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A Leap Forward: Spark Therapeutics Seeks FDA Approval for its Vision-Restoring Gene Therapy

Gene therapy recipient Yannick DuweWe’re approaching a critical milestone in the fight against blinding retinal diseases, and it has the potential to tremendously boost and accelerate the advancement of virtually all gene therapies in development for dozens of inherited retinal diseases.

Sometime in 2016, Spark Therapeutics will request marketing approval from the U.S. Food and Drug Administration (FDA) for its landmark gene therapy for retinal conditions caused by mutations in the gene RPE65, namely certain forms of Leber congenital amaurosis and retinitis pigmentosa.

The request, formally known as a biologics license application, or BLA, comes on the heels of Spark’s announcement earlier this week that its Phase III trial of the treatment has delivered positive “top-line” results. Among other results, participants, after treatment, significantly improved their ability to navigate a mobility course in dim and bright settings. These individuals, who range in age from 4 to 44, were virtually blind before receiving the therapy.

There are no guarantees that the treatment will be approved, but given the clinical-trial safety and efficacy data reported over the last eight years, we have good reason to be cautiously optimistic. Approval would likely make it the first FDA-approved gene therapy for an eye disease or an inherited condition.

While FDA approval would obviously be great news for people with RPE65 mutations, the regulatory nod is strong affirmation to researchers and biotech companies around the world that gene therapies are a scientifically and commercially viable approach to fighting blindness and possibly other genetic diseases and cancer.

Gene therapy recipient Allison Corona

LCA gene therapy recipients include Yannick Duwe, top, and Allison Corona, above. (Photo of Yannick courtesy of ARVO.)

It wasn’t long ago that gene therapy seemed like science fiction. Could we really develop a human-engineered virus to deliver healthy, vision-restoring genes to the retina? Could it be administered through a single retinal injection that would work for several years? Many experts had their doubts, seeing as the approach was so cutting-edge. However, the Foundation Fighting Blindness was compelled to drive gene-therapy research because of its strong potential to save and restore vision for people with inherited retinal conditions. And drive, we did.

While the gene-therapy story began more than 20 years ago, we reached a major turning point in 2001, when the treatment restored vision in blind Briard dogs with LCA, including the overnight media sensation Lancelot. The success in canines opened the door in late 2007 to clinical trials at The Children’s Hospital of Philadelphia and several other institutions, and, today, a thriving biotech is knocking on the door of the FDA for marketing approval.

RPE65 was a strategic disease target for retinal gene therapy development because, technically, it was “low-hanging fruit,” meaning it was easier to treat than other conditions. But with this disease hopefully under our belt soon, we’ll be well-poised to advance gene therapies for a variety of other retinal degenerations, including choroideremia, Usher syndrome, Stargardt disease, retinoschisis, retinitis pigmentosa and achromatopsia. With optogenetics therapies, which are now just moving into clinical trials, we even have the potential to restore vision in someone who is completely blind from a retinal disease, and for whom a genetic cause has not been identified.

Of course, a lot of work remains to develop treatments for the entire spectrum of complex retinal diseases. But FDA approval for the LCA (RPE65) gene therapy would be a giant leap forward in getting vision-saving gene therapies to everyone who urgently needs them.


29 Responses to 'A Leap Forward: Spark Therapeutics Seeks FDA Approval for its Vision-Restoring Gene Therapy'

  1. pradeep meinam says:

    it’s a great job .hope spark therapeutic will give rebirth to many lives.hope FDA approves soon.

  2. Irv Arons says:

    For the latest information on the status of the clinical trials for several retinal diseases, please take a look at my just published article: “What’s New in Gene Therapy for Ophthalmology”, online now in the October issue of Retinal Physician (link: http://tinyurl.com/RetPhys-GT-Update)

    Irv Arons

  3. maid goussous says:

    I hope one day I can treat my daughter from LCA disease. In affordable way.

  4. Vicki Chapman says:

    I would love to have my son in this study. He has Retinal Rod/Cone Dystrophy with Nystagmus.

    • EyeOnTheCure says:

      To participate in the Spark LCA trial, your son must have a genetic diagnosis for LCA caused by mutations in the RPE-65 gene. Accordingly, your son should consider genetic testing to try and identify the mutant gene responsible for causing the disease. If the gene is identified, medical databases such as PubMed can be searched to identify any research that is being conducted on the gene or protein. With a molecular diagnosis, he may qualify one of the gene therapy trials that are taking place, including the RPE-65 gene therapy trial (if he has a mutation in this gene). For information on genetic testing, please see the following web link to download a PDF document: http://www.blindness.org/sites/default/files/pages/pdfs/Genetic-Testing-Booklet-V5.2-20151023.pdf
      Whether his disease gene is identified or not, he should still consider participating in FFB’s “My Retina Tracker”, a free registry that monitors clinical trials that are recruiting for various retinal diseases. For more information on “My Retina Tracker” please see the following web link:
      https://www.myretinatracker.org/

  5. Jon Smith says:

    Hello Dr Steve Rose,

    I notice that various degenerative diseases are mentioned above. Could you please tell me if this would also include treatment for Best’s disease ?

