Nearly a year ago, the International Society for Cell Therapies (ISCT) decided to integrate industry into its organization to build a stronger platform for commercializing therapies. Robert Deans, vice president of regenerative medicine at Athersys, was invited to serve as a leader of ISCT’s Industry Task Force, which aimed to identify industry roles in its organization. Within two months, the task force invited industry members and chartered a white paper (1) that described how ISCT should go forward. As a result, its Commercialization committee was formed.
Deans currently serves as Commercialization committee chair, with co-chairs Richard Maziarz (Oregon Health and Science University) and Francesco Lanza (Hospital of Cremona, Italy). This committee aims to set specific benchmark objectives for the relationship among industry, academia, regulators, and ISCT members this year. Along with ISCT, it is also committed to forming an “Industry Community,” an advisory panel of industry representatives. These two organizational units are set up to foster industry’s role in commercializing cell therapies. The committee is further organized into four subcommittees, one of which is Clinical Development and New Product Introduction, chaired by Deans. During a BPI interview, he described the objectives of both and provided his view on key questions.
BPI: What are the goals of the Clinical Development and New Product Introduction subcommittee?
RD: “We focus on bringing global regulatory agencies together with key translational medicine opinion leaders in academia and industry. In workshops and focus groups, these experts are tasked with identifying commercialization hurdles in specific therapeutic areas. These efforts include identifying or setting standards for cell characterization so that investigators can distinguish among competing or alternative cell therapy products. They also include evaluating current clinical trials and clinical endpoints in trial designs so that people can share lessons learned from existing studies. The subcommittee makes recommendations to regulatory agencies on standardized preclinical models and clinical endpoints that are best suited to evaluate the effectiveness of cell therapy in these new trials. And, most important, we provide pharmaceutical companies and healthcare companies with a “risk measurement” for entry into this therapeutic space.
BPI: What is needed to standardize preclinical models and safety assessments in certain disease areas?
RD: It involves committing to an animal model with standardized surgical or other procedures for inducing disease; setting standards for the number of animals in groups and the types of controls that should be run; and setting standards for establishing a dose response in a cell therapeutic so that you get a valid interpretation of potency of a cell population.
For example, probably three to six groups are using adherent stem cells like mesenchymal stem cells (MSC) for treating stroke — these are just coming into the clinic. There are many different rodent models, both mouse and rat, available for testing cells for their efficacy in treating stroke, and they differ by degree of damage and by type of behavioral readout that is observed.
Investigators differ in how they analyze tissue for safety or for physiological improvement. So one task for ISCT through the new products subcommittee meetings is getting regulatory agencies to meet academic thought leaders and industry participants who are filings investigational new drug applications (INDs) to proceed clinically. The subcommittee wants them to debate and agree on the most effective animal model to show a certain property. This will encourage the FDA to start to mandate a consistent standard in testing a certain disease state, and both academia and industry will be aware in advance of expectations. As a result, they can streamline their development process.
BPI: How would you describe current developments of cell therapies?
RD: Many new exciting cell therapies have come forward and are now entering either phase 2 or phase 3 pivotal commercialization trials. Many of these are driven by biotechnology companies that have limited capital and are focused on showing proof of mechanism for — in principle — the effectiveness of a therapy. But they lack the capital to go through a pivotal approval trial, which is a late-stage, very large clinical trial. Because cell therapeutics have so many properties in manufacturing and in function that are different from drugs or biologics, the pharmaceutical industry and the healthcare industry have been averse to investing in these late-stage trials.
ISCT and the Commercialization committee are trying to present a scientific perspective and a regulatory perspective to reduce the risk and encourage investment. That is probably one of the key endeavors of the clinical development subcommittee: to adopt an open-code development philosophy. We are encouraging industry members and academics to make their trial design and their trial data open for all to share, and then use that to foster and educate big pharma so that we can reduce their risk to invest in these trials. We’re really trying to stimulate both intellectual investment and financial investment in later stage cell therapy.
BPI: How is the committee conducting the necessary risk analysis?
RD: We hold forums of 20–50 participants who debate around those topics. We structure a point– counterpoint type analysis and publish the outcome in the appropriate therapeutic society journal. Before bringing this concept into ISCT, this is something that we have been involved with in the areas of stroke and solid-organ transplant. It has been quite successful.
BPI: Would you consider regulatory issues in your list of potential roadblocks or necessary areas of understanding?
RD: Yes we would, particularly with heterogeneity in the global regulatory environment. It is very important to understand the regulatory environment in different geographies so that you can optimize your patient accrual and trial design accordingly. An extension to this relates to understanding regional differences in standard of care. Healthcare management prior to and following treatment is a significant variable in outcome determination and may confound clinical interpretations in a global study. ISCT aims to bring these issues forward as part of their global initiative for commercialization.
BPI: What are some of the misconceptions about cell therapies?
RD: There is still confusion in the lay public between embryonic stem cells and adult cell therapies. So it is important to continue to educate about cell strategies currently available. There is also a big gap in knowledge around development cost and product cost for a cell therapy, and a very big gap in anticipating the reimbursement likelihood for some of these emerging therapies. Industry doesn’t know how much the reimbursers — the insurance companies and the medical providers — are willing to pay for certain therapies. And they are also not clear o
n what it is truly going to cost in terms of a manufacturing platform to produce these therapies. That is a very important aspect of cross-education and trying to bring issues into an open forum.
BPI: What is needed to for an efficient manufacturing process?
RD: There is still quite a way to go, both in the context of autologous cell therapies and allogeneic cell therapies. With autologous therapies, in part, it’s the cost of production. A major expense is individualized production hardware and lot release testing. In allogeneic cell therapy you can generate many clinical products from one manufacturing run. The same cost for lot-release testing is averaged out over all of the products, so your overall costs decrease significantly. That is one of the biggest issues for the business model discrepancies between autologous and allogeneic cell therapies.
BPI: What is the Commercialization committee working on right now?
RD: We just finished our first workshop on cell therapy in peripheral vascular disease (mid-January) with a cardiovascular conference in New York City. We had about 10 industry representatives present and about an equal number of key opinion leaders as well. Our next workshop is going to be on allogeneic bone marrow transplant and managing graft-versus-host disease. We have a venue but have not made a public announcement for this focus group yet. The event we are having after that is on the use of biomaterials in solid organ transplantation, to be held at the ISCT annual meeting in Rotterdam. Our fourth workshop is planned to focus on inflammatory bowel disease, which is scheduled to be held in June 2011. All of these have a balance of academic thought leaders, regulatory agency representatives, and industry participation.”
Maribel Rios is managing editor of BioProcess International, 1-646-957-8884, firstname.lastname@example.org.