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  • Martin McGlynn

Curative Medicine: Here We Are... Ready or Not!

There is a world of difference between medicines that treat the symptoms of a disease, those that have the potential to alter the course of a disease, and now those that actually offer the prospect of a CURE. Not only would curative medicines dramatically alter the lives of patients and their families, as well as the practice of medicine itself, but they would bring with them many challenges for society to address beyond considerations of cost and patient access. They would force us to confront a raft of social, ethical and political considerations, particularly as curative therapies expand beyond their current, very limited focus on rare, mostly genetic conditions.


The Mission of the Center for Definitive and Curative Medicine (CDCM) at Stanford is to cure children and adults with currently incurable diseases through the development of innovative cell- and gene-based therapies.

I was invited to attend the 2nd Annual CDCM Symposium held on February 27, 2018 on the Stanford Campus. I am pleased to report that under the leadership of its dynamic Director, Dr. Maria Grazia Roncarolo, CDCM is already well and truly on the way to fulfilling its mission! Dr. Roncarolo and her colleagues at CDCM have created what appears to be a seamless infrastructure and operating and financing systems to marshal the different medical fields including Oncology, Immunology, Cardiology, Dermatology, Hematology, Neurology and many others, in order to efficiently translate discovery research conducted at Stanford into the clinic and ultimately into viable curative therapies. They have also managed to recruit the Office of Clinical Trials, the Laboratory for Cell and Gene Medicine and the Office of Technology Licensing to join the cause — no mean feat!


CDCM already has INDs in progress for T-depleted Stem Cell Transplantation (PI: Judy Shizuru), Autologous Skin Grafts for Epidermolysis Bullosa (PI: Jean Tang) and Induced Alloantigen-specific T-Regs for GVHD Prevention (PI: Maria Grazia Roncarolo). In addition, the Center has a Pre-IND program under way for Sickle Cell Disease (PI: Matt Porteus), using CRISPR technology to gene-correct hematopoietic stem cells. They have a long way to go to bring these very promising technologies into clinical practice, but they are in the pipeline, right now.


Invited guest speakers included Michel Sadelein, MD, PhD, who is Director of the Center for Cell Engineering at Memorial Sloan Kettering Cancer Center and Scientific Co-Founder of Juno Therapeutics, soon to be acquired by Celgene for $9 billion. His group was the first to publish dramatic molecular remissions in patients with chemo-refractory acute lymphoblastic leukemia (ALL) following treatment with CD 19 CAR T cells, “which offers the prospect of complete remissions in patients with chemo-refractory/relapsed B cell malignancies, especially ALL.” Interestingly, Dr. Sadelein pointed out that there are some 240 CAR T cell trials registered on the U.S. National Health Institute’s clinicaltrials.gov, approximately 80 CAR targets being investigated in preclinical studies and over 40 Biotech companies with an active CAR program!


One other statistic that made me sit up and pay attention: More than 50% of CD19 CAR therapy trials underway are in CHINA. One audience member worried about the potential for bad outcomes from insufficiently regulated trials in jurisdictions such as China, and the potential that might have to set the whole field back.


A second guest speaker, Kathy High, MD, co-founder, President and CSO of Spark Therapeutics, treated us to a very informative presentation of Spark's journey to bring LUXTURNA to market. Last year, the FDA approved LUXTURNA, an AAV vector-based gene therapy, as a treatment for an autosomal recessive form of blindness, and it is currently under review by the EMA. It is now one of three gene therapies approved for genetic disease, the other two being Glybera for Lipoprotein Lipase Deficiency, approved by the EMA in 2012 and Strimvelis, approved by the EMA in 2016 for ADA-SCID.


The high cost of the therapy ($850,000) is challenging the entire Healthcare system, and presents some first-of-a-kind challenges never before experienced with a newly approved treatment. For its part, Spark is working diligently to come up with creative payment and distribution options to support patient access to LUXTURNA, one of which offers a "money back guarantee" in the form of outcomes-based rebate arrangements. The company reports that it is still in discussions with the U.S. Centers for Medicare and Medicaid Services (CMS) regarding possible installment payment mechanisms.