A BPI Theater Roundtable at the 2016 BIO Convention

On Tuesday, 7 June 2016, Mike Ward (global director of content at Informa) chaired an afternoon roundtable titled, “Challenges Associated with the Industrialization and Commercialization of Gene and Cell Therapies.” He brought together a panel of four experts:

• Morrie Ruffin (managing director, Alliance for Regenerative Medicine, ARM)
• Michael Werner (ARM’s executive director)
• Sarah Haecker Meeks (chief scientific officer, Adjuvant Partners; director of technology sections, ARM)
• Tom Novak (vice president of strategic partnerships, Cellular Dynamics International, a Fujifilm Company).

Discussion

The moderator posed several questions to his panelists. “Millions of dollars are being spent on [development of] these new therapies,” he prefaced.

What challenges has the industry overcome, and which remain: commercial, technological, or regulatory? What is different in 2016 than in 1996, when we saw companies spending millions of dollars to get into gene therapy? A number of things are different in terms of gene and cell therapies and tissue engineering. We have made much progress in safety, scalability, and commercialization. In terms of science, we know more about how to express and deliver genes now. One major improvement has come with pluripotent stem cells (adult cells that are genetically reprogrammed to an embryonic stem-cell–like state) for use in both drug discovery/testing and cell therapy applications. When embryonic stem cells were all that were available, their use was controversial and discouraged investors. In gene therapy, researchers started working with vectors, and academia studied them. Now enough work has been done to provide evidence that those vectors are safe and efficacious, moving them toward commercial development. Regulatory issues remain to be addressed, as do questions regarding market access and reimbursement.

What is the situation with tissue engineering by comparison? Tissues are typically scaffolds and cells. Now we can make a variety of cell types efficiently and economically. Combining those advancements in material science makes this an exciting area for investment. With a body of evidence showing how safe tissue engineering can be, regulatory agencies can approve such products with confidence.

Whether ethical or safety related, regulations are clearly important. How close are we resolving these concerns? Some of the basic issues have been resolved. More challenges will arise as the technologies become more complex. Meanwhile, patient groups want regulators to make it easier to get products approved and to market. It is a challenge to find the correct balance between accelerating therapies for patients and maintaining safety and oversight by regulatory agencies.

Has any authority in the world gotten it right at the moment? Some people think that Japan might have done so with its new law giving conditional approval to products that pass phase 1 safety (with plausible reason to believe that they will be efficacious). Companies still need to conduct detailed phase 3 studies and file for continual market approval after seven years. The country has three payers that legally must cover such therapies, so many companies are now showing interest in doing business in Japan.

Do you think that we will see regulatory agencies around the world harmonize regulations associated with emerging therapies? We will probably see more convergence than harmonization because of the different cultures and government systems. But the Food and Drug Administration (FDA), European Medicines Agency (EMA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) tend to cooperate and accept data from each other’s countries as evidence.

This biotechnology field is now mature enough that it can withstand a failure; 20 years ago, the whole gene therapy field stalled when negative results were reported. There haven’t been very large investments in emerging technologies yet, however, and companies still face challenges in raising money to proceed with development and trials.

What is the one action that you would like the policy makers to do to help? It would be good to have a set of standards to measure products against. There has been progress made toward developing standards and getting validation from the regulatory agencies. Many groups have been working on standards, but that has been a fragmented pursuit. We need an industry-wide agreement on standards.

What are the technical challenges? They are centered on industrializing the development process for emerging therapies by trying to optimize cost, yield, efficiency, and reproducibility. These problems will be easier to solve when standards and tests are in place. Technical issues are one part of the puzzle; the others are gaining payer acceptance and setting justifiable prices.

The panelists in turn asked Ward what he sees as the main challenges. He listed two main issues:

• How do you industrialize the whole process?
• What should come first: developing new products and then looking for a market, or determining whether a market exists first and then working out the manufacturing?

Ward also mentioned personalized medicine. Such technologies fit one person at a time rather than the “one size fits all” approach of blockbuster therapies. What may be needed is a universal cell — for example, chimeric-antigen receptor T (CAR-T) cells — or “super donors” whose cells could work for a group of people. Companies tend to be more interested in allogeneic therapies than in autologous products for which one manufacturing batch is for one person.

But it may be that one size no longer fits all in paying for biologicals, as well. A product could cost different amounts for different patients. Information technology that can follow each patient’s cells through engineering and back to them will be necessary.

Who will be delivering these needed technologies? “Big pharma” companies will deliver some emerging therapies, and new companies will develop to meet unmet needs. New forms of reimbursement will dictate corporate structure.

Companies must to be able to demonstrate expensive drugs’ value, especially if they claim to cure a disease (e.g., hepatitis C). They need to show that the cost of a cure is lower than the cost of ongoing treatments and hospitalizations.

Is there a “poster-child” disease or condition that will break through and demonstrate that kind of value? A cure for a rare fatal disease that affects children has already come out, and payers did pay for it. But the question remains whether payers would do so for a cure of a more common disease such as diabetes.

What are you optimistic about? Good clinical data is coming out for these technologies. We need to address pricing issues. They can work out — but might need a different system in place to do so.

Manufacturing is possible. Companies that have expertise in industrialization are beginning to be involved. The state of the science is good, and previously untreatable diseases will be treatable. Society will demand that we solve the other issues.

The ability to derive cells from stem cells has greatly improved our outlook. Government under President George W. Bush limited embryonic stem cells. But now pluripotent stem cells help companies and academics get around the conflicts of embryonic stem cells and find treatments for serious conditions using them. •

Alison Center is editorial assistant (acenter@bioprocessintl.com) for BioProcess International, PO Box 70, Dexter, OR 97431. Recordings of many of these full presentations are available online at www.bioprocessintl.com/BIO2016.