Advocating an Evolution

In a 2006 report, the US Department of Health and Human Services hailed regenerative medicine as “the vanguard of 21st century healthcare” and “the first truly interdisciplinary field that utilizes and brings together nearly every field in science” (1). To fuel support for regulatory, legislative, and reimbursement initiatives in this new therapeutic class, a small group of scientists, life science business executives, patient advocates, and other experts formed the Alliance for Regenerative Medicine (ARM, http://alliancerm.org). Starting with 17 charter members, the organization now includes more than 130 participants. Here, I discuss ARM’s objectives and current projects with cofounder and executive director Michael Werner and managing director Morrie Ruffin.

Objectives and Organization

BPI: What are ARM’s primary objectives? How does it differ from other groups?

Ruffin: ARM was formed in September 2009 as the first organization in the regenerative medicine space to focus on the clinical advancement and commercialization of regenerative medicine technologies and therapies. We did this at the urging of a number of key people in the field, many of whom are still in the sector.

Michael is a lobbyist and worked with me when we were both at BIO [the Biotechnology Industry Organization] in the mid-1990s. He was really the first stem cell lobbyist working for the sector. The recognition on both of our parts was

that the sector needed this type of dedicated effort if it was going to operate more effectively in Washington within the policy community, before regulators and key decision-makers, and in the reimbursement world. We had a number of conversations with some key stakeholders, including stem cell and cell therapy companies, investors, academic research institutions and big pharma companies that were then and are still engaged in this space such as Johnson &Johnson and Pfizer. We now have many more companies involved with us, including manufacturing and service companies such as Lonza and equipment companies such as EMD Millipore. Patient advocacy groups are also very active members of the organization.

ARM is not a trade group or trade association but rather a multi-stakeholder advocacy coalition promoting clinical development and commercialization of advanced biotherapeutics. We are organized into eight committees ranging from regulatory and reimbursement, to science and technology, and capital formation. We believe that this model of focused advocacy is the most effective way to operate in Washington today. Policymakers are more interested in hearing from a sector that is represented by a variety of different perspectives, and that is what we set out to do in bringing this group together under the umbrella of the alliance. It’s a very vital and active organization. We are still growing at a significant rate, and there is a lot of enthusiasm for our work right now.

BPI: How does ARM’s growth reflect that of the industry and what is happening in regenerative medicine?

Ruffin: There is real momentum in this sector; we are witnessing it in everything we are doing right now. Michael and I just came back from the JP Morgan meeting in San Francisco, where we had a number of activities going on. We conducted a day-long strategic planning meeting there involving our leadership and other experts in the field — each year it becomes a bigger group. We also held our third annual state-of-the-industry briefing, which is also attracting a larger audience each year. We are busting at the seams now with a lot of interest in the sector. We see it in the media, from big pharma because of how much they are involved in what we are doing, and now we see it from investors.

Regulatory Projects

BPI: What can you tell us about ARM’s efforts in regulatory initiatives?

Werner: As Morrie said, one of the factors that distinguishes us is that we are a multi-stakeholder organization. The other is that we are focused on commercialization issues; andaddressing regulatory issues are critical to successful commercialization. If you talk to experts working in regenerative medicine and at the FDA and ask them what is needed to get those products to market, one of the answers that comes across is a clear and predictable regulatory pathway. That is the objective of our regulatory agenda: a clear, predictable pathway to market for regenerative medicine products.

We decided that from the beginning we were going to work collaboratively with the FDA on that objective. We are not going to see the agency as our enemy or as an obstacle. The FDA wants what ARM wants: to make sure that safe and effective products get to patients as soon as possible. So we were going to work together to identify the barriers to that and work together to try to resolve them.

So since its inception, ARM has had good interactions with the FDA. We have a robust regulatory agenda in which we have published a paper about best practices for industry regarding working with the agency on cell therapies (2)— everything from the best way to communicate to how to approach your end-of-phase 2 meeting. It’s specific and technical, but it’s also incredibly useful for companies that are trying to get their products approved.

