Join our online Q&A on exon skipping

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  • #128690
    Reply To: Join our online Q&A on exon skipping

    Hi Emma, Prof Muntoni and Dr Kaye may be able to give you some information on recruitment plans for the upcoming trial

    Hi Professor Muntoni, I saw your reply to Ms Calvert, our 5 year son has the same deletion requiring exon skipping 53. Would it be possible for him to be included in the Sarepta trials when they become available if we live in the UK?

    Kind Regards

    Muscular Dystrophy UK staff member

    Alexa Follen
    Moderator
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    Joined: 12/05/2015
    #128691
    Reply To: Join our online Q&A on exon skipping

    The FDA were critical of methods used for biomarkers and clinical outcomes. How will future trials address these issues? Please see my previous post

    In the process of developing a drug for a new disease indication such as muscular dystrophy, there are always challenges in developing surrogate and clinical endpoints. We are working on developing newer and more sensitive measures to measure dystrophin in muscle. We are also exploring new biomarkers that could be obtained from the serum or urine that would be easier for patients. We are looking at a number of exploratory clinical trial endpoints, but at present 6MWT remains the most reliable and validated clinical endpoint.

    Dr Ed Kaye, CEO, Sarepta Therapeutics

    Dr Ed Kaye
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    #128692
    Reply To: Join our online Q&A on exon skipping

    Hi
    nice to hear from you.
    This is a complex question and the space for a complex awser is not there!. Different studies have had different issues, one that is currently precluding the use of eteplirsen in Europe is one that I hope will be resolved this year. This is to do with a patent dispute that precludes the use of this drug in Europe although it was originally developed in Europe. Whether advocacy groups can influence the outcome of these disputes or not I dot frankly know.

    Professor Francesco Muntoni, Director, Dubowitz Neuromuscular Centre, Great Ormond Street Hospital

    Professor Francesco Muntoni
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    #128694
    Reply To: Join our online Q&A on exon skipping

    As for Summit drug, this will need to be evaluated in the protocol when the protocol will be finalised. I am nto aware this has been finalised so far re: inclusion/ exlusion criteria

    Professor Francesco Muntoni, Director, Dubowitz Neuromuscular Centre, Great Ormond Street Hospital

    Professor Francesco Muntoni
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    #128696
    Reply To: Join our online Q&A on exon skipping

    Thanks to Professor Muntoni and Dr Kaye for all your answers so far. We have five more minutes if there are more questions!

    Muscular Dystrophy UK staff member

    Alexa Follen
    Moderator
    Posts: 32
    Joined: 12/05/2015
    #128697
    Reply To: Join our online Q&A on exon skipping

    All children eligible for a clinical trial will be given consideration. There are issues regadring trial capacity at each of the trial sites, but as in UK we have recruited a number of exon 53 skippable children in the ongoing SKIP NMD, we should have the opportunity in the trail sites that will eventually open, to recruit new children not currently involved in exon 53 clinical trials

    Professor Francesco Muntoni, Director, Dubowitz Neuromuscular Centre, Great Ormond Street Hospital

    Professor Francesco Muntoni
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    Joined: 05/05/2016
    #128698
    Reply To: Join our online Q&A on exon skipping

    The FDA were critical of methods used for biomarkers and clinical outcomes. How will future trials address these issues? Please see my previous post

    In the process of developing a drug for a new disease indication such as muscular dystrophy, there are always challenges in developing surrogate and clinical endpoints. We are working on developing newer and more sensitive measures to measure dystrophin in muscle. We are also exploring new biomarkers that could be obtained from the serum or urine that would be easier for patients. We are looking at a number of exploratory clinical trial endpoints, but at present 6MWT remains the most reliable and validated clinical endpoint.

    The FDA cited in the briefing document for Eteplirsen that “The lack of an effect with the higher dose group tends to undermine the finding in the lower dose group”. Is it possible that the lack of effect in the higher dose range could be attributed to an increased activation of endogenous miRNA pathways leading to post-transcriptional gene silencing? Is Sarepta currently investigating methods to mitigate RNAi pathways that may lead to an adjuvant therapy to increase exon skipping effectiveness?

    Shouldn’t preliminary evidence indicating any increase (even 0.9%) in dystrophin be considered “substantial” over current therapies and therefore meet the threshold for breakthrough therapy designation under FDASIA?

    At the present time, we don’t have a full understanding of the miRNA pathways that may be involved in the dystrophin gene pathway. Based on our pharmacodynamic assessment obtained through clinical trials, 30 mg/kg is the recommended dose.

    While a minimal clinically threshold for dystrophin has not been established, we demonstrated a significant increase in dystrophin following treatment for at least 6 months. It will be determined by the FDA whether this meets guidelines established for regulatory approval.

    Dr Ed Kaye, CEO, Sarepta Therapeutics

    Dr Ed Kaye
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    #128699
    Reply To: Join our online Q&A on exon skipping

    Claire O’Hanlon from Northern Ireland also had a second question for Sarepta:

    What will the minimum age for eligibility for the exon 45 skipping trial in Europe? Most other exon skipping trials I’ve seen tend to have a minimum age of 6 or 7, will this still be the case or will accelerated approval of eteplirsen help in anyway to reduce the minimum age to 5?

    Dr Jenny Sharpe, Research Communications Manager at Muscular Dystrophy UK

    Jenny Sharpe
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    #128700
    Reply To: Join our online Q&A on exon skipping

    It was nice to “hear ” from you, From Ed, and also from all the families and also some DMD individuals. Have a good evening. Francesco Muntoni

    Professor Francesco Muntoni, Director, Dubowitz Neuromuscular Centre, Great Ormond Street Hospital

    Professor Francesco Muntoni
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    #128701
    Reply To: Join our online Q&A on exon skipping

    Claire O’Hanlon from Northern Ireland also had a second question for Sarepta:

    What will the minimum age for eligibility for the exon 45 skipping trial in Europe? Most other exon skipping trials I’ve seen tend to have a minimum age of 6 or 7, will this still be the case or will accelerated approval of eteplirsen help in anyway to reduce the minimum age to 5?

    Minimum age is 6 years old for the exon 45/ 53 trial.

    Dr Ed Kaye, CEO, Sarepta Therapeutics

    Dr Ed Kaye
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    #128702
    Reply To: Join our online Q&A on exon skipping

    Hi again, Leslie here

    For the next Exon 53 trials, what is the criteria on age?. Could my 11, probably 12 by then, be eligible?

    Leslie

    Twinless
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    Joined: 10/05/2016
    #128703
    Reply To: Join our online Q&A on exon skipping

    For the next Exon 53 trials, what is the criteria on age?. Could my 11, probably 12 by then, be eligible?

    Leslie

    Twinless
    Participant
    Posts: 0
    Joined: 10/05/2016
    #128704
    Reply To: Join our online Q&A on exon skipping

    It was nice to “hear ” from you, From Ed, and also from all the families and also some DMD individuals. Have a good evening. Francesco Muntoni

    We appreciate all the interest of the patient groups in exon skipping. We hope we were able to respond to your questions.
    Have a very great evening! :ty:

    Dr Ed Kaye, CEO, Sarepta Therapeutics

    Dr Ed Kaye
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    #128705
    Reply To: Join our online Q&A on exon skipping

    Thanks everyone for your questions, and to Professor Muntoni and to Dr Kaye for their time this evening.

    We’ll be joined Professor Dame Kay Davies next week for a discussion on utrophin upregulation, so hope to see you there!

    Muscular Dystrophy UK staff member

    Alexa Follen
    Moderator
    Posts: 32
    Joined: 12/05/2015
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