigator: Craig Campbell
  • Children’s Hospital Eastern Ontario, this site is expected to be enrolling soon
    • Principal Investigator: Hugh McMillian

Alberta

  • Alberta Children’s Hospital is actively recruiting
    • Principal Investigator: Jean Mah

Quebec

  • Sainte-Justine Hospital, this site is expected to be enrolling soon
    • Principal Investigator: Cam-Tu Nguyen

 

Sources and for more information

More about Catabasis: www.catabasis.com

Portrait of Duchenne – edasalonexent cat-1004 – La Force DMD

Blog post La Force

More information about the Polaris DMD trial: Catabasis – Polaris DMD

Phase III Study of Edasalonexent in Boys With Duchenne Muscular Dystrophy (PolarisDMD)

 

 

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Sarepta Therapeutics announces positive results from the ESSENCE study

Sarepta Therapeutics, Inc., a leader in precision genetic medicine for rare diseases, announced positive results from its interim analysis of muscle biopsy endpoints comparing casimersen treatment to placebo in the ESSENCE study.

ESSENCE is a global, randomized double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of casimersen and golodirsen in patients amenable to skipping exons 45 or 53, respectively.

After soliciting feedback from the FDA, Sarepta conducted an interim analysis for levels of dystrophin protein expression in those patients who are amenable to exon 45 skipping to determine the potential for a New Drug Application (NDA) filing based on dystrophin as a surrogate endpoint. With these results, the Company intends to work toward submission of an NDA for casimersen in the middle of 2019. News release

 

“We are pleased to see that the anticipated exon skipping after treatment resulted in a statistically significant mean increase of dystrophin protein, as measured by western blot*.” -Professor Francesco Muntoni, University College London

“This is the third exon-skipping agent to have shown a statistically significant increase in dystrophin production, and reinforces our confidence in the exon-skipping approach for treating Duchenne patients with amenable mutations.” -Professor Francesco Muntoni, University College London

“The casimersen results and submission of our application for golodirsen earlier this year further validate our RNA* research engine. If golodirsen and casimersen are approved, nearly a third of the boys and young men living with DMD in the United States could benefit from our RNA therapies. We continue to advance toward our ultimate goal of profoundly improving the lives of as many patients around the world with DMD as possible.” -Doug Ingram, Sarepta Therapeutics’ president and chief executive officer

ESSENCE study

ESSENCE is a global Phase 3 study evaluating the efficacy and safety of casimersen and golodirsen in patients amenable to skipping exons 45 or 53, respectively. Golodirsen and casimersen rely on the same approach than Exondys 51.

Positive results

The interim analysis found a statistically significant increase in dystrophin production in casimersen-treated participants compared to baseline and placebo. Golodirsen and casimersen rely on the same approach than Exondys 51.

Submitting to the FDA

Based on positive results, the company intends to schedule a pre-NDA (New Drug Submission) meeting with FDA (Food and Drug Administration) US and plans to submit an NDA for casimersen in the middle of 2019.

Key findings from the interim analysis include:

  • Dystrophin protein increased to 1.736%. By comparison, treatment with Exondys 51 was shown to result in dystrophin levels of 0.93% of normal after 180 weeks.
  • A statistically significant difference in the mean change from baseline to week 48 in dystrophin protein was observed between the casimersen-treated arm compared to the placebo arm.
  • A statistically significant positive correlation between exon 45 skipping and dystrophin production was observed.
  • The study is ongoing and remains blinded to collect additional efficacy and safety data.

Sarepta exon skipping therapy

  • Exondys 51 > skipping exon 51 = 13% DMD patients
  • Golodirsen > skipping exon 53 = 8% DMD patients
  • Casimersen > skipping exon 45 = 8% DMD patients

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.

Duchenne muscular dystrophy (DMD) is caused by a lack of dystrophin

Dystrophin is a protein found in muscle cells that, while present in minimal amounts, 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 critical structural role in muscle fiber function. Progressive muscle weakness in the lower limb’s 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.

RNA-targeted therapeutics are powerful tools

Humans have about 22,000 genes, which contain the blueprints for producing proteins that perform essential functions in the body.

Proteins are molecular workhorses involved in almost every function in our bodies, and defective proteins often result in disease. More specifically, some diseases may be caused by the over-production of one or more proteins, while other diseases are caused by protein deficiencies.

Proteins are produced in cells, where genes in the DNA are “transcribed” into RNA templates, which are then processed and “translated” into proteins by  the cellular machinery.

RNA-targeted therapeutics direct the cellular machinery involved in making proteins. These drugs can be designed to increase or decrease the production of a protein involved in a disease.

By working at the genetic level, RNA-targeted therapeutics are powerful tools with the potential to address diseases that otherwise could not be treated with traditional small molecule or biologic drugs.

Watch Sarepta video here

What is Exon Skipping

Mutations in the dystrophin gene are one cause of DMD. Most commonly, one or more exons (a portion of a gene) are missing, and the remaining exons don’t fit together correctly. (Think of a zipper that doesn’t work correctly, because teeth are missing.)

