Road MAPPs to therapeutic innovation

One of the original thought leaders of the concept of Adaptive Pathways was the NEWDIGS initiative of MIT’s Center for Biomedical Innovation. ADAPT SMART has had the pleasure of collaborating with NEWDIGS throughout.  ADAPT SMART interviewed NEWDIGS Strategic Director Mark Trusheim about the interactive case study he will facilitate at the ADAPT SMART closing event, as well as some of their current research.

Duane Schulthess (DS): Thank you for your time Mark. Can you provide us with an overview as to what MIT’s NEWDIGS will be presenting at the ADAPT SMART closing meeting?

Mark Trusheim (MT): Thanks Duane. MIT’s NEWDIGS are going to facilitate a session using our Design Lab methodology, highlighting the insights and findings of an ADAPT SMART case study in the clinical area of the blood disorder beta thalassemia.

Today, beta thalassemia is treated with a very invasive course of blood transfusions with limited success and numerous complications. Several companies are working on gene therapies that can treat the condition, and NEWDIGS will present a case study of several of the findings of the MAPPs project, highlighting the key decision moments that occur in the evaluation of a MAPPs product.

ADAPT SMART has created six framework questions that need to be addressed at those key decision moments in time, and we’ll walk the attendees through those questions to determine how this particular beta thalassemia case study addresses the insights and questions raised by the MAPPs pathway, from discoveries through approvals and even once a product is on the market.

DS: So, regarding those six framework questions, are they ubiquitous and platform agnostic regardless of the type of clinical product that would enter a MAPPs pathway?

MT: Yes, the questions were designed to meet the needs broadly of a MAPPs pathway, regardless of the area of clinical application. They are;

  1. Can we define a target population with a high unmet need? Does the product hold sufficient promise to address the unmet need?
  2. Can a prospective iterative post- (initial) marketing authorisation development plan be proposed, developed, implemented, upon which all stakeholders can agree?
  3. Are there workable tools to ensure appropriate product utilisation?
  4. Are there workable ‘strategies’ for payers to exit, or alter the product’s use, if the product under-performs?
  5. Is there sufficient commitment and resources from relevant stakeholders to engage in the MAPPs process to follow the development all the way through the lifespan?
  6. Are there any critical aspects for pharmaceutical development, particularly manufacturing, that need to be considered?

DS: Is it the belief of the members of the ADAPT SMART project that if you can’t answer ‘yes’ to all six of these questions,  an adaptive pathway is probably not right for the product?

MT:  From our perspective and initial discussions, that is the finding and encouragement of the ADAPT SMART consortium.

DS: Looking at the six questions, there is a direct need and approach to address the concerns of payers. How have their needs been addressed practically?

MT: I think it’s great that everyone is recognising that for the MAPPs approach to work the stakeholders need to be actively engaged in this process early, and if you have key stakeholders who aren’t engaged, the chance for success and acceptance will be greatly diminished.

And this relates to question 5, too. Downstream, there are organisations which have historically been understaffed and are not resourced to participate in shaping the development pipeline. So, those resource constraints will also need to be addressed as to not cause stresses in those particular cases.

DS: Isn’t one of the key drivers of the need for MAPPs and ADAPT SMART the new therapies that are coming such as CAR-T and the next wave of Immuno-oncology therapies? So far, they’ve proven to be highly effective in certain populations, but they also require the quick capture of adverse event signals. Doesn’t this demand more tools like MAPPs?

MT: We’re finding in ADAPT SMART that MAPPs are a tool to both learn how to use the products best and also give patients access to the drugs as rapidly as can be appropriate. These new pathways can be very helpful to these new classes of treatments. If you don’t use these kinds of integrated approaches, delays are likely to occur as developers need more time to develop the evidence that’s required. Payers and physicians downstream may still have questions and no mechanisms by which to answer those questions currently. So, MAPPs proactively tries to help all stakeholders get answers to the issues most important to them while not delaying and hopefully by accelerating a patient’s access to these promising treatments.

DS: Have you seen a difference in the application and acceptance of Adaptive Pathways between biotechnology firms and large pharmaceutical companies? Are both the small and large companies embracing the approach?

MT: We’ve seen a significant interest in activity across all sizes of firms. What seems to be more indicative of their applying MAPPs is the characteristic of the therapeutic area that they are addressing. So, it seems that regardless if you’re larger or smaller, if you’re working in oncology or some of these new gene therapies, I don’t think it matters if you’re big or small.

DS: As you’re going to be dealing with the same issues regardless?

MT: Yes. If you’re working in cardiovascular disease or some other broad primary care indications, it’s highly likely that you’ll have a difficult time identifying a target population with high unmet needs, so they generally don’t get past the first question under the MAPPs criteria.

DS: The push for early stakeholder engagement is a key point of the Adaptive Pathway. Is there one stakeholder group that has greater importance?

MT: ADAPT SMART has worked hard to include all stakeholders, and we find that they all want to be doing the best they can to improve care. Everyone is trying to get the best products to patients as soon as is possible, and different stakeholders have different views as to what’s valuable and appropriate for patients. Patients themselves have differing opinions, ranging from those willing to take more risks and participate in clinical trials to those that are only willing to take therapies that have been used and approved for a very long time. We find that all the stakeholders are trying to balance these varying access and evidence needs, given those patient preferences.

DS: Once you have a product in the market under MAPPs there is a need for robust data collection to verify the long-term performance of the therapy. How has the ADAPT SMART consortium been working to develop these data collection and verification approaches?

MT: The ADAPT SMART consortium has been working to build trust amongst all the stakeholders, so they can agree that the commitments to create the evidence generation long-term will be fulfilled. Much of the attention has focused on the importance of the companies committing to the continuing evidence development, but there is also a need for the providers and payers to participate in the evidence generation, since post-authorisation, payers and providers hold most of the evidence of real world treatment and usage. Simply doing clinical trials is not the best way to monitor the use of these products over time and learn from them. So, it’s not just the companies that need to generate the evidence post-authorisation, but it’s also the fact that payers and providers need to open up their billing and clinical records for broader learning to occur in a collaborative way.

DS: Now, that is a political problem, not a technical problem. How have you been able to break down those political barriers in ADAPT SMART?

MT: ADAPT SMART has been making significant progress in having all the stakeholders begin to better recognise that they benefit by learning how they can continue to use the products more effectively over time. The principles of precision medicine aren’t just around molecular markers, but also need information on how dosing levels depend on a patient’s age, or comorbidities. There are also challenges to optimising the use of combinations of new therapies that physicians often do in practice on their own, but we’ve lacked the opportunity to learn from their practice of real world medicine. Mining that data is becoming more and more doable both technically and politically. Europe certainly has data protection issues that need to be addressed, but this can be managed within countries.

DS: One last question, given the project is drawing to a close, do you think Adaptive Pathways will now become one of the permanent tools in the regulatory tool kit?

MT: My sense is these adaptive principles are already being used by coalitions of willing stakeholders to move things to patients faster. There are managed entry and exit programmes in discussion in Europe, and there have been numerous experiments of them being applied to Adaptive Pathways. The willingness to experiment seems to be growing, but the application of new approaches has never been lock step across any geographic area. I think it would be unreasonable to think that every new eligible drug will follow an Adaptive Pathway, but it appears there is greater alignment and willingness now, as the new classes of effective, complex, and expensive therapies seem to dictate this type of collaboration.