Phrixus Pharmaceuticals announces European Access Program for Carmeseal- MDTM (P-188 NF) for patients with Duchenne muscular dystrophy

by Admin 12/1/2014 5:39:00 PM
Phrixus Pharmaceuticals announces European Access Program for Carmeseal- MDTM (P-188 NF) for patients with Duchenne muscular dystrophy
- Ethicor to distribute Carmeseal-MDTM (P-188 NF) in Europe for the treatment of respiratory and cardiac dysfunction in Duchenne muscular dystrophy (DMD) -
ANN ARBOR, MI – 2 December 2014 – Phrixus Pharmaceuticals, Inc. and Ethicor Pharma Ltd. today announced the initiation of their European Access Program (EAP) for Carmeseal-MDTM (P-188 NF). EAP is intended to make Carmeseal-MD available to patients with respiratory and cardiac deficits in DMD through their specialty physicians, primarily cardiologists and pulmonologists, as unlicensed medicinal product (‘Special’). In accordance with local regulations, Ethicor will make Carmeseal-MD available in January 2015 to such patients regardless of their genetic mutation. "For boys and young men with DMD and for their parents time is of the essence. We are committed to making Carmeseal-MD available to patients and their physicians using the most expeditious pathway available,” stated Thomas A. Collet, President and Chief Executive Officer of Phrixus Pharmaceuticals, Inc.
The underlying agreement provides Ethicor with the distribution rights to Carmeseal-MD in the European Union, with the possibility of an expansion to other regions of the world, excluding the United States, Canada and Mexico, prior to and until the registration of the product in the different countries covered by the agreement. Under the European medicines legislation (Directive 2001/83/EC, Article 5(1)), Ethicor will be able to supply, prior to regulatory approval, Carmeseal- MD as a “Special”. A “Special” may be requested by an authorized healthcare professional to meet the special needs of an individual patient under their direct responsibility. Specials cannot be actively promoted to healthcare professionals. Once Carmeseal-MD becomes an approved drug in a given country, the marketing rights to the approved product in that country revert back to Phrixus.
About Carmeseal-MDTM
Carmeseal-MD (Poloxamer 188 NF) has been in clinical development for unrelated indications and has been used as excipient for several decades. In animal models of DMD, it has been shown to improve the efficiency of damaged hearts and to improve
- more -
the performance of damaged diaphragms with once-a-day subcutaneous administration at low doses. When infused into the bloodstream, it encounters and binds to microscopic tears in the muscle. This prevents the pathological leakage of calcium into the cells, which causes calcium overload and keeps the muscle from performing as required. Carmeseal-MD is expected to have its effect in patients with DMD irrespective of the genetic defect that causes the disease.
About Duchenne muscular dystrophy (DMD)
DMD is the most devastating of the muscular dystrophies. It is a genetic disease that affects about 20,000 boys and young men in the United States and a comparable number in Europe. The hallmarks of DMD are skeletal muscle weakness, followed by respiratory distress and heart failure. As a degenerative disease it inevitably leads to premature death, most commonly through respiratory failure but now increasingly through heart failure.
About Phrixus Pharmaceuticals, Inc.
Phrixus Pharmaceuticals, Inc. is developing Carmeseal as Carmeseal-MDTM (P-188 NF for subcutaneous injection) for DMD and as Carmeseal-HFTM (P-188 NF for intravenous administration) for acute decompensated heart failure. Phrixus has assembled the leading global patent portfolio for the use of poloxamers in DMD, heart failure and respiratory dysfunction. For more information: Thomas A. Collet, thomas.collet@phrixuspharmaceuticals.com orwww.phrixuspharmaceuticals.com.

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World Duchenne Awareness Day - 7th of September 2014

by Admin 9/6/2014 11:08:00 AM

 

On the 7th of September 2014, the world will come together for world Duchenne awareness day. The 7th of the 9th has been chosen to represent the 79 exons in the dystrophin gene Dystrophin is the protein missing in boys and girls with Duchenne. Duchenne Charities around the world will raise awareness for boys and young men living with Duchenne muscular dystrophy.This day will be a focal point for the worldwide Duchenne Muscular Dystrophy community with the aim to bring this cruel condition to the attention of a wider global audience. We want to tell you about Duchenne Muscular Dystrophy, how it devastates the lives of the boys who suffer from it and the impact it has on their families and carers. We want to show you why we need to improve the situation for all Duchenne patients who urgently need better access to good care and facilities.

