echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Medical News > Medical World News > Can gene therapy break through the $10 billion hemophilia market?

    Can gene therapy break through the $10 billion hemophilia market?

    • Last Update: 2020-10-30
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com
    For Ryan Hallock, he can't have much physical movement, or even fall on his wrong arm or walk, and he bleeds.
    , Hallock used drugs to help stop the bleeding, but it didn't take long for the drugs to be useless to him.
    , he started experimenting with new experimental gene therapies, and so far he hasn't had any bleeding.
    , Hallock suffers from severe haemophilia, a rare genetic disorder.
    hemophilia patients are medically nicknamed "Glass Man" and even a careless bump or small wound in life can lead to fractures or even blood flow.
    of hundreds of thousands of haemophilia patients, Hallock felt the new hope that gene therapy had given him.
    "cure" may be a step closer.
    haemophilia is a group of hereditary hemorrhagic diseases with severe clotting dysfunction, which is caused by a lack of congenital clotting factors.
    lack of sufficient coagulation factors in the patient's body, blood in the damaged parts of the blood vessels can not normally coagulate, resulting in bleeding more than, and caused a series of symptoms.
    mainly A, B two types, of which type A haemophilia is the most common mode, about 80% of patients belong to this type.
    patients with type A haemophilia lacked a coagulant protein called coagulation factor VIII, while type B lacked clotting factor IX.
    addition, type A haemophilia is caused not only by genetic causes, but also by spontaneous genetic mutations.
    according to the proportion of blood clotting factor VIII, type A haemophilia can be divided into three stages: mild, moderate and severe.
    For a long time, type A haemophilia mainly takes the alternative treatment of clotting factor, but after treatment for a period of time, the patient's blood may produce coagulation factor VIII inhibitors, resulting in reduced effectiveness of treatment, and even severe intracranial bleeding.
    patients with type A haemophilia who had inhibitors in the body increased their risk of death by 70% compared to patients without coagulation factor VIII inhibitors.
    and gene therapy can prevent similar situations.
    the field of gene therapy for haemophilia, in addition to Roche's SPK-8011 and SPK-8016, Pfizer and Sangamo jointly developed the giroctocogene fitelparvovec (SB-525), Bio The valocococogene roxaparvovec (Roctavian) developed by Martin and bay2599023 (DTX201, AAVhu37 FVIII), developed in partnership with Ultragenyx Pharmaceuticals, are in clinical trials.
    amT-180 preclinical studies developed by UniQure also showed positive results.
    the global market for haemophilia ( mainly composed of haemophilia A and haemophilia B ) has exceeded US$10 billion and is expected to exceed US$15.1 billion in 2025 , with a compound growth rate of 4.5% in 17-25 years .
    a place in this battleground, if you can win the first product on the market, or you can occupy a place in the haemophilia market.
    shell society is now the major pharmaceutical companies for haemophilia gene therapy research progress is organized as follows.
    01 Roche and Spark TherapeuticsSPK-8011 are gene therapies based on the AAV virus vector conduction human factor VIII gene developed by Spark Therapeutics, a subsidiary of Roche.
    it can effectively transduce cells and express the factor VIII gene, endogenetic production factor VIII, which is missing in the B-domain optimized by cryptonots, so as to treat haemophilia type A;
    , Roche announced long-term follow-up data for SPK-8011, a gene therapy for type A haemophilia developed by Spark.
    data showed that in five patients who were initially treated with gene therapy, patients showed stable and long-lasting expression of FACTOR VIII, a 91% reduction in annual bleeding rate (ABR), less than 2% viII activity before treatment with SPK-8011, and 5.2%-19.8% in 2-3.3 years after treatment.
    that no decrease in the expression level of the coagulation factor VIII was found during follow-up for more than two years.
    Addition, Spark has developed another gene therapy, SPK-8016, based on AAV vector expression coagulation factor VIII, to restore normal blood clotting pathways by neutraling inhibitory antibodies and increasing the level or activity of coagulation factor VIII in patients.
    Currently, Spark is recruiting 30 patients with severe type A haemophilia (those with or without VIII factor inhibitors in their blood) for phase 1/2, multi-center, open-label and non-randomized clinical trials (NCT03734588).
    02 Pfizer and SangamoSB-525 are gene therapies based on recombined AAV2/6 vectors, developed by Pfizer and Sangamo.
    the therapy has improved the genetic modification of liver-specific initiators, coding factor VIII, as well as polyA and viral vector sequences, which can not only optimize the efficiency of carrier production, but also improve the expression of liver-specific factor VIII protein.
    June, Pfizer and Sangamo announced the results of a Clinical Study of Phase I/II Alta, a gene therapy for severe type A haemophilia, SB-525.
    results showed that SB-525 was generally well- resistant among the 11 subjects.
    patients with severe type A haemophilia who received a dose of 3e13 vg/kg showed continuous levels of viII factor (FVIII) activity, and the patient's moderate coagulation factor VIII activity level reached 64.2% of normal.
    all treatment-related elevations of transaminase (ALT) were controlled at low levels, and so far, none has been associated with a lack of factor VIII expression.
    addition, the FDA has awarded SB-525 advanced therapy (RMAT) for the treatment of haemophilia A regenerative medicine.
    follow-up Phase III clinical trials and IND work will also be led and conducted by Pfizer.