    Thanks

  6. David Thomas says:

    This is a great step forward. We are all hoping this leads to a treatment for CHM for my son and so many others. Please FDA, we need this.

  7. balaurugan says:

    i am waiting for many years to hear this good news.I hope that FDA will give approval to save many chindren life

  8. Warren W Watson says:

    This is wonderful news. Our daughter lost her vision to Lebers. (LHON) over 5 years ago. Hopefully this will have positive results for LHON also. Keep up the super work!

  9. Jim Wilson says:

    What about treatment for retinas damaged by a detachment?

    • EyeOnTheCure says:

      Please see the following link to the National Eye Institute’s page on retinal detachment:
      https://nei.nih.gov/health/retinaldetach/retinaldetach

    • J.Perrodin says:

      My brother and I are middle aged and our mobility is very limited. we are praying this gets approval for our RP. Would be willing to participate in research.

      • EyeOnTheCure says:

        The gene therapy being developed by Spark as well as other academic and private groups is very specific. Accordingly you and your brother should consider genetic testing to try and identify the mutant gene responsible for causing the disease. If the gene is identified, medical databases such as PubMed can be searched to identify any research that is being conducted. With a molecular diagnosis, one may also qualify for gene therapy trials that are taking place. For information on genetic testing, please see the following web link to download a PDF document:
        http://www.blindness.org/sites/default/files/pages/pdfs/Genetic-Testing-Booklet-V5.2-20151023.pdf

        Whether the disease gene is identified or not, one should still consider participating in FFB’s “My Retina Tracker”, a free registry that monitors clinical trials that are recruiting for various retinal diseases. For more information on “My Retina Tracker” please see the following web link:
        https://www.myretinatracker.org/

        It may also be helpful to periodically check the website: http://WWW.CLINICALTRIALS.GOV which is maintained by the National Institutes of Health and contains a searchable list of clinical trials for most known diseases. Each clinical trial listing will provide you with information on what the study is about, the requirements for participating and contact information. I hope you find this information helpful.

    • Lola Davis says:

      Dr. Henry Klassen, UC at Irvine is having tremendous success with stem cell treatment that may have broad application for rod and cone degeneration. His research is another area well worth keeping in mind.

  10. Marion. Scott says:

    I have two sons with choroideremia. When do you think the gene therapy will be available to the public? Time is of the essence. Thank you for all of the wonderful work that you do,thank God!

  11. Katey says:

    I am a mother broker heart for her son has RP. This news made me smile and cry at the same time. I want to say thank you so much for the job you do to help us.. God bless you all

  12. Travis says:

    My nieces is 13 yrs old and she has Leber congenital amaurosis and I was wondering if their are any trails into a cure for her type of blindess and how can we register her for any.

  13. Muhammad says:

    My son has cone Rod Dystrophy. He has ABCA4 Gene mutation.

    I wanted to know if this therapy will help ?

    Kindest Regards

    • EyeOnTheCure says:

      Muhammad, you will be pleased to know that the Foundation Fighting Blindness is partnering with Sanofi Pharmaceuticals on a gene therapy clinical trial for Stargardt disease or cone rod dystrophy caused by mutations in ABCA4. For more information on this trial, see the following link:
      http://clinicaltrials.gov/ct2/show/NCT01367444?term=stargardt&recr=Open&no_unk=Y&rank=2 In order to participate in this or any other gene therapy trial, you must first obtain a molecular (genetic) diagnosis. For information on genetic testing, please see the following web link to download a PDF document: http://www.blindness.org/sites/default/files/genetic_testing_booklet_201311rev.pdf

      You should also consider enrolling in “My Retina Tracker”, a free registry that helps link people with retinal disease to appropriate clinical trials that are recruiting. For more information on “My Retina Tracker” please see the following web link: https://www.myretinatracker.org/

      Of general interest, there is a “Stargardt – Macular Degeneration” Facebook page where people can communicate with other people affected by Stargardt disease. Here is the link: https://www.facebook.com/groups/Stargardts/

      Finally, below is a list of pharmaceutical companies that are developing therapies for Stargardt Disease:

      Acucela,( http://www.acucela.com/) is a Seattle-based biotechnology company that is developing several drugs for retinal diseases such as AMD, dry eye, diabetic retinopathy, retinopathy of prematurity and Stargardt disease. Acucela’s visual cycle modulators (VCM) reduce the activity of the rod visual system — in essence, “slowing it down” and reducing the metabolic load on the retina. Reducing the speed of the visual cycle has been shown to protect the retina from light damage and reduce the accumulation of retinal-related toxic by-products, including A2E, which is implicated in both Stargardt disease and dry AMD. The Company’s lead investigational compound (Emixustat™) is currently in Phase 3 trials for dry AMD. Once approved by the FDA, Emixustat could be prescribed for Stargardt disease.

