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Blog Anke van Engen

Regenerative medicine (RMx) has been gaining attention in recent years, as both big pharma and small biotech invest more time and resources into developing these new therapies. Yet there is still a lot of uncertainty about how to demonstrate the value of RMx products to regulators, payers, HTA organizations, patients and physicians, and that’s creating a lot of risk for leading innovators as they shepherd these therapies to market.

At a recent New York Pharma Forum event, I was part of panel discussing the unique market access obstacles RMx products face, and the prevailing message of that session was clear: All developers face pre- and post-launch challenges, but only the ones that are prepared with the appropriate evidence package will be poised to dominate in this field.

RMx is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects. These treatments generally fall into three categories: cell based therapies, in which cells are extracted, processed, and reinfused in the patient; gene therapies, in which therapeutic DNA is directly introduced into the patient’s body to correct the tissues function; and tissue engineering, in which cells are cultivated into a matrix to generate 2D and 3D grafts that can be implanted into the patient.

The potential benefits of regenerative medicine are huge – enabling patients to heal their own damaged tissue and addressing the shortage of donated organs. However, due to the increased complexity of developing and applying these therapies, they face significant approval and market access challenges.

The RMx journey

RMx is still a relatively new treatment category and there are so few case studies that developers can use to chart their path to market. The lack of evidence from previous RMx products and limited experience among regulators make drafting of policy and guidelines cumbersome. Similarly, the lack of history and increased procedure complexity make it difficult for payers and HTA bodies to conduct reimbursement evaluations. All of these factors add complexity for developers who may be required to conduct more extensive clinical research or multiple coordinated interactions with the same patient to demonstrate safety and effectiveness.

These obstacles have prevented many promising RMx products from gaining a foothold in the marketplace. In one of the most highly publicized examples, Provenge®, a breakthrough RMx Prostate cancer vaccine developed by Dendreon, faced years of delays in gaining market approval. Despite the fact that developers were able to demonstrate improved survival rates in prostate cancer patients in 2002, and by the year 2007 it had extended survival data from several clinical studies and endorsement by a federal advisory committee, the FDA didn’t approve the product until 2010. The regulatory delay coupled by a tempered market response due to administration and reimbursement complexities, stymied access to an innovative technology, and ultimately pushed Dendreon into bankruptcy.

Provenge is an extreme example of the high bar that RMx therapies face in gaining market access, though it’s not an anomaly. Treatments in this category, such as the much anticipated CAR-T cell therapies for the treatment of leukemia and lymphoma, might face an uphill battle to win regulator, payer and provider support – but it can be done. To get there, developers need to plan their market access strategy well in advance, engaging all of the key stakeholders throughout their research and clinical development process. Here’s how to do it.

RMx Access: A Seven Step Plan to “Value-proofing” an Asset

  1. Take stock of all your stakeholders. Identify regulatory bodies, HTAs, payers, physicians and especially legislators who have the power to develop policies that may facilitate or deter adoption of your RMx product. Such policies can take years or more to put in place so the sooner you get them on board the better. For example, The House of Lords in the UK, recently published a comprehensive report providing advice on how to enact appropriate and streamed lined regulation, promote integration of academic, commercial, and healthcare expertise, and champion a model that enhances bench-to-bedside translation of RMx products.  
     
  2. Evaluate precedent cases. There may not be many, but the success stories that do exist can offer valuable insight into what works and what doesn’t work when bringing an RMx product to market. Pay attention to the data required to gain approval including lab tests, rea-world effectiveness data, sub-population analysis, and demand for comparators, and use those examples to inform your own research. Companies can learn from examples such as Dendreon, where regulatory delays and reimbursement challenges significantly undermined the product’s commercial potential.  
     
  3. Be transparent about what you can and cannot do, while solving for efficient evidence generation. Regulators may want certain types of data, such comparator studies and long term evidence of safety, that you cannot provide. Be up front with them as soon as you identify a data gap, so you can have frank conversations about what alternatives to pursue, what additional studies may be required to close the gap, and whether it’s worth moving forward based on their feedback. Real-world evidence platforms represent a potential cost-effective means to integrate observational data and enable post-marketing studies of benefit-risk, value, and long-term outcomes.  
     
  4. Think about value as well as safety and efficacy. HTA bodies focus on the clinical and economic value of the product relative to current clinical practice, and their assessment will determine whether your intervention is valuable and worthy of the suggested price compared to existing products. Do not underestimate the importance of their support, and make sure you have the data to back up your value message so you can secure a positive review and a price that will generate a return on innovation. RMx technologies need to be valued holistically by stakeholders, including clinical, economic, and humanistic value. These innovative products hold the promise of permanently restoring tissue and organ function and, as such they should be highly valued; however, due to their increased complexity of manufacturing and delivery, their cost-effectiveness is difficult to appraise.  

  5. Meet with physicians and centers of excellence.Talk to physicians about how patients are being treated today, how they are reimbursed, and what quality measures they are being judged on to ensure the value proposition of RMx treatments is relevant to their needs. For example, if they are judged on length of hospitalization, or the speed with which results are achieved, you need to prove that RMx treatments address these measures to gain their support. Having these data at the beginning of your own research and development endeavours ensures you will capture the data points that are most meaningful to clinical stakeholders in the market place.  

  6. Talk to the labs. RMx therapies are often harder to evaluate and test, and additional educational efforts might be required. You also want to understand how the labs interact with the provider so you can optimize that process and ensure that every additional pathway of the treatment journey, including biopsies, biomarker tests, and procedures are reimbursed.  
     
  7. Educate patients.Patients today play a much bigger role in deciding which treatments they will embrace and pay for – so be thoughtful about the patient’s experience with your treatment. Talk to them about the risks they are willing to accept and the benefits they expect in exchange, and make sure they understand how RMx treatments work and what value they can bring to their quality of life. Measure these indirect and intangible benefits to patients.  Taking the time to interact with patients can help you win over the advocate community and demonstrate to regulators, HTAs and payers that you understand and have addressed their needs. Patients will increasingly modulate the market for RMx therapy in consumer-driven healthcare.