Jacques Galipeau, MD FRCP(C)
President, ISCT
Don and Marilyn Anderson Professor in Oncology
Associate Dean for Therapeutics Development
University of Wisconsin School of Medicine and Public Health
The cure of Emily Whitehead’s leukemia with her own gene engineered lymphocytes in 2012[i] will certainly be recognized by posterity as the watershed moment that launched the modern era of cancer cell immunotherapy – and this rising tide of inarguable success is lifting all the boats in the Cell and Gene Therapy (CGT) space. The recently FDA approved one-and-done CGT cures adds to the goldrush febrility of the field writ large as well. Indeed, a quick google search reveals an ever-expanding swarm of clinical-stage commercial ventures in the CGT industrial ecosystem risking effort, sweat and capital in developing the next disruptive innovation addressing rare and common ailments with unmet medical needs. The explosive rate of CGT marketing approvals (MA) worldwide speaks to a Rubicon crossed where CGTs are here to stay. Having won the battle of clinical relevance, the CGT space needs to win the war of sustainable deployment.
I’d propose that like all innovations in products and services, we can look to other industries to provide guidance on how best to capitalize our aggregate success. At its infancy, commercial air travel was a luxury item afforded by few. Technical innovations such as the jumbo jet allowed for extended and expanded services by select big-name airlines, yet headwinds to affordable access remained. However, the revolution in democratization of air travel in US arose from the 1978 deregulation act[ii] that dramatically increased competition without compromising safety. Joe and Jane could now fly to Florida from Vermont rather than drive, for comparable costs.
Akin to the evolution of the air travel industry, patient access to emerging CGTs that improve Quality Adjusted Life Years (QALY)[iii] and at times lead to cures would also be well served by the Darwinian forces of the open market driven by competition fueled by innovations from the best minds in academia and industry. That said, the unique nature of personalized, bespoke living therapeutics – especially for rare or underserved disorders - are associated with discovery and development costing schemes that are radically distinct from yesteryear’s medicinal chemistry model. A reflection on paths to marketing approval pathways to include risk-adapted CGT conditional approval schemes à la PMDA (Pharmaceuticals and Medical Devices Agency) in Japan[iv] and leveraging of publicly funded CGT manufacturing infrastructure within healthcare systems à la TerCel[v] in Spain[vi] need to be examined as plausible complements to the current status quo. Akin to the airline industry, the modernization of regulatory pathways to CGT marketing approval whilst unsparing in safety oversight is possible, even necessary, in most international regulatory jurisdictions to ensure equitable access.
Notice be given, the conversation regarding sustainable commercial success of approved CGTs now needs to also include post marketing approval key stakeholders: Patients, Providers and Payors (PPP). Although we believe our CGT cures will be inarguably adopted by patients, it is always sobering to learn about their perspective that goes beyond living with illness and informs their willingness to receive treatment[vii]. We must also walk in the shoes of healthcare providers that at bedside may be unwilling to fulsomely promise a mom that her son will indeed be cured for life by a novel CGT without any long-term risk. Physicians toil within healthcare systems that must contend with razor thin operating margins at risk of erosion due to byzantine cost recovery schemes for pricey CGTs as well as being addled by onerous and duplicative industrial administrative post marketing compliances[viii]. Lastly, payors – both public and private insurance programs – may simply exclude approved CGTs out of their plans unless there is unambiguous value pricing and societal benefits.
That said, CGTs are here to stay. They can cure ill children from crippling disease, they can provide cancer remission for previously terminal disease, and we can envisage applications mending a wide array of acute and chronic illnesses. Disruptive innovation through science, the forces of open market competition facilitated by modernized risk-adapted approval schemes and attention given to the aspirations and perspective of Patients, Providers and Payors are all ingredients in the on-going success and societal impact of our field.
Looking forward to seeing you all in ISCT 2023 Paris to discuss over a café au lait or apéro…