On the 7th of September there will be events and activities all over the world and we have also made a short movie entitled ‘The Many Faces of Duchenne’. This movie which is available on a dedicated website (www.worldduchenneawarenessday.org) highlights the many challenges Duchenne patients are facing. However, in contrast to the physical weakness which Duchenne patients have to cope with, the movie also shows their incredibly strong will to live and take part in life to the greatest extent possible.

Duchenne Muscular Dystrophy affects approximately 250.000 children around the world. The vast majority of Duchenne patients are boys with one in every 3500 newborn boys suffering from Duchenne; only very few girls have this rare disease. Duchenne boys first lose the ability to walk during their childhood days and as they grow into adolescents they also lose the ability to use their arms, carry out everyday activities such as writing or feeding themselves, and their ability to breathe deteriorates as well. As they grow into young men Duchenne boys finally succumb to the disease and die due to respiratory problems or heart failure. But many don't reach adulthood in the first place.

Duchenne patients urgently need good medical care. They need access to specialized centers and multidisciplinary care as well as diagnostics. But we also need to improve the situation concerning the reimbursement of costs for medical care, drugs and/or equipment. Finally, it is absolutely essential that Duchenne boys get improved access to education and increased support to overcome hurdles related to physical and to learning issues. Access to good care and facilities improves not only the quality of life for Duchenne patients but it is also proven to prolong lifespans by between 10 and 20 years. The knowledge about good medical care is widely available, but the majority of Duchenne boys still doesn't have access to good care and facilities. We have to address this and find ways to improve the situation for all Duchenne patients.

There is currently no cure for Duchenne Muscular Dystrophy but for the first time ever there are several drugs under development. In Europe the first drug already received Conditional Approval. Now we have to make sure that all Duchenne patients will benefit from new developments as soon as possible! 

Find out more about the medical care required for those who have Duchenne Muscular Dysptrophy by reading the imperatives of DMD which is now available in 17 different languages. 

 

Dedicated Awareness Website and Video 

We would like to invite you to visit our dedicated World Duchenne Awareness Day website on www.worldduchenneawarenessday.org

 

 

 

Facebook 

Apart from the video you will also find a lot of information on Duchenne Muscular Dystrophy and the activities around the world there. Our Duchenne boys really need your help. The more you know about their plight the more you may be able to support them, directly or indirectly, to improve access to good medical care and facilities. 

You can also like the facebook page here: https://www.facebook.com/worldduchenneawarenessday

Twitter

Please tweet about "World Duchenne Awareness Day" using the hastag #WDAD14 

Duchenne out of this World 

If you would like to show your support, one idea from a Duchenne organisation in Spain is to ‘send a message to the sky’ . At 1pm on Sunday 7th September, send an object into the sky – this could be a balloon, paper aeroplane, sky lantern or a kite – with the message ‘Duchenne out of this world’ written on it. Take a picture and post it with the hashtag #WDAD14.



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PTC Therapeutics Receives Conditional Approval in the European Union for Translarna™ For the Treatment of Nonsense Mutation Duchenne Muscular Dystrophy

by Admin 8/4/2014 11:35:00 AM
August 4, 2014

PTC Therapeutics Receives Conditional Approval in the European Union for Translarna™ For the Treatment of Nonsense Mutation Duchenne Muscular Dystrophy

- The first treatment approved for DMD –

 

SOUTH PLAINFIELD, NJ – August 4, 2014 – PTC Therapeutics, Inc. (NASDAQ: PTCT) today announced that the European Commission has granted conditional marketing authorization for Translarna™ (ataluren), in the European Union (EU) for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD) in ambulatory patients aged five years and older.

"We are delighted that Translarna was approved for the treatment of nonsense mutation Duchenne muscular dystrophy. By targeting the underlying cause of DMD, it has the potential to change the course of the disease. We are moving rapidly to make this product available to patients in the EU as we continue our global efforts to fulfill our vision of making Translarna available to all the boys it may benefit," stated Stuart W. Peltz, Ph.D., CEO of PTC Therapeutics, Inc. "We are grateful to the patients, families, advocacy groups and physicians who have supported PTC Therapeutics through many years of research and development of Translarna. The DMD community has been waiting a long time for treatment options and this conditional approval marks an important day for us all."

The authorization allows PTC to market Translarna in the 28 countries that are Member States of the European Union, as well as European Economic Area members Iceland, Liechtenstein and Norway. As part of the conditional marketing authorization, PTC is obligated to complete its confirmatory Phase 3 trial in nmDMD (ACT DMD) and submit additional efficacy and safety data from the trial.

