University of Wisconsin School of Medicine and Public Health
The commercialization landscape for Cell & Gene Therapies (CGTs) has benefitted from an unprecedented bull run with logarithmic growth in marketing approvals (MA) throughout diverse regulatory jurisdictions. This pace of growth for future MAs is anticipated to continue. A growing swarm of clinical-stage CGT startups - mostly, but not exclusively, developing immune effector cells for cancer therapy - have sprung up, chasing the unambiguous success of CAR T cells and analogous CGT platforms. A rising tide lifts all boats. The use case of living therapeutics for cancer as well as blood stem cell disorders (thalassemia major, sickle cell disease), autoimmune (diabetes mellitus, Systemic Lupus Erythematous) and regenerative applications (Parkinson’ disease, retinal disease, hemophilia) are now approved or within grasp. The confluence of decades of bench and clinical research output and marvelous clinical outcomes merged with access to easy capital to allow for this boomlet to emerge. Building on this momentum, there is much to rejoice about - from scientists in lab trenches toiling for the next great idea to entrepreneurial commercial developers actualizing the practicalities of MA and deploying these to patients.
True, the bears have entered the fray with marked tightening of capital in the past year, with the inevitable pullback anticipated for the more data light commercial launches. That said, the now established remarkable use case of CGTs will provide resilience to the ecosystem and continued opportunity for disruptive innovations bubbling up from scientific inquiry into next generation living therapies that are more broadly applicable (allogeneic), safer (avoiding toxicities like cytokine release syndrome), and accessible (lesser cost-of-goods and better risk-adapted regulatory pathways for MA).
Only when you have achieved an unambiguous measure of pharmaceutical development success do Benjamins come into play. Distinct from all prior classes of drugs, including medicinal chemistry and biologics, CGTs offer the possibility of “one and done” life-long curative interventions, akin to allogeneic bone marrow transplant for primary immune deficiencies. In addition to improved patient quality of life, a “one and done” may also offer substantial healthcare cost avoidance over the lifetime of cured patients. The latter variable informs a meritorious narrative for “fair pricing” that commercial developers integrate in their pricing strategy. Hence, recently approved first-in-class CGTs are creating the precedent of a course of treatment readily exceeding the multimillion-dollar mark per patient. The business thesis for pricing of curative “one and done” are the object of a Financial Times editorial in which ISCT President-Elect Miguel Forte is quoted. The authors foreshadow public payor challenges on the horizon for expanded applications of CGT for more prevalent indications such as sickle cell disease, even in wealthy national jurisdictions such as USA. A conclusion drawn is: “From a patient access and advocacy perspective, if there were delays in access from a payer constrained side, that would be a PR nightmare. I think it would harm people but it would also be very bad optics for the payer.” Payors, especially publicly funded healthcare systems seek “value pricing” in the goal of improving patient outcomes and cost containment. Economic diplomacy between interested parties should be entertained to bridge expectations between fair pricing and value pricing.
In parallel, publicly funded CGT manufacturing capacity embedded within National Government payor healthcare systems in the EU are now being leveraged to deploy CGTs to their citizenry, as exemplified by the Netherlands initiative to fund locally-manufactured TILs for metastatic melanoma and EMAs launching of a new Spanish pilot program to help academic and other nonprofit researchers developing advanced therapy medicinal products like CAR-T. Considering the substantial CGT GMP-compliant manufacturing capacity in EU publicly-funded healthcare systems, it is safe to predict that more national entities with government-funded healthcare systems will follow the Dutch & Spanish precedents. However, harmonized regulatory approval policies throughout the EU may need to be adapted to accommodate these emerging CGT deployment strategies by member States.
Free market forces remain the best driver for useful technologies, including CGTs, to emerge and be deployed for mass use. Commercial developers must have the opportunity to thrive in the national economy’s best interest. The participation of publicly funded healthcare systems in the fray creates novel partnering opportunities for finding (1) creative, fairly valued pricing for developers as well as (2) beneficence through improved quality of life for patients and cost avoidance for society.
The strength of ISCT is that we are the only global society where the interested parties - publicly funded academia, private and public CGT manufacturing, regulators, ethicists, and commercial developers - all sit at the same table to come up with sustainable solutions for deployment of the living therapeutics we care so deeply about.
Therefore, at the ISCT Paris Annual Meeting, you must attend to take part in this important conversation.
 JAMA Pediatr. 2021 Jun 1;175(6):617-623. doi: 10.1001/jamapediatrics.2020.7140.