by
Jacques Galipeau, MD, MD FRCP(C)
President, ISCT
Associate Dean for Therapeutics Development
University of Wisconsin School of Medicine and Public Health
There wasn’t a dull moment in 2023 for Cell & Gene Therapy (CGT) aficionados and the ISCT has been riding this bull run with gusto. Patricia Rocco (ISCT Global Secretary) reports that our Society’ membership sailed past a third thousand – a 28% increase since 2022! This is mirrored by record attendance at Paris, Perth and Houston meetings – including numerous partnered showings in Asia, South & Central America and Europe. Cytotherapy relaunched with the hire of Edwin Horwitz as the new Editor-in-Chief and an expanded Editorial board for its next phase of growth. Add a pinch of partnered inaugural Workforce development initiatives, and we’re just starting!
A few notable ISCT regional shout outs for ’23:
Milena Soares (South and Central America Regional VP) is appropriately proud of their April ’23 SCA Regional Town Hall, with a total of 244 registrants and 65 who had joined for the live broadcast. Ditto for their October ’23 Webinar focused on CAR-T: Historical perspectives, manufacturing and clinical applications. Finally, much local pride for the ISCT Trailblazer Award for Emerging Markets received by Ecuadorean Andres Caicedo at the Paris ’23 meeting.
From Patrick Hanley’s (North America Regional VP) standpoint, the highlight of the NA region the September ’23 ISCT NA meeting in Houston was a strong emphasis on point of care manufacturing. A similar sense of mission accomplished is telegraphed by Zlatibor Velickovic (Australia New Zealand Regional VP) for the extremely successful August ’23 ISCT ANZ meeting in Perth with strong engagement by local government in the furtherance of health center manufactured and distributed Cell & Gene Therapy (CGT) products. William Hwang (Asia Regional VP) and regional team also brokered a very successful ISCT partnered pre-conference at the Singapore Cell & Gene Therapy meeting in August ’23.
Anthony Ting (ISCT CCO – Chief Commercialization Officer) reminds us that ’23 was a technological banner year for commercial CGT developers with now more than 6 approved CAR-T products (the first granted in 2017) and the groundbreaking FDA/MHRA approval of the first CRISPR gene edited product - Vertex/CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel). Another first in class was the first approved cell product for T1D - CellTrans’ donislecel allogeneic pancreatic islet cell therapy, under the name Lantidra. Of note, Lantidra also breaks new ground as the first approved ATMP entirely manufactured at place-of-care, namely University of Illinois in Chicago. Tony does also highlight meaningful FDA approvals in the gene therapy space with beremagene geperpavec (B-VEC), for the treatment of dystrophic epidermolysis bullosa in patients 6 months or older (Krystal Biotech) and BioMarin’s valoctocogene roxaparvovec (val-rox) for the treatment of adults with severe hemophilia A. Also, big pharma is back at the table with acquisitive deals – AstraZeneca (Quell, Cellectis), Lily (Sigilon), Novo Nordisk (Life Edit).
With the good comes some stumbles, especially for commercial developers of MSCs as living therapeutics where FDA denied BLA approvals of Mesoblast’ Ryoncil (remestemcel-L) for pediatric steroid-refractory acute graft versus host disease for the second time as well as Brainstorm’ BLA application for NurOwn technology platform (autologous MSC-NTF cells) in ALS. Adding further vexation was Takeda’ announcement in October ’23 of the negative outcome of ADMIRE-CD II Trial of Alofisel (darvadstrocel) in Complex Crohn’s Perianal Fistulas that was to serve as the basis for Alofisel’ approval by FDA in USA. Notwithstanding, important technological strides in the MSC space are advancing including use of iPSC derived MSCs (Cynata) and most notably the explosive interest in developing MSC-derived extracellular vesicles (EVs) as a stand-alone pharmaceutical.
Fermin Sanchez-Guijo (Europe Regional VP) likes to point out that Europeans march to their own drummer with the Netherlands approving and funding hospital manufactured autologous TILs for melanoma and Spaniards on track to do same with their own bespoke place-of-care manufactured CD19-targeted CAR-T platform.
Bonjour ’24!
ISCT CEO Queenie Jang reminds us of all the upcoming May ’24 ISCT Vancouver meeting where east meets west in the most hospitable Canada with a terrific program put together by meeting co-chairs Sowmya Viswanathan, Dan Weiss and Aby Mathew. Emily Blyth (ANZ regional VP-elect) will be hosting her first ISCT ANZ regional conference to be held in Queenstown, New Zealand August ’24, ditto for Fermin Sanchez-Guijo also is banking on a ISCT EU meeting success in Gothenburg, Sweden September ’24. Asia Regional Vice-President, William YK Hwang invites you to join us in Singapore in July for the CGT Pan Asia Summit organized in Partnership with ISCT.
These venues will be abuzz with the continued growth of our ecosystem where we anticipate further CGT marketing approvals, in particular commercial TILs. Now that CRISPR-ed cells have met an inaugural marketing approval, this technological pathway is now wide open for a cascade of clinical use cases that offer promise for a wide range of monogenetic rare disorders and other broader reach applications. Continued clinical development of novel platforms including iPSCs for tissue replacement, CAR-NK and alternates, and the furtherance of marrying mRNA and cells will be hot items for the year to come.
Bambi Grilley (ISCT CRO – Chief Regulatory Officer) and Rachele Ciccocioppo (ISCT CSO – Chief Scientific Officer) are both focused on the patient’ perspective and access and she also like to remind me that marketing approval is simply the end of the beginning from the patient’ perspective. Patient access need be the end game and whilst this was all theoretical in past years, the large number of approvals in multiple jurisdictions now face the music of pricing and reimbursement. Set aside the hand wringing of who can or will pay for commercially viable CGT drug price, we’re now also observing in real world that independently of drug cost, patient out-of-pocket costs related to travel, housing, lost wages for caregivers especially for individuals who suffer from chronic housing, food and work vulnerability are substantial headwinds in patient hesitancy to take the cure – even if it was gratis. Indeed, these access concerns are informing substantial and possibly disruptive rethink by EMA in ’24 and other regulators who may try to emulate Japan’ PDMA attempts in making CGT approvals more facile and accessible on a risk assessment basis as well as more distributed access beyond urban centers.
However, the best remedy for patient access remains improved technology – and clear disruptive developments we can foresee arising in ’24 and beyond could include CAR technologies that forfeit lymphodepletion pre-conditioning, CARs without cytokine release syndrome (CRS) and off-the-shelf allogeneic CARs. Indeed, if there were to be allogeneic CARs that do not lead to CRS without need of toxic lymphodepletion, one could envisage that patients of modest means living far away from urban centers of excellence would more readily be amenable to accept therapies delivered through community oncology clinics without threat to their family finances. As we are now seeing allogeneic replacement cell therapies getting marketing approval and the inevitable approvals for iPSC products in this class, the next disruption will be designing immune evasive platforms that forfeit the requirement of long-term toxic immune suppression.
As always, open market competition in disruptive technologies derived from HI (Human Intelligence) may well best serve in forfeiting the predictable access limitations of first-generation CGT technologies and I say that we of the ISCT are going to be in the middle of it all – worldwide.
Jacques Galipeau, MD
President, ISCT
Associate Dean for Therapeutics Development
University of Wisconsin School of Medicine and Public Health
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