Because of this error, cells cannot make the dystrophin protein that muscles need to work properly. Without it, muscle cells become damaged and, over time, are replaced with scar tissue and fat.

To fix the broken genetic machinery, scientists are developing drugs that skip over parts that contain missing or defective exons. In this way, the machine can produce a less defective dystrophin protein, which may improve muscle function in children with exon mutations.

Sarepta investigational therapies in the ESSENCE study use a technique referred to as exon skipping. Skipping a specific exon next to the mutation is intended to allow the body to make a shortened form of the dystrophin protein.

Sources

Sarepta Therapeutics, Inc.

Clinical Trials

Biopharma Dive

Cure Duchenne

Golodirsen

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Idebenone for Duchenne muscular dystrophy

February 25, 2019

Santhera Pharmaceuticals announces results from the SYROS study.

 

The primary objective of this study was to evaluate the long-term evolution of the respiratory function in patients who maintained treatment with idebenone for up to 6 years compared to their preceding off-idebenone period.

 

Respiratory Function in DMD

In boys and men with DMD, weakness of respiratory muscles leads to a progressive decline in their ability to move air into/out of their lungs, leading to sleep disturbances and respiratory infections, especially when patients have lost their ability to walk. Studies estimate 55-90% of patients with DMD die from pulmonary complications.

Acute respiratory failure can occur due to:

  • Compromised respiratory dysfunction complicated by mucus plugging and further weakening of inspiratory/expiratory muscles
  • Repeated cases of pneumonia, hospitalizations and intubations

Decreased ability to cough leads to retained secretions and high risk of recurrent respiratory tract infections.

 

The result of this study, which is consistent with outcomes from the pivotal DELOS study, demonstrated that:

  • Switching to and maintaining long-term treatment with idebenone reduced the annual rate of decline in the forced vital capacity percent of predicted (FVC%p) by 50%. Forced Vital Capacity is one of the tests of lung function. FVC is a kind of forced expiration. (Which reflects the strength of the respiratory muscles)
  • The treatment effect was consistently maintained year-on-year for up to 6 years.
  • These findings are further supported by consistent reductions in the rate of both inspiratory and expiratory respiratory function loss over the same period.
  • Prolonged treatment with idebenone also reduced the risk of important patient-relevant outcomes, including bronchopulmonary adverse events and hospitalizations due to respiratory causes.

 

“We are very excited to see that the significant treatment effect with idebenone observed in our 52- week Phase III DELOS study is maintained over the long-term. The new findings are highly relevant for DMD patients in respiratory decline who have an urgent need for a therapy to modify the declining course of respiratory function decline and ultimately delay the need for assisted ventilation.” -Kristina Sjöblom Nygren, MD, Chief Medical Officer and Head of Development at Santhera.

 

About idebenone

Idebenone is a synthetic molecular formula similar to coenzyme Q10. Chemically, it is an organic compound of the family of quinones that can slow the loss of respiratory function.

Mitochondria are specialized structures in the human body that serve as batteries, powering various functions of the cell and the organism as a whole.

Mitochondria produce the energy necessary for the cell functioning through a process called “cellular respiration” which requires oxygen and provides energy. During cellular respiration, some toxic forms of oxygen (called oxygen free radicals) can be produced. These free radicals must be neutralized by other substances to avoid cellular damage.

Idebenone is expected to act as a neutralizer of these toxic forms of oxygen. Thus, idebenone is expected to have an antioxidant effect, and consequently prevent cellular damage.

Idebenone is optimized to dissolve in water and lipids and able to cross the mitochondrial membrane.

Idebenone is a medicine that is under investigation for the treatment of DMD. It has not yet been approved by the U.S. FDA, and the safety and efficacy continue to be evaluated in clinical trials.

 

Status

Santhera’s Raxone® (idebenone) is authorized in the European Union, Norway, Iceland, Liechtenstein, Israel and Serbia for the treatment of Leber’s hereditary optic neuropathy (LHON) and is currently commercialized in more than 20 countries. For further information, please visit www.santhera.com. Raxone® is a trademark of Santhera Pharmaceuticals.

Santhera has been granted orphan drug designation for Raxone for the treatment of DMD in Europe and the US. The US Food and Drug Administration (FDA) has also granted rare pediatric disease designation and Fast Track designation for idebenone for the treatment of DMD. Furthermore, the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) designated idebenone as Promising Innovative Medicine (PIM) and as a suitable candidate for entry into Step II of the EAMS process.

 

About Santhera Pharmaceuticals

Santhera is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative medicines for rare and other diseases with high unmet medical needs. They are focusing on the development of treatments for neuro-ophthalmological, neuromuscular and pulmonary diseases that currently lack treatment options, such as Leber’s hereditary optic neuropathy (LHON), Duchenne muscular dystrophy (DMD), congenital muscular dystrophy (CMD) and cystic fibrosis (CF).

 

Sources

Santhera’s SYROS Study Shows Long-term Efficacy with Idebenone in Slowing Respiratory Function Loss in Patients with Duchenne Muscular Dystrophy

www.siderosdmd.com

Raxone-guides-spring-2019

www.takeabreathdmd.com

www.breatheduchenne.com