Guest Commentary: From Prop. 71 to CAR-T and beyond: Enabling another 15 years of patient-centric innovation

From Prop. 71 to CAR-T and beyond: Enabling another 15 years of patient-centric innovation

 

By Amy DuRoss

 

On a recent summer weekend, dedicated political and scientific leaders gathered in the Sierras to discuss paths to progress for our country. Amid the talk of major upcoming elections, addressing climate change, burgeoning trade wars, and growing educational gaps, another topic clearly stood out -- regenerative medicine. As highlights from more than 70 exciting new stem cell research studies were shared, I was reminded of another election cycle 15 years ago, and how far we’ve come.

 

In 2004, California voters passed the $3 billion California Stem Cell Research and Cures Act (Proposition 71) to help create a secure foundation for regenerative medicine in the United States at a time when federal funding support severely declined. No one could have predicted the myriad scientific and medical innovations that have arisen since, or the way our healthcare systems are pivoting to meet them. From an ongoing body of work in stem cell science to approved cell and gene therapeutics for late-stage cancer and rare genetic disorders, regenerative medicine is thriving today.

 

More than $37 billion dollars has been invested in the field since 2015 alone, according to the Alliance for Regenerative Medicine (ARM). There are more than 1,060 clinical trials in regenerative medicine underway worldwide, and almost 100 drug products have received some form of expedited approval designation. And in the meantime, a new digital infrastructure is being laid to deliver these new treatments to patients world-wide, safely and efficiently.

 

When we envisioned Proposition 71, we were most focused on stem cell research. But the field of regenerative medicine has since expanded. The original definition -- restoring or reestablishing normal physiological function by regenerating or replacing human cells, tissues, or organs -- has been broadened by new discoveries in science. With the advent of genomic engineering, the term has also come to mean re-engineering cells to circumvent biological mechanisms that make diseased cells look normal. Two approved cell therapies for blood cancer have recently brought this new capability into public view, by offering remarkable mechanisms to re-engineer the body’s own immune cells and turn them into powerful cancer killers.

 

Here’s a short timeline of some of the major developments in regenerative medicine:

Today, the innovations are coming at a pace so rapid that new headlines pop up almost daily. Gene therapies for inherited disorders such as childhood blindness, thalassemia, and spinal muscular atrophy have been approved by regulators. Vector-mediated gene therapies, delivered into cells by mechanisms such as viruses, have become so numerous that discussions of viral vector shortages and how to address them have become commonplace. The approved CAR-T approaches for blood cancers, based on re-engineering of immune cells known as chimeric antigen receptor T-cells, are being optimized to shorten manufacturing times and reduce side effects. Researchers are investigating how best to address solid tumors, utilizing other immune system-based mechanisms such as TIL (tumor infiltrating lymphocytes) and NK (natural killer) cells. Personalized cancer vaccines -- based on patient data and/or cells -- are also demonstrating promise against some solid malignancies. Multiple lines of inquiry are studying the potential therapeutic benefits of gene editing -- using technologies such as ZFNs (zinc finger nucleases), TALENs (transcription activator-like effector nucleases), and CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats) -- while regenerative medicine leaders work to keep use of gene editing technology safe and ethical. And combination therapies, either among regenerative approaches or between advanced and traditional therapies, are actively under investigation.

 

In the meantime, an entire infrastructure is being laid to support a new medical landscape that is truly regenerative and patient-specific. New digital technologies are enabling the safe, efficient delivery of personalized therapeutics, making sure that the right drug product reaches the right patient and enabling worldwide scale. In the first such requirement of its kind, regulators are now mandating that these enabling technologies are in place as part of approval review, ensuring a new digital safety net for patients in the regenerative medicine age. FDA leaders, who have demonstrated true leadership in this area, have stated they expect to receive about 200 cell and gene therapy IND (investigational new drug) applications per year, and are planning on approximately 10 to 20 annual approvals by 2025.[6] Major medical associations have taken notice of the field’s growth, with the American Society of Clinical Oncology named CAR-T cell immunotherapy its Advance Of The Year in 2018.[7] And payers and lawmakers have taken notice, with the U.S. Centers for Medicare & Medicaid Services (CMS) finalizing the decision to cover CAR-T cell therapy this year.[8]

 

Amid so much astounding progress, so much more work remains to be done. In a regenerative medicine world where the patient truly is the product -- where patients are an essential cornerstone of the cure -- here are four key advances that will help us reach as many patients as possible as quickly as possible.

Fifteen years ago, I joined with colleagues to help plug an important funding gap for  stem cell research. It is with deepest gratitude to those teammates and voters in 2004 that I look at the remarkable progress all around us now and envision where regenerative medicine will advance in the next 15 years. As was the case in 2004, not all of tomorrow’s advances can be predicted today. But I am more confident than ever that, by working together and committing true support to this field in a clear and focused way, we can create a broad personalized ecosystem. Today, in cancer and rare disease care centers, some patients truly are already the cure, receiving regenerative therapies that are transforming their lives. Let’s work together in earnest -- committing our innovations, effort, and resources -- to extend that opportunity to all patients in need.

 

1. C. Mason, P. Dunnill. (2008).A brief definition of regenerative medicine. Regen Med, 3(1):1-5.

2. G. Prindull, B. Prindull, N. Meulen. (1978). Haematopoietic stem cells (CFUc) in human cord blood. Acta Paediatr Scand. 67(4):413-416.

3. M.J. Evans, M.H. Kaufman. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature. 292(5819):154-156.

4. J.A. Thomson, et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science. 282(5391):1145-1147.

5. J. Liao, et al. (2015). Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Nat Genet.47:469–478.

6. Statement from FDA Commissioner Scott Gottlieb, M.D. and Peter Marks, M.D., Ph.D., Director of the Center for Biologics Evaluation and Research on new policies to advance development of safe and effective cell and gene therapies

7. American Society of Clinical Oncology. (2018.) CAR T-Cell Immunotherapy Named Advance of the Year in Annual ASCO Report.

8. Centers for Medicare and Medicaid Services. (2019.) Decision Memo for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers (CAG-00451N)

9. J. Kaiser. (2019.) NIH gets $2 billion boost in final 2019 spending bill

10. National Cancer Institute. (2019.) NCI Budget and Appropriations

11. U.S. Food and Drug Administration. (2019.) FY 2019 FDA Operating Plan Narrative