Cell and gene therapy is, at the risk of sounding trite, at an inflection point. The number of cell therapies in clinical trials has grown 21 percent since 2015, with more than 759 trials underway globally. With that growth and passage of the 21st Century Cures Act, “we have to be serious about large-scale commercial production,” according to Robert Preti, chairman of the Alliance for Regenerative Medicine, speaking at Biotech Showcase™ 2017. That requires addressing challenges in manufacturing and reimbursement.
Part of the issue is that regenerative medicine is new and highly personalized. Consequently, there are no industry standards to guide scale-up. It also lacks quantities of data showing the real-world, long-term efficacy that payers expect.
Discuss reimbursement early
The reimbursement issue should be driven not by what you can charge but by what you should charge, according to Jeff Walsh, chief financial and strategy officer, bluebird bio. He recommends starting discussions with payers very early—as soon as the products enter human trials. “Coming in during late-stage trials with a very high price makes discussions fraught with animosity,” he points out. Instead, “we have a unique opportunity to engage with payers that can become transformative during the next few decades.”
Pay for performance is likely to figure strongly in those discussions. For example, Manfred Rüdinger, CEO, Ciadis Pharma, approaches payers with a holistic argument. For discussions, he compiles data regarding the overall survival rates, days spent in intensive care, days before discharge, average number of episodes and similar metrics for the standard of care and for the drug he is advancing. Such complete data makes a compelling case for reimbursement based on reduced costs and improved quality of life—and, therefore, productivity—for the life of the patient.
Exactly how reimbursement will be structured remains a question, even without the likely changes in the US healthcare system.
Scale-up is a particular issue
Before commercialization, however, “manufacturing is the sticking point,” Chris Mason, CSO, AvroBio, emphasizes. Working closely with regulators early in the process to find creative solutions overcomes some of the issues.
Manfred Ruediger, CEO, Kiadis Pharma
Many of the manufacturing challenges can be solved by implementing closed processes and automating as much as possible, Rüdinger adds. Processing in a closed system, from cell extraction to reintroduction, allows allogenic products to be processed in a single clean room and often a lower-level clean room, which lowers costs.
Related challenges include:
- Because regulators and developers both are feeling their way forward regarding cell therapies, choosing the wrong metrics can slow development. Involve regulators early, as if they were consultants, to ensure trials are designed and specific results are evaluated in ways that make sense to both parties.
- The infrastructure for Amazon-like delivery currently is lacking. But, given the low number of commercialized products, it is surmountable.
- Quality professionals. Professionals trained in quality measures are in high demand. Companies with outstanding quality systems and those that take the extra steps to create true centers of manufacturing excellence will have a significant competitive advantage.
Having the right facilities can be another challenge, particularly for small firms. Matthew Patterson, president and CEO of Audentes Therapeutics, renovated a warehouse to produce the needed materials when his therapeutic was still in the preclinical stage. “It was scary, but not terrifying,” he says. Now Audentes has two 500-liter bioreactors making GMP material and “we are thrilled with our choice.” The company continues to add analytical tools in-house to characterize products and support rapid scale-up.
Will results match expectations?
The genomic breakthroughs of the past 20 years have contributed to a widespread belief among patients and some investors that gene therapy will be a panacea once therapeutics are widely available. They may be right. Breakthrough therapies are entering the market and more are just on the horizon. At the same time, assays are becoming more sensitive, and the bioinformatics project to understand populations is extremely exciting. The tools are evolving to address complex diseases.
As the industry advances products into clinical trials, ultimate commercialization is being affected. “Patients must get these therapies, so we must build development plans that set us up for success, to evaluate the burden of disease, to engage with stakeholders early,” Patterson says. “There is no one-size-fits-all approach (to business and reimbursement models). We need a range of options to ensure that each product developed can reach patients.”