      Ocata Therapeutics (https://www.ocata.com/), a Santa Monica-based biotechnology company, has developed an RPE cell line that is derived from embryonic stem cells (ESC). Studies have shown that the subretinal transplantation of ESC-RPE cells in a rat RP model resulted in 100% visual function rescue. Functional rescue was also achieved in the Stargardt mouse model with near-normal functional measurements recorded at more than 70 days. The RPE cell transplantation studies are now in Phase 2 human clinicals. Here is the link to the Clinical Trials.Gov recruitment web page: http://www.clinicaltrials.gov/ct2/show/NCT01469832?term=advanced+cell+technology&rank=2
      *Note: It is not known how long the transplanted RPE cells will last in a human patient with Stargardt disease. Unless gene or pharmaceutical-based augmentation treatment is coupled to the RPE transplant, toxic A2E will continue to be produced and eventually kill the RPE cells.

      Alkeus, (http://alkeus.com/) Alkeus has developed a form of vitamin A that upon light interaction, does not form toxic vitamin A metabolites and A2E. Alkeus’ lead compound, ALK-001, is an oral compound with a well-understood mechanism of action. ALK-001 was specifically designed to treat Stargardt disease by preventing the formation of these toxic vitamin A dimers in the eye. Alkeus is currently recruiting patients for a Phase 2 human clinical trial. Here is the link to the clinical trials.gov recruitment page: https://www.clinicaltrials.gov/ct2/show/NCT02402660

      Vision Medicine (Previously Visum) The Foundation Fighting Blindness is partnering with Vision Medicine to develop a small molecule therapy Stargardt disease. Vision Medicine’s novel approach proposes to develop drugs that will temporarily control levels of A2E in the eye and preserve the natural vision cycle, leading to a therapeutic treatment. Vision Medicine has discovered a unique chemical approach to sequester rather than eliminate A2E. Through this process, 25 diverse FDA approved drugs demonstrating both mechanistic and in vivo efficacy have been identified. Vision Medicine has identified a lead compound, VM 200, which is an enantiomer of an FDA approved drug that demonstrates complete retinal protection in preclinical studies. Vision Medicine plans to conduct Phase I and Phase II clinical trials in the near future.

      To read more about the partnership between Vision Medicine and FFB, see the following web link:
      http://www.blindness.org/foundation-news/foundation-fighting-blindness-partners-vision-medicines-develop-stargardt-disease

  14. JoAnne Glaude 1 808 258 1063 says:

    Hello, I have had RP (retinitis pigmentosa) since birth and I am now 61. I was wondering how the FDA approval process is coming along . Sure hope it can be speeded up as there are over 300 million with some form of RP on the planet. Many are totally blind now. This is HOPE for all.

    Appreciate knowing the status of FDA approval for the RP65 gene therapy..

    In Gratitude, JoAnne
    email: athenastar808@gmail.com

    • EyeOnTheCure says:

      Dear JoAnne, You should consider genetic testing to try and identify the mutant gene responsible for causing the disease. If the gene is identified, medical databases such as PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) can be searched to identify any research that is being conducted. With a molecular diagnosis, one may also qualify for gene therapy trials that are taking place. For information on genetic testing, please see the following web link to download a PDF document:
      http://www.blindness.org/sites/default/files/genetic_testing_booklet_201311rev.pdf

      Whether your disease gene is identified or not, you should still consider participating in FFB’s “My Retina Tracker”, a free registry that monitors clinical trials that are recruiting for various retinal diseases. For more information on “My Retina Tracker” please see the following web link:
      https://www.myretinatracker.org/

      You may also find it helpful to periodically check the website: http://WWW.CLINICALTRIALS.GOV which is maintained by the National Institutes of Health and contains a searchable list of clinical trials for most known diseases. Each clinical trial listing will provide you with information on what the study is about, the requirements for participating and contact information. Thank you for your support that is helping to accelerate the development of new safe and effective treatments for inherited retinal disease. I hope you find this information useful.

  15. Namit Sehgal says:

    With US approval, will you be treating Stargardt Disease as well next year or still genes Therapy not ready for Stargardt Disease?