    03 BioMarin Roctavian is a gene therapy developed by BioMarin that uses a vector of AAV5 viruses to deliver functional copies of the coded coagulation factor VIII gene to patients.
    therapy can help patients restore their own coagulation factor VIII production capacity, to achieve the effect of treating type A haemophilia.
    but according to BioMarin, Roctavian's pricing is expected to be between $2 million and $3 million per treatment, and combined with market conditions, Roctavian could become a billion-dollar product.
    , BioMarin announced that it was updating the results of an open-label Phase I/II clinical study in Roctavian, a gene therapy for haemophilia.
    , the average APR for the fourth year of the 6e13 vg/kg group was 1.3, while the average ACR for the third year of the 4e13 vg/kg group was 0.5.
    over a one-year period, 6 out of 7 participants in the 6e13vg/kg group and 5 out of 6 participants in the 4e13 vg/kg group did not have spontaneous bleeding.
    four years, patients' use of factor VIII fell from 135.6 times a year to 5.4 times a year, a 96% decline.
    treatment with Roctavian, the decline in factor VIII activity levels was consistent with previous observations and remained within a range that could provide hemostectant effects.
    , the FDA rejected the gene therapy and asked BioMarin to provide more evidence that it has a long-term effect on bleeding rates.
    , according to current long-term research by BioMarin, the effect was highest in the first year or so after roctavian treatment, and then began to decline slowly.
    , it's still unknown whether the treatment will pass the review.
    according to BioMarin, the FDA wants two years of follow-up data for all patients in Roctavian's large study, which will not be completed until November 2021.
    addition, the treatment is not available to all patients with haemophilia A and needs to exclude those who produce antibodies to the AAV5 virus vector.
    , Roctavian has been granted breakthrough drug eligibility (BTD), priority drug eligibility (PRIME) by the EMA, and orphan drug eligibility (ODD) by the FDA and EMA.
    04 Bayer and Ultragenyx in August 2018, Bayer in collaboration with Ultragenyx developed a gene therapy for the treatment of haemophilia type A BAY2599023 (DTX201).
    DTX201 uses REGENXBIO's proprietary NAV AAVhu37 vector to transmit the coagulation factor VIII gene to liver cells, promoting its continuous expression, potentially overcoming defects in patients with haemophilia A.
    the gene therapy was originally developed by Dimension Therapeutics and subsequently reached a $252 million partnership with Bayer for co-development and commercialization.
    October 2017, Ultragenyx announced its $151 million acquisition of Dimension.
    Based on the results of the Phase I./II. clinical trial of DTX201, published at Bayer's annual meeting of the American Society of Hematology (ASH) in December 2019, DTX201 can safely and effectively raise the level of coagulation factor VIII (FVIII) and prevent or reduce bleeding in the first two patients with severe type A haemophilia in clinical trials.
    , DTX201 (AAVhu37 FVIII) is a carrier based on non-replicatable adenolyt-related virus (AAV) serotype hu37, which contains a single-stranded DNA genome that encodes FVIII missing from the B domain, which is usually genetically modified under the control of a combination of optimized liver-specific initiaters and enhancers.
    addition, AAVhu37 is a member of the liver-philic branch E family screened on the basis of non-clinical studies, which have shown effective liver-directed FVIII gene transfer, good biological distribution, and long-lasting FVIII expression.
    05UniQureAMT-180 is a gene therapy developed by UniQure for the treatment of type A haemophilia that can be used in patients with FVIII inhibitors in the body.
    the therapy uses an AAV5 virus vector to deliver a VARIANT mutant gene, obtained through random mutations and high-flux screening, called FIFA-FIAV, which can activate the blood clotting system on its own without relying on FVIII.
    UniQure is a pioneer in gene therapy, owning Glybera, the first gene therapy to be available in Europe.
    is working on gene therapy to cure rare diseases such as haemophilia, Huntington's disease and other serious genetic diseases at once.
    In May, UniQure published data from a preclinical study of its gene therapy, which showed that AMT-180 had good safety in mice and non-human primates, and that thrombosis risk markers tested showed that animals tested for the drug did not increase the risk of thrombosis by receiving the therapy.
    in mice and non-human primates showed significant dose dependence, and clotting activity did not depend on FVIII levels.
    a comprehensive view, the gene therapy mentioned above uses AAV virus vector to achieve the purpose of treatment, further indicating that the carrier is safe and effective, but at the same time should consider whether the patient produces antibodies to the vector, so as to avoid the production of adverse reactions.
    for patients, the success of any gene therapy for haemophilia will be significant, but long-term effectiveness, truly "once and for all" is the result we all expect.
    , it will also be a major test for drug companies to consider issues related to pricing and patient acceptance.
    .
    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.