From the President's Desk: Inaugural Letter
By:
Jacques Galipeau, MD FRCP(C)
Don and Marilyn Anderson Professor in Oncology
Associate Dean for Therapeutics Development
University of Wisconsin School of Medicine and Public Health
You know cell & gene therapy (CGT) is in the ascendency when an Oscar-winning director releases a movie at the 2022 Tribeca film festival documenting the development of CAR-T cell therapy that stars amongst other luminaries, the immediate past president of ISCT – our own Bruce Levine! Other telltale signs of vigor to our cherished field of CGT is the manifest appetite of private venture capital for this technology class including recent investments north of $625 million sponsored by Fortune 500 entrepreneurs that complement the massive investments worldwide by nation states, pharma, funding agencies and philanthropy. Money follows opportunity and this is mirrored by the explosive year-over-year growth of ISCT membership – now topping more than 2500 members from 60 countries.
Our Society’s niche is unique, as it is predicated on the pragmatic aspect of development and deployment of CGT technologies writ large - agnostic of the clinical use case - where manufacturing, regulatory, scientific, commercial and ethics of use converge. Hence, distinct platforms ranging from MSCs to immune effector cells, iPS and gene embellishment technologies can co-exist conceptually as they all share common pinch points in securing regulatory approval and later successful clinical adoption. Nowhere else can you find these cats herded within a single knowledge-based organization.
That said, hard work by engaged ISCT members is needed to build upon the recent CGT successes and learning from past CGT deployment mishaps. I propose that a few guiding principles can animate our ISCT efforts in the next few years: impact on clinical outcomes and distributive justice – themes that I intend to champion during my term as President.
Technologically, CGTs are moving so fast in positive disruptive ways that we are quite literally building the plane as we are flying it in regards to pre-clinical and translational development of life altering therapies. Foreseeable advances would include practical off-the-shelf CARs, including for solid cancers; immune effector therapies for autoimmune disease; iPS meeting the clinical promise of replacement therapies for blindness, Parkinson’ and diabetes; “tuned” MSCs redeployed for their exosomal functionalities and so many more use cases in CGT… Our collective goal is to address catastrophic ailments with unmet medical needs where cell pharmaceutical attributes inarguably outshine anything medicinal chemistry and biologics have to offer. Our Society’s 40+ committees spanning the core membership of manufacturing, regulatory, commercial and scientific will be the organizing principle to reduce to practice these efforts. I enjoin all of you to reach out and connect with these committees as aligned with your interests and share your knowledge at ISCT meetings, regional and international.
A scholarly society’s companion journal also is an unimpeachable barometer of interest and relevance. Our crack team of editors have done a stellar job of growing Cytotherapy to a field leading position with a new impact factor of 6.196. In addition to impactful science, we are now the “go-to” journal for dissemination of international CGT guidance including contributions by WHO, ICCBBA as well as provocative thought leadership pieces from our international, regional and commercial representation. If you have presented a poster at one of our meetings, do follow through and submit the body of work for publication. If you are passionate about science, manufacturing, regulatory and ethical matters germane to CGT, post on our ISCT community website, post on ISCT Linkedin and aggregate colleagues and submit your editorial and position paper to the relevant ISCT committee (there are 40+!, so you’ll find likeminded colleagues within our organization).
Virtually all international jurisdictions have approved CGT pharmaceuticals and the list is growing rapidly. Post-marketing approval commercial success is on the horizon especially for platforms where economies of scale and centralized quality assurance ensure a margin-friendly deployment for the greater good. We need more and ISCT is the best meeting place for fertile ideas exchange optimizing commercial success and pre-clinical disruptive innovations. To this hub-and-spoke distribution model, CGTs are also amenable to decentralized distribution that would meet surging demand far and wide.
Indeed, place of care, vein-to-vein (POCV2V) manufacturing and deployment is a CGT development model oft used in early investigational clinical trial testing and is an attractive post marketing approval distributive model, especially for autologous or one donor/one recipient cell therapy strategies. Akin to autologous and allogeneic BMT but distinct due to its more-than-minimally-manipulated ATMP status, POCV2V CGTs face regulatory and commercialization headwinds that mitigate development of useful CGTs not readily amenable to traditional at scale centralized manufacture and distribution commercial paradigm. Our membership and goodly fraction of vendor clientele attracted by the ISCT value proposition provide CRO & CMO services, POC designed devices, as well as manufacturing and quality ancillaries predicated on the POCV2V deployment model. Major CGT regulatory jurisdictions such as Japan and South Korea have adopted risk-adapted conditional approval schemes to enhance patient access to promising POCV2V CGTs. FDA is now airing some reflections on risk-adapted approval models that will address patient access to effective CGTs and possibly mitigate some of the vexations that have befallen prior approved CGTs that ran afoul the shoals of post BLA pricing and reimbursement leading to post marketing business failures. In addition to championing the tried-and-true post approval model for commercialization of scalable CGTs, I do believe that ISCT need to continue promoting the critical conversation around the imperfect remedies of POCV2V facilities’ use of hospital exemption (Europe) and expanded access (USA) whilst mindful of risks of abuse by scoundrels preying on vulnerable subjects with unproven therapies. The reasoned use of multiple commercialization paths adapted to the platform risk, clientele medical need and pricing/reimbursement exigencies will allow for CGT distributive justice within and outside the wealthier regulatory jurisdictions.
ISCT has the wind in its sails as best exemplified by the astonishing success of our San Francisco international meeting last May. For all the reasons above, the passion of our membership and the engagement of our leadership team and Head Office, good things are on the horizon for the next few years. Let me close with a shout-out to the multitudes within our organization and membership that do things small and grand to advance CGTs for the betterment of human health outcomes and I do look forward seeing many of you in Paris May 2023.
Between now then, let’s have some fun improving lives through safe and effective cell and gene therapies.
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