The approval is based on the safety and efficacy results from a randomized double-blind multicenter study in 174 nmDMD patients for 48 weeks and our additional retrospective analyses of study data. The primary endpoint evaluated the effect of Translarna on ambulation as assessed by the change in distance walked (six-minute walk distance - 6MWD) during a six-minute walk test (6MWT). The post-hoc analysis showed that from baseline to Week 48, patients receiving Translarna (40 mg/kg/day given in 3 doses) had a 12.9 meter mean decline in 6MWD, and patients receiving placebo had a 44.1 meter mean decline in 6MWD. Thus the mean change in observed 6MWD from baseline to Week 48 was 31.3 meters better in the Translarna group than in the placebo group (p=0.056). Furthermore, in more severely affected patients whose baseline 6MWD was less than 350 meters, the mean change in observed 6MWD from baseline to Week 48 was 68 meters better in the Translarna group than in the placebo group. Patients on Translarna also showed a slower rate of decline in ambulation based on an analysis of time to 10 percent worsening in 6MWD. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency found that these results suggest that Translarna slows the loss of walking ability in nmDMD patients.

Additionally, based on a retrospective analysis, patients receiving treatment also trended better in secondary endpoints such as stair climb and stair descend time-function tests, which the CHMP also found to suggest slowing of nmDMD progression relative to placebo. Safety results showed that Translarna was generally well tolerated. Serious adverse events were infrequent, and none was considered to be related to Translarna. The most frequent adverse reactions at the recommended dose were nausea, vomiting, and headache. These adverse reactions generally did not require medical intervention, and no patients discontinued Translarna treatment due to any adverse reaction.

"The world's first approved treatment for the underlying cause of DMD marks a very important moment for patients and their families. It is our highest priority to make Translarna available to patients and we will be working with regulators, payers, physicians and patient organizations to make that a reality." stated Mark Rothera, Chief Commercial Officer, of PTC Therapeutics, Inc.



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Prosensa Announces Regulatory Path Forward for Drisapersen as a Potential Treatment for DMD

by Admin 6/3/2014 6:53:00 AM
June 3, 2014

Plans to Submit a New Drug Application to the FDA this Year; Dialogue with EMA continues with intent to seek approval

 

 

Leiden, The Netherlands, June 3, 2014 (GLOBE NEWSWIRE) -- Prosensa Holding N.V. (NASDAQ: RNA) the Dutch biopharmaceutical company focusing on rare diseases with a high unmet medical need, today announced that the United States Food and Drug Administration (FDA) has outlined a regulatory path forward, under an accelerated approval pathway, for drisapersen, the Company's lead program for the potential treatment of Duchenne Muscular Dystrophy (DMD). In addition, the company has been interacting with the European Medicines Agency (EMA) and based on these interactions intends to file in Europe as well.

Following the positive feedback from the FDA, Prosensa has confirmed that it will pursue a New Drug Application (NDA) filing for drisapersen with theFDA, under an accelerated approval pathway based on existing data. The company plans to submit a file later this year and will commit to the initiation of two confirmatory post-approval studies. "Given the urgent need to find effective therapies for boys afflicted with this devastating disease, we could not be more pleased with this favorable outcome and with the regulatory authorities' willingness to advance investigational products for the treatment of DMD" said Hans Schikan, Chief Executive Officer of Prosensa.

"We have been diligently preparing for multiple scenarios since acquiring the rights back from GSK in January and completing our more detailed analysis of the drisapersen dataset. The progress announced today is remarkable news for boys and their families, and we remain dedicated to enabling long term patient access to drisapersen and our follow-on products as novel treatments for DMD" he said.

The FDA has outlined the following approaches for confirmatory trials, which the Company is urged to initiate both as soon as possible, as quoted from the guidance letter:

1.       "A historically-controlled trial might be acceptable to confirm clinical benefit following accelerated approval. We note that a historically-controlled study is likely to provide interpretable evidence of efficacy only if the beneficial effect of drisapersen is large, by clearly showing that performance is better in drisapersen-treated subjects than could be reasonably expected, based on knowledge of the natural history of the disease. The effect size would have to be sufficient to overcome the uncertainty inherent in historically controlled trials, and motivational factors that can affect the results.

2.       A randomized, placebo-controlled trial of another exon-skipping drug with a similar mechanism of action, directed at a different exon (e.g., PRO044 or PRO045), with demonstration of a correlation between dystrophin protein production and definitive clinical benefit on 6-minute walk or another measure, could provide confirmatory evidence of drisapersen's clinical benefit if approval were based on a surrogate endpoint."

In conjunction with commencing confirmatory post-approval studies of drisapersen, Prosensa will continue with its plans to re-dose an initial cohort of boys in the third quarter of 2014 who have previously participated in clinical studies with drisapersen. Based on the guidance, one option is  to enroll a number of previously treated patients in these confirmatory studies. Moreover, Prosensa's natural history study, which has enrolled 250 patients, can serve as a historical control.

