FDA Prepares for a Golden Age in Gene Therapy


    Last week the Commissioner of the Food and Drug Adminstration (FDA), Scott Gottlieb, announced that he expects to see 40 new gene therapies approved by 2022. This comes from a recent MIT report which predicts cures in diseases like blindness, sickle cell anemia and hemophilia within 10 years. Gottlieb wants to push the agency to come up with six new guidance documents to help with development, manufacturing and approval process of gene therapies. Many of the guidance documents from the FDA currently being followed by biotech companies, such as our own, are already outdated and require re-thinking.

    The optimism of the FDA comes on the back of three recently approved gene therapy products (also mentioned in my previous blogs): Novartis’ Kymriah, a Car-T cell therapy for acute lymphoblastic leukemia (ALL), Gilead’s Yescarta, a Car-T cell therapy for adult B-cell lymphoma and Spark’s Luxturna, an AAV therapy for the treatment of a retinal disease resulting in blindness.

    Gottlieb stated that in contrast to traditional small molecule drug development, where most of the FDA review process is focussed on the clinical trials and relatively little is needed for developing the chemical product, gene therapy requires the opposite approach where a substantial amount of resources are needed to establish the gene therapy production process and less is needed to establish early clinical efficacy in a small number of patients. Part of the reason stems from the fact that gene therapy has so far been targeted to small patient populations with rare genetic disorders. However, with more than 7,000 different rare diseases that affect the country, tens of thousands of people could benefit from gene therapy.

    In a statement at Alliance for Regenerative Medicine’s Annual Board Meeting, Gottlieb detailed two aspects that need to be addressed if gene therapy is to see success in commercialization.
    (1) The gene therapy vector production process must be standardized through “continuous manufacturing”. Otherwise the current processes in place for making lentivirus and AAV will be too inefficient and will depend too heavily on academic laboratories. With improved financing in the coming years, it is hoped more of the smaller biotech companies can shift production reliance towards more established CROs.

    (2) The manufacturing paradigm of developing gene therapies must be restructured. It is often difficult for biotech companies to guide a gene therapy product from an early stage pilot process in the laboratory to a later stage clinical trial process that is used for commercialization.
    Technical advances will be needed to help scale up capabilities of companies to generate viruses from the laboratory level (which is non-GLP and non-GMP) to the clinical level (which requires GMP quality products).

    Gottlieb also announced that he expects to accept more uncertain gene and cell therapies through the FDA’s new accelerated approval pathway called Regenerative Medicine Advanced Therapy (RMAT) designation. RMAT was opened up under the 21st Century Cures Act as part of the FDA’s initiative to speed up reviews for both cell and gene therapy products intended to treat life threatening conditions. At the end of April this year there had already been 62 RMAT designations.

    With the closing of last week’s BIO 2018 convention, (one of the biggest annual deal-making conventions of the biotech business), the industry has been set ablaze by optimism for gene therapy developments. Can gene therapy do to rare genetic diseases what immunotherapy and antibody drugs did for cancer therapy and other common disorders? One can only wait to see what happens once the hubris settles.



    MIT Report: https://newdigs.mit.edu/sites/default/files/FoCUS_Research_Brief_2017F211v011.pdf



    Alliance Speech: https://www.fda.gov/NewsEvents/Speeches/ucm608445.htm

    RMAT: https://www.raps.org/news-and-articles/news-articles/2018/2/rmat-vs-breakthrough-vs-fast-track-companies-se