We also have had conversations with technical and scientific experts about cell potency assay development and validation. We’ve presented at FDA public meetings and have talked to the agency about PDUFA [Prescription Drug User Fee Act] and FDASIA [Food and Drug Administration Safety and Innovation Act] implementation. For example, we participated in FDA discussions about risk–benefit models. In those talks, we made sure that when the agency is deciding on criteria to use when picking indications, it takes into account unmet medical needs and the importance of patient involvement. Many indications that we discussed are those for which regenerative medicine is a possible treatment. So, our work with the agency is ongoing and detailed.

We are also working on issues in international regulatory harmonization. It has almost become cliché to say that companies respond globally and that the regenerative medicine field is a global one. How companies are regulated in Europe and the United States is important. So too is it important to make sure that there are consistent standards and consistent rules and definitions. ARM was approached by the FDA and the EMA to work collaboratively on such issues. So at the BIO-Europe meeting in Barcelona this year, we will have a session about that. We are also holding a workshop later this year with the FDA and the EMA on those topics. ARM is working on the key obstacles to getting products on the market

BPI: Are there models you can follow when decidi
ng on the key issues for regulation?

Werner: Which issues in other models are similar to those for regenerative medicine and which are not? That is a key question for both regulatory and reimbursement spaces. For some biologics, the FDA has a well-established process about how to file for market approval. For example, the agency has rules about when a product needs a BLA [biologics license application] to get to market and when a cellular product does not. But the question is whether any of those processes for biologics need to be tweaked for regenerative medicine, or is the basic framework okay? Another example we’re addressing is the need for appropriate animal models and pre-clinical standards for cell therapy products. We’re examining FDA’s treatment of these issues and whether changes are needed. We will be developing a white paper on this topic to present to FDA.

When we are trying to implement very specific regulatory policies, are there particular issues for this sector? That’s when you get into issues such as standards for cell potency assay development. For a biologics evaluation, you have to demonstrate potency of a cell and do lot-to-lot testing. But in a regenerative medicine context, how do you develop an assay that will sufficiently demonstrate the important information for FDA? That’s how we approach it: we don’t need to have a whole new pathway; rather, we ask ourselves, “What are the particular issues with those products, and how do we apply them in the context of FDA’s regulations?” We are not asking the agency to draft a whole new set of regulations. Rather, we are talking to them about reviewing existing regulations and determining what is new about regenerative medicine technologies that requires a new look at them from a different perspective.

Assay Development Projects

BPI: What are some specific examples of ARM’s work in cell potency assay development and validation?

Ruffin: ARM’s Science and Technology committee has several working groups that are in the process of drafting white papers about some of the topics Michael mentioned. Our work began with trying to understand potency assay development best practices as well as the ability to develop reference standards for use in the development of such assays. That work has morphed into a series of papers that are much more specific to other types of assays — some of them being precursors to potency assays.

We have one group that is working on cell count and viability assays, another working on purity and identity assays, and one each working on angiogenesis and immune modulation assays. Most are near completion in terms of their first draft and will then undergo peer review. Our hope is that in the first quarter of this year, we will be in a position to publish them, either first quarter or early second quarter.

A new initiative of the Science and Technology committee this year will be to survey big pharma companies to gain a better understanding of their current perception of the regenerative medicine sector, especially in terms of scientific and technical challenges. There are a lot of discussions about the use of stem cells in drug discovery, but a number of companies obviously are also interested in therapeutic applications. One of the things that we are going to be doing over the course of this coming year is to really try to understand — through a series ofinterviews — the perspectives of large and midsize pharmaceutical and large-cap biotechnology companies.