"Improved understanding of the natural history of DMD and developing effective therapies takes the commitment of pioneers such as Prosensa, and we welcome the news that the FDA is committed to accelerating the pathway for approval of drisapersen and potentially for follow-on exon-skipping therapies" said Dr. Nathalie Goemans, Head of the Neuromuscular Reference Center for Children at the University Hospitals Leuven (UHL) in Belgiumand one of the key investigators in various drisapersen studies.

Prosensa has the most comprehensive pipeline of targeted RNA-based products in development for the treatment of DMD, with three other exon skipping therapies in Phase I/II clinical studies and two programs in pre-clinical development, all of which have been granted orphan drug designation in the US and EU.  Dose finding studies for PRO044 have been completed and are ongoing for PRO045 and PRO053.



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United Parent Project Muscular Dystrophy to host webinar on Translarna (Ataluren)

by Admin 5/30/2014 7:39:00 AM

June 3, 2014 at 1:00pm EST (7pm CEST)

 

In a webinar hosted by United Parent Project Muscular Dystrophy, Robert Spiegel, MD, FACP, chief medical officer of PTC Therapeutics, will present an overview of the positive opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency regarding the company’s application for a conditional marketing authorization of TranslarnaTM(ataluren) for the treatment of nonsense mutation Duchenne muscular dystrophy, and what this decision means for families living in and outside the EU.

 

Additional Information:


To Participate:

  1. Visit ReadyTalk.com and use participant code 9449985. (Be sure to test your computer beforehand)
  2. Audio Dial-In Information:
    • U.S. & Canada: Dial 866.740.1260 and use the Access Code 9449985
    • Outside the U.S. and Canada: Lookup your number


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PTC THERAPEUTICS RECEIVES POSITIVE OPINION FROM CHMP FOR TRANSLARNA™ (ATALUREN)

by Admin 5/23/2014 1:28:00 PM
May 23, 2014

PTC THERAPEUTICS RECEIVES POSITIVE OPINION FROM CHMP FOR TRANSLARNA™ (ATALUREN)

- The first treatment for the underlying cause of Duchenne muscular dystrophy -

 

SOUTH PLAINFIELD, NJ – May 23, 2014 – PTC Therapeutics, Inc. (NASDAQ: PTCT) today announced that following its request for re-examination, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion regarding the company's application for a conditional marketing authorization of TranslarnaTM (ataluren) for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD) in ambulatory patients aged five years and older.

"We are very pleased with the outcome of the CHMP review of Translarna's marketing authorization application (MAA) and the level of engagement we experienced with CHMP members throughout the review process," said Robert J. Spiegel, M.D., Chief Medical Officer of PTC Therapeutics, Inc. "We are grateful to the patients, families, advocacy groups and physicians who have supported PTC Therapeutics through many years of research and development of Translarna. It is important to note that this journey continues through the completion of our Phase 3 Translarna confirmatory trial in nmDMD (ACT DMD) which is a high priority for PTC and the DMD community."

Dr. Craig McDonald, Professor of Physical Medicine and Rehabilitation at the University of California, Davis, who developed and validated the 6-minute walk test as a primary clinical endpoint in Duchenne muscular dystrophy (DMD) stated, "This is a historic day for the DMD community. Translarna is the first treatment for the underlying cause of nonsense mutation DMD to receive a positive opinion from the CHMP. The Phase 2b clinical trial provided strong evidence that Translarna slows disease progression as measured by the 6-minute walk test. A clinically meaningful 31.3 meter benefit in 6-minute walk distance, relative to placebo, was achieved in 48 weeks of treatment in patients five years and older and this was supported by positive trends in multiple secondary efficacy endpoints. In addition, in the prespecified group of patients with less than a 350 meter baseline 6-minute walk distance, a 68 meter benefit was observed in patients treated with 40 mg/kg Translarna given daily, relative to placebo. A conditional approval by the European Commission based on this positive opinion would allow children with nmDMD in the European Union to gain access to Translarna while PTC Therapeutics completes its ongoing confirmatory trial."

The CHMP opinion will form the basis for a European Commission (EC) decision as to whether to formally grant the conditional marketing authorization. The European Commission will review the positive opinion from the CHMP and generally delivers its final decision within three months. The conditional marketing authorization would authorize the company to market Translarna with unified labeling in the 28 countries that are Member States of the European Union, as well as European Economic Area members Iceland, Liechtenstein and Norway.