    • EyeOnTheCure says:

      Dear Namit, You will be pleased to know that the Foundation Fighting Blindness is partnering with Sanofi Pharmaceuticals on a gene therapy clinical trial for Stargardt disease. For more information on this trial, see the following link:
      http://clinicaltrials.gov/ct2/show/NCT01367444?term=stargardt&recr=Open&no_unk=Y&rank=2 In order to participate in this or any other gene therapy trial, you must first obtain a molecular (genetic) diagnosis. For information on genetic testing, please see the following web link to download a PDF document: http://www.blindness.org/sites/default/files/genetic_testing_booklet_201311rev.pdf

      You should also consider enrolling in “My Retina Tracker”, a free registry that helps link people with retinal disease to appropriate clinical trials that are recruiting. For more information on “My Retina Tracker” please see the following web link: https://www.myretinatracker.org/

      Of general interest, there is a “Stargardt – Macular Degeneration” Facebook page where people can communicate with other people affected by Stargardt disease. Here is the link: https://www.facebook.com/groups/Stargardts/

      Finally, below is a list of pharmaceutical companies that are developing therapies for Stargardt Disease:

      Acucela,( http://www.acucela.com/) is a Seattle-based biotechnology company that is developing several drugs for retinal diseases such as AMD, dry eye, diabetic retinopathy, retinopathy of prematurity and Stargardt disease. Acucela’s visual cycle modulators (VCM) reduce the activity of the rod visual system — in essence, “slowing it down” and reducing the metabolic load on the retina. Reducing the speed of the visual cycle has been shown to protect the retina from light damage and reduce the accumulation of retinal-related toxic by-products, including A2E, which is implicated in both Stargardt disease and dry AMD. The Company’s lead investigational compound (Emixustat™) completed Phase 3 trials for dry AMD in June 2016. Unfortunately, the drug failed to slow lesion growth in over 500 patients with geographic atrophy, a form of dry AMD. Because of a strong demonstration of efficacy in the Stargardt mouse model, Acucela is considering initiating a study to explore potential benefits of Emixustat in patients with Stargardt disease.

      Astellas Pharma (https://www.astellas.us/ ) acquired Ocata Therapeutics in May of 2016. Headquartered in Marlborough, Massachusetts and supported by a research team in Tsukuba, Japan, Astellas serves as a global hub for regenerative medicine and cell therapy research in ophthalmology and other therapeutic areas that have few or no available treatment. At the present time, the RPE transplantation studies have been completed and the Phase 3 trial has yet to be announced. http://www.clinicaltrials.gov/ct2/show/NCT01469832?term=advanced+cell+technology&rank=2

      Alkeus, (http://alkeus.com/) Alkeus has developed a form of vitamin A that upon light interaction, does not form toxic vitamin A metabolites and A2E. Alkeus’ lead compound, ALK-001, is an oral compound with a well-understood mechanism of action. ALK-001 was specifically designed to treat Stargardt disease by preventing the formation of these toxic vitamin A dimers in the eye. Alkeus is currently recruiting patients for a Phase 2 human clinical trial. Here is the link to the clinical trials.gov recruitment page: https://www.clinicaltrials.gov/ct2/show/NCT02402660

      Vision Medicines (Previously Visum) The Foundation Fighting Blindness is partnering with Vision Medicine to develop a small molecule therapy Stargardt disease. Vision Medicine’s novel approach proposes to develop drugs that will temporarily control levels of A2E in the eye and preserve the natural vision cycle, leading to a therapeutic treatment. Vision Medicine has discovered a unique chemical approach to sequester rather than eliminate A2E. Through this process, 25 diverse FDA approved drugs demonstrating both mechanistic and in vivo efficacy have been identified. Vision Medicine has identified a lead compound, VM 200, which is an enantiomer of an FDA approved drug that demonstrates complete retinal protection in preclinical studies. Vision Medicine plans to conduct Phase I and Phase II clinical trials in the near future.

      To read more about the partnership between Vision Medicine and FFB, see the following web link:
      http://www.blindness.org/foundation-news/foundation-fighting-blindness-partners-vision-medicines-develop-stargardt-disease
      Thank you for your support that is helping to accelerate the development of new safe and effective treatments for inherited retinal disease.

  16. Alieu Kamara says:

    I have a feeling that FDA will approve the Gene Therapy treatment for people with LCA or IRD. Thanks to Spark Therapeutics for trying to resolve our problem. Special thanks to Foundation Fighting Blindness for all of their assistance to the blind community. You will receive blessing for your hard work to save humanity. Wow, I’m just waiting for the day that ST will call on me for my treatment. Can’t imagine what it will feel like!

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