We have a group that is just coming together to start a data collection activity as part of the work needed for our annual report. ARM is in the process of broadening the amount of information collected on the sector and expanding that work for our next report, which we expect to be released in April. The report will include economic data and information about deals and transactions, money raised, how the sector is performing, and current clinical trials. It will be a very comprehensive overview of where we are in the clinic in most of the major disease categories. We expect the report to be done in time for our first New York investor meeting scheduled for 17 April. This will be the first regenerative medicine–focused investor event held in the United States.

Education Projects

BPI: How does ARM ensure that patients and other groups understand regenerative medicine? Are there challenges in addressing misconceptions?

Werner: People are still learning what regenerative medicine is. A big part of what we do — the corollary to our work in commercialization — is education. Morrie talked about educating investors and regulators, but ARM also has to educate Congress and the media about the facts of regenerative medicine. Regenerative medicine products are already on the market, and products in late-stage clinical trials hold great potential. We see education as the other role of the Alliance. We have access to information, and we have the capability of educating other groups. As far as education needs, we have run the gamut. We’ve heard from people who admit they don’t know what regenerative medicine is to those who think that, for example, embryonic stem cells are regenerative medicine.

So we face challenges sometimes when we get into those kinds of misperceptions — exactly what the technology is, how far along it is, and the fact that there is nothing controversial about it. Regenerative medicine is a technology that has been demonstrated through products that are already on the market, and it can yield tangible benefits for patients in very cost-effective ways. There are lots of late-stage clinical trials that are targeting unmet medical needs. Once people learn about it and see all of that information, then they understand why it is critically important technology.

Like many new technologies, especially those that didn’t have anything like the Alliance to push it forward during the years, there is definitely an education process that has to happen. The points in a 2006 article from the Department of Health and Human Services (1) are big parts of our legislative campaign: trying to get regenerative medicine products not only acknowledged, but launched. What is very interesting about it is that it was written by people at the FDA and NIH [National Institutes of Health]. So the people who have learned about the technology understood its benefits. Our task now is to broaden that understanding. Once we do that, then perception problems go away.

Projections

BPI: What are your predictions about where the industry is heading? (Note: responses are personal opinions, not necessarily the positions of ARM or any other organization or company.)

Werner: I think that big pharmaceutical companies will continue to embrace regenerative medicine technologies — even more than they have — over the next five years or so. As more clinical data demonstrate the power of this biology, more big pharmaceutical companies are going to embrace it, adopt it, and push it forward with commercialization strategies, which will lead to even more investments on the private side. My predication is that over the next five to 10 years, we are going to see a lot of clinical success in this space and products getting to the market and helping patients in ways that few people today would anticipate.

Ruffin: I think we are already beginning to see this. For example, Shire has announced that regenerative medicine is one of the three pillars of its future strategy. We are already seeing similar actions in other companies. I agree with Michael that in many ways the drivers will be data and clinical results. There are a number of major clinical events that we can look forward to over the next couple of years as these new products make their way through the clinic. As soon as we see a couple of additional products on the market, it will lead to renewed interest in regenerative medi
cine and provide some real momentum — especially if those products really do meet the expectations of the clinical community. We are already seeing great anticipation, certainly in the cardiovascular space, with some of these products. As Michael said, it is just a matter of time, and it’s probably in that five- to ten-year window.

Werner: Regenerative medicine products are already on the market; it’s not like all we have is academic INDs and that we are 15 years away from commercialization. There are products pretty far along, and as Morrie said there has been interest from major pharmaceutical companies — they wouldn’t be part of our group if they weren’t interested. I think the interest will build on itself. That is when we are really going to see advances.

About the Author

Author Details
Maribel Rios is managing editor at BioProcess International; 1-957-646-8884; [email protected]

REFERENCES

1.) 2006. 2020: A New Vision: A Future for Regenerative Medicine, US Department of Health and Human Services.

2.) Feigal, E. 2012. Communications with the Food and Drug Administration on a Development Pathway for a Cell-Based Therapy: Why, What, When, How. Stem Cells Trans. Med. 1:825-832.