"We congratulate PTC Therapeutics on this landmark decision by the CHMP," stated Elizabeth Vroom, Chair of United Parent Project Muscular Dystrophy (UPPMD). "We applaud PTC for its dedication to the community and its perseverance in pursuing regulatory options to provide Translarna to patients as rapidly as possible. The company's pioneering work has paved the way and encouraged the scientific community to develop new therapies for DMD," she continued. "The EMA is to be commended for recognizing the great unmet need for novel treatments for this relentlessly progressive disease."

Filippo Buccella, President of Parent Project Italy and UPPMD board member, commented, "After thirty years since the discovery of the dystrophin gene, we are finally beginning to see a change in the landscape. For the first time in the history of Duchenne, we see the path to approval for a drug to treat the underlying cause of DMD. This positive result rewards the efforts of a company that has always believed in collaboration with patients and with clinicians. The perseverance of this community made it possible to realize a dream that can give hope to the boys affected with nmDMD in Europe. Our work as a community of patients is not yet finished and we will stand ready to participate with PTC in the ensuing stages of this process and, we hope, with many other companies with new therapies for Duchenne."

PTC requested a re-examination of the CHMP's negative opinion received in January 2014. The positive opinion is based on data and subsequent analysis submitted from a 48-week, 174-patient Phase 2b double-blind, placebo controlled trial which demonstrated that nmDMD patients treated with Translarna (40 mg/kg given daily) walked on average 31.3 meters farther than patients on placebo, as measured by the change in six-minute walk distance (6MWD) from baseline to Week 48. Patients receiving Translarna also demonstrated a slower rate of decline in ambulation, based on an analysis of time to 10 percent worsening in 6MWD. Safety results showed that Translarna was generally well tolerated. Serious adverse events were infrequent and none were considered to be related to Translarna. PTC's global Phase 3 ACT DMD clinical trial is ongoing with full enrollment expected mid-2014.

"The positive opinion from the CHMP recommending the conditional approval of Translarna in nonsense mutation Duchenne muscular dystrophy is a major milestone for the DMD community and we are extremely proud of this joint achievement in accelerating the access to Translarna for patients with nonsense mutation DMD," stated Stuart W. Peltz, Ph.D., CEO of PTC Therapeutics, Inc. "DMD is a progressive disease for which there are currently no approved treatment options. As previously disclosed, we expect to have all patients enrolled in our global Phase 3 ACT DMD by mid-2014. The outcome of this trial is critical for achieving full approval in the EU as well as the US. Assuming that the EC approves a conditional marketing authorization for Translarna in nmDMD, today's decision means that in parallel to this effort, we will be able to provide patients access to Translarna with the immediacy that DMD deserves."

Full Press release here



Santhera Pharmaceuticals (SIX: SANN) meets primary endpoint of Phase III DELOS study

by Admin 5/16/2014 6:41:00 PM

Liestal, Switzerland, May 13, 2014 - Santhera Pharmaceuticals (SIX: SANN) announces today that its Phase III DELOS study of orally administered Catena®/Raxone® (INN: idebenone) in patients with Duchenne Muscular Dystrophy (DMD) met the primary endpoint and achieved its primary objective of delaying the loss of respiratory function compared to placebo.

The Phase III, double-blind, placebo-controlled DELOS study randomized 65 DMD patients who were 10-18 years of age and who were not using concomitant corticosteroids. The study met the primary endpoint, the difference between Catena®/Raxone® and placebo in the change from baseline to week 52 in Peak Expiratory Flow (p=0.04). Peak Expiratory Flow is a measure of respiratory muscle strength, the decline of which is a major contributing factor to morbidity and mortality in DMD. Catena®/Raxone® (900 mg/day) was safe and well tolerated with adverse event rates comparable to placebo. Other endpoint analyses are ongoing and results of these will be disclosed shortly.

"We are thrilled by these results which are consistent with the findings of our Phase II DELPHI and DELPHI Extension studies," commented Thomas Meier, CEO of Santhera. "As acknowledged by clinicians and regulatory authorities, preservation of respiratory function is a major benefit for patients with DMD. On the basis of these results we will approach the US and European authorities for discussions on the most expeditious regulatory pathway to approval."

"I am very enthusiastic about the positive outcome for the DELOS trial. This is tremendously good news for patients with DMD since it indicates that Catena®/Raxone® can mitigate respiratory weakness and dysfunction," commented Gunnar Buyse, M.D., Ph.D., Professor of Child Neurology at the University Hospitals Leuven (Belgium) and Principal Investigator for the DELOS study.

Santhera holds global commercialization rights to the DMD program, which has been granted orphan drug designation and patent protection in the US and EU.

About Catena®/Raxone® as Treatment of Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy is one of the most common and devastating types of muscle de-generation and results in rapidly progressive muscle weakness. It is a genetic, degenerative disease that is inherited in an X-linked recessive mode with an incidence of approximately 1 in 3,500 live born males worldwide. DMD is characterized by a complete loss of the protein dystrophin, leading to cell damage, impaired calcium homeostasis, elevated oxidative stress and reduced energy production in muscle cells. This results in progressive muscle weakness and wasting and early morbidity due to respiratory failure. Idebenone is a synthetic short-chain benzoquinone and a cofactor for the enzyme NAD(P)H:quinone oxidoreductase (NQO1) capable of stimulating mitochondrial electron transport and supplementing cellular energy levels.

* * *

About Santhera 
Santhera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative pharmaceutical products for the treatment of orphan mitochondrial and neuromuscular diseases. Santhera develops Catena®/Raxone® as treatment for patients with Leber's Hereditary Optic Neuropathy (LHON), Duchenne Muscular Dystrophy (DMD) and primary progressive Multiple Sclerosis (ppMS), all of them areas of high unmet medical need with no current therapies. Santhera previously received temporary approval (cATU) for Raxone® in the treatment of LHON in France and has recently submitted a Marketing Authorization Application to the European Medicines Agency for the treatment of LHON in the European Union. For further information, please visit the Company's website www.santhera.com.

Catena® and Raxone® are trademarks of Santhera Pharmaceuticals.



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Sarepta Therapeutics Announces Plans to Submit New Drug Application to FDA for Eteplirsen for the Treatment of Duchenne Muscular Dystrophy by Year End 2014

by Admin 4/22/2014 2:34:00 AM

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Apr. 21, 2014-- Sarepta Therapeutics, Inc.(NASDAQ:SRPT), a developer of innovative RNA-based therapeutics, today announced it plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) by the end of 2014 for the approval of eteplirsen for the treatment of Duchenne muscular dystrophy (DMD). Eteplirsen is Sarepta’s lead exon-skipping drug candidate in development for the treatment of patients with DMD who have a genotype amenable to skipping of exon 51.

The plan to submit an NDA for eteplirsen by the end of 2014 is based on a guidance letter from the Agency that proposed a strategy regarding the submission of an NDA for eteplirsen under a potential Accelerated Approval pathway and served as the final meeting minutes for four meetings that took place between November, 2013 and March, 2014. The Agency stated that “with additional data to support the efficacy and safety of eteplirsen for the treatment of DMD, an NDA should be fileable,” and outlined examples of additional data and analysis that, if positive, will be important to enhance the acceptability of an NDA filing by addressing areas of ongoing concern in the existing dataset. Additionally, the Agency provided clear guidance on an open-label, historically controlled confirmatory study of eteplirsen, as well as initial guidance on a placebo-controlled study of one or more follow-on DMD drug candidates, which, like the open-label study, could also be considered an acceptable confirmatory study to verify the clinical benefit of eteplirsen in the event of an accelerated approval.

“As we announce our plan to submit an eteplirsen NDA by the end of 2014, we are very pleased with the detailed guidance that the FDA has provided us on a potential eteplirsen approval pathway and their support of a historically controlled eteplirsen confirmatory study,” said Chris Garabedian, president and chief executive officer of Sarepta Therapeutics. “We also appreciate that the FDA shares our urgency in dosing a broader base of eteplirsen patients and has encouraged us to begin the clinical program with our follow-on exon-skipping drugs as soon as possible.”
Based on the Agency’s guidance, Sarepta plans to initiate several additional clinical studies with eteplirsen later this year in exon-51 amenable genotypes. These studies will include a clinical trial with predefined efficacy endpoints for ambulatory patients between the ages of 7 to 16 years who can walk a minimum distance, and two additional clinical trials that will evaluate safety and biomarkers in DMD patients younger than 7 years and DMD patients who have advanced in their disease progression to a point they cannot walk a minimum distance or have become non-ambulant. Additionally, Sarepta plans to initiate a placebo-controlled study with one or more of its follow-on DMD exon-skipping drug candidates by the end of the year.

“We are excited to have guidance from the FDA that allows us to move quickly into additional clinical trials with eteplirsen to confirm our current understanding of eteplirsen’s safety profile, itseffect on dystrophin production, and its impact on clinical outcomes in DMD patients,” said Edward Kaye, M.D., senior vice president and chief medical officer of Sarepta Therapeutics. “We are particularly pleased that the FDA shares our interest in accelerating the clinical development of our follow-on exon-skipping drugs and we expect to initiate enrollment in this trial later this year.”

Sarepta plans to immediately take steps to initiate the additional eteplirsen clinical studies with the goal of beginning dosing in the confirmatory study in the third quarter, with dosing in the additional trials (i.e., younger and more advanced DMD patients) to begin later this year. Once available, detailed study eligibility criteria and clinical site information will be posted on www.ClinicalTrials.gov and Let’s Skip Ahead, an online resource center from Sarepta for the DMD community available at www.SkipAhead.com.
Excerpts from the FDA’s letter on an NDA filing included:

“…with additional data to support the efficacy and safety of eteplirsen for the treatment of DMD, described below, an NDA should be fileable (assuming other aspects of the submitted application meet applicable standards). As we are sure you appreciate, however, our willingness to consider an application for filing cannot be taken to suggest the outcome of our review. We also note that if the application is filed, you should expect public discussion of the NDA at an Advisory Committee meeting.”
The FDA outlined two potential pathways to accelerated approval:

“1. The clinical data from Study 201/202 [Phase IIb clinical trial program] on 6-minute walk could be considered a finding on an intermediate clinical endpoint that could have the potential to support accelerated approval.”
Related to this first pathway to Accelerated Approval, the Agency stated that they have “significant concerns regarding our ability to draw valid conclusions based on the Study 201/202 data with respect to walking performance and other data,” and identified areas relating to the interpretation of the existing data set that will be addressed as part of an NDA review once the NDA is filed.

“2. We have discussed the possibility of using a number of modalities to quantify dystrophin in muscle biopsies, and discussed how these biomarkers might be used as a surrogate endpoint(s) to support accelerated approval.”

In evaluating this pathway, the FDA expressed concerns about methodological problems in the assessments of dystrophin and, “remain skeptical about the persuasiveness of the (dystrophin) data” and, as a result, the Agency is “uncertain whether the existing dystrophin biomarker data will be persuasive enough to serve as a surrogate endpoint that is reasonably likely to predict clinical benefit." However, the Agency further states that if they “were to find the biomarker data to be adequate upon detailed review, however, they would have the potential to support accelerated approval.” To that end, the Agency proposed “a collaborative effort in which we will work to better understand the methods and analyses used for the existing biomarker data,” and “also work together on methods for the collection of additional data that could be more reliable.”
Furthermore, the Agency suggested that “another approach to demonstrating an effect of eteplirsen on dystrophin protein production would be to obtain a fourth muscle biopsy in patients who are continuing in Study 202,” which could serve to enhance the acceptability of an NDA filing and accelerated approval.

Under either potential application of the Accelerated Approval pathway, the FDA’s letter included comments expressing both a desire for more eteplirsen safety and efficacy data and a willingness to consider supplemental data in an NDA filing or during an NDA review (following the NDA filing) from the ongoing Study 202 and early safety and biomarker data from a confirmatory eteplirsen study. The Agency also encouraged Sarepta to collect safety and biomarker data with eteplirsen in a broader population of patients, including DMD patients who were younger, older and non-ambulant, and previously treated with drisapersen.
Additional excerpts from the FDA’s letter on the eteplirsen and follow-on exon-skipping drug confirmatory studies:
“…any accelerated approval [of eteplirsen] would necessitate confirmatory studies to verify the clinical benefit. Confirmatory studies should be underway at the time of approval.”

The FDA outlined two approaches for confirmatory trials and urged Sarepta to “initiate both of these trials as soon as possible.”
“1. A historically-controlled trial might be acceptable to confirm clinical benefit following accelerated approval.”
“2. A randomized, placebo-controlled trial of another PMO [phosphorodiamidate morpholino oligomer] with a similar mechanism of action, directed at a different exon (e.g., SRP-4053 or SRP-4045), with a demonstration of a correlation between dystrophin production and definitive clinical benefit on 6-minute walk or another measure, could provide confirmatory evidence of eteplirsen’s clinical benefit if approval were based on a surrogate endpoint.”
 

See link to original press release here 



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DART’s Phase 1b/2a Study to Determine Safety and Tolerability of Lead Drug Candidate, Help Validate New Endpoint for Future DMD Studies

by Admin 7/26/2013 10:05:00 PM

Cambridge, Mass.—July 15, 2013—DART Therapeutics Inc., an innovative, new-model biotechnology firm focused on developing therapies for Duchenne muscular dystrophy (DMD), has initiated a phase 1b/2a study of its lead drug candidate, HT-100 (delayed-release halofuginone). The phase 1b study (with a six-month 2a extension) in patients will determine the safety and tolerability of different, increasing doses of HT-100, and explore trends in a range of efficacy endpoints.

HT-100 is an orally available, small molecule drug candidate intended to reduce fibrosis and inflammation and promote healthy muscle fiber regeneration in boys with DMD. The phase 1b/2a clinical program will enroll 30 boys and young men with DMD, both ambulatory and non-ambulatory. Participating centers include University of California, Davis Medical Center (Sacramento, Calif.), Kennedy Krieger Institute, Johns Hopkins School of Medicine (Baltimore, MD), Washington University School of Medicine (St. Louis, MO), Cincinnati Children’s Hospital Medical Center (Cincinnati, Ohio) and Nationwide Children’s Hospital (Columbus, Ohio). DART expects to complete the study in mid 2014.

“Treating DMD requires a cocktail of therapies that will change over time,” said Gene Williams, CEO of DART Therapeutics. “We believe HT-100 could be a valuable part of this cocktail—even a mini-cocktail on its own—because it demonstrates potential to address many different aspects of the disease in parallel, which could make it an exceptionally important therapy for all boys living with DMD.”

DART’s study will include boys aged six through 20, an atypical age range that allows investigators to evaluate HT-100’s safety in a broad population as well as study its effect in different disease stages. Researchers will also evaluate a new endpoint that could make DMD studies faster, more precise, less expensive and inclusive of a larger group of boys. Presently, the six-minute walk (6MW) is the standard endpoint for DMD studies. However, the 6MW has shortcomings including variability and difficulty interpreting the clinical relevance of a given effect size. It also limits study participants to boys who can walk at a certain speed. There are no validated endpoints for very young boys with DMD. The proposed endpoint, electrical impedance myography (EIM), is a simple, non-invasive technique that can measure the health of a muscle and track its changes over time. As a validated endpoint for DMD, EIM would allow researchers to include a wide range of boys in studies and more effectively and rapidly understand how well a treatment is working to halt disease progression.

“Not only do we need several different categories of treatments for DMD—a therapeutic cocktail that might include different components depending on the stage of the disease—we also need new endpoints to improve the quality and speed of our clinical studies,” said Dr. Diana Escolar, Associate Professor of Neurology at Johns Hopkins School of Medicine’s Kennedy Krieger Institute, DART’s Chief Medical Officer and Study Director. “It is only through this two-pronged approach that we will succeed in our mission to make DMD a chronic, manageable disease instead of a fatal one.”



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Sarepta Therapeutics Announces Plans to Submit New Drug Application to FDA for Eteplirsen for the Treatment of Duchenne Muscular Dystrophy in First Half of 2014

by Admin 7/26/2013 10:01:00 PM

CAMBRIDGE, MA -- (Marketwired) -- 07/24/13 -- Sarepta Therapeutics, Inc. (NASDAQ: SRPT), a developer of innovative RNA-based therapeutics, today announced it plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the first half of 2014 for the approval of eteplirsen for the treatment of Duchenne muscular dystrophy (DMD). Eteplirsen is Sarepta's lead exon-skipping compound in development for the treatment of patients with DMD who have a genotype amenable to skipping of exon 51.

The decision to submit an NDA for eteplirsen in 2014 is based on productive interactions with the FDA in a meeting that occurred this week. That meeting was a follow-up to the FDA's review of two recently submitted summary documents that included data on dystrophin and clinical outcomes from the existing eteplirsen studies. The FDA stated in pre-meeting comments that the Agency is "open to considering an NDA based on these data for filing." The Agency, however, requested additional information related to the methodology and verification of dystrophin quantification. Sarepta believes the requests from the Agency can be addressed and incorporated into an NDA submission in the first half of 2014.

"We are encouraged by the feedback from the FDA and believe that data from our ongoing clinical study merits review by the Agency and will be sufficient for an NDA filing," said Chris Garabedian, president and chief executive officer of Sarepta Therapeutics. "We plan to work closely with the FDA to prepare an NDA submission in the first half of 2014 as we continue to prepare for our confirmatory study and our manufacturing scale up."

The Agency would not commit to declaring dystrophin an acceptable surrogate endpoint under the CFR 314 Subpart H Accelerated Approval pathway prior to an NDA filing and commented that a decision by the Agency to file "the NDA would not indicate that we have accepted dystrophin expression as a biomarker reasonably likely to predict clinical benefit. A filing would only indicate that the question merits review, and that we deem the data to be reviewable."

Sarepta anticipates submitting an NDA for eteplirsen in the first half of 2014; however, the exact timing of the submission will be dependent on further discussions and agreement with the FDA on the information needed for an acceptable filing. Sarepta also intends to have an End-of-Phase II meeting with the agency later this quarter to discuss the requirements for the Chemistry, Manufacturing, and Controls (CMC) section of the NDA.



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