Q&A With C-Path CEO Dan Jorgensen and Chief Scientific Officer Klaus Romero

Dan Jorgensen, MD, MBA, MPH
CEO
C-Path

When the FDA drafted the Critical Path Initiative 16-odd years ago,¹ it did so because the process of drug development in this country needed help. The agency’s dual mandate of ensuring that the safety of new drugs and devices outweighed the risks, while simultaneously promoting innovation, was in conflict. Former FDA director Janet Woodcock wrote in 2008 that this drove the genesis of the Critical Path Initiative.² The Critical Path Institute (C-Path) resulted from that initiative. C-Path, a public-private partnership, now has offices in Arizona and Amsterdam and its presence is well established in PubMed. CEO Dan Jorgensen, MD, MBA, MPH, who joined C-Path last fall, and longtime C-Path researcher Klaus Romero, MD, MS, chief scientific officer and executive director of clinical pharmacology spoke with Medical Device & Technology.

(MDT:) Dr. Woodcock wrote in that 2008 article that medical researchers “are using the tools of the last century to evaluate this century’s advances.”What is C-Path’s role in effectively translating new research into marketable treatments?

Dr. Jorgensen: As a public-private partnership, C-Path can pre-competitively accelerate medical product development. We now have 26 consortia and programs and a total of 1,600 scientists working within them, representing regulatory agencies and biopharma. They have come together to solve problems in a particular disease state or another area of interest like data collaboration. Major areas of interest are biomarker development, data analytics, and the repurposing of medications. We started the Cure Drug Repurposing Collaboratory soon after the pandemic started.³

Klaus Romero
Chief scientific officer
C-Path

Dr. Romero: The FDA’s vision, which has stood the test of time, was to properly identify the hurdles and bottlenecks that have hobbled the way of efficient, effective drug and device development. They saw that the best way to resolve these problems would be through community effort. The growth of the consortium portfolio is testament to that.

(MDT:) How are these consortia formed?

Dr. Romero: The interested parties come to us. We receive about eight requests per quarter. We do a feasibility stage assessment to see whether we should proceed. For that to happen, three things need to align: Does the project fulfill an unmet need, will the solution to the unmet need be achieved with existing data or future data, and will that data be feasible to integrate? If the funding is there–consortia members contribute–then we link FDA, industry, and patient voices into one group.

Each consortium has its own governance body made up of paying members. We provide a venue for consensus to happen. We align the members on which hurdles to fix first. Nothing we do is done in a vacuum.

(MDT:) Would you discuss the bottlenecks that have been resolved?

Dr. Romero: We have been successful in solving problems of process which have led to other findings. We have taken work that we have done with one disease state, such as polycystic kidney disease (PKD), and then have applied it to others like type 1 diabetes and Alzheimer disease.

(MDT:) These diseases are similar from a pathology perspective?

Dr. Romero: Pathologically no, but they possess similar bottlenecks that have held back progress. In these diseases, there is a push for its prevention, to identify the disease earlier, way before diagnosis–and to develop treatment. These diseases have many stages which complicates patient selection, mainly because of the dosing issues.

(MDT:) C-Path has worked on refining patient selection strategies?

Dr. Romero. Our goal has been to find actionable biomarkers that can help identify patients with factors relevant for drug development. A great example is what we did for patients with PKD. We started with a clear understanding of the quantitative relation of total kidney volume, via imaging, and disease progression.⁴ That evidence was submitted to the FDA and the EMA for the endorsement of total kidney volume as an enrichment biomarker. That evidence was then combined with trial data, leading to TKV being designated as a reasonably likely surrogate by FDA. What is important is now we know where the solutions are and we can invest in a pipeline.

(MDT:) How important are digital biomarkers?

Dr. Jorgensen: We have put a lot of effort and time into digital health tools. They have been prominent in our work on Parkinson’s disease (e.g., smartwatch monitor) and type 1 diabetes (e.g., continuous glucose monitor). They are increasingly being accepted in the medical product development process. We are working to transition their role to become endpoints in clinical trials. In general, our work on biomarkers has been well received. In 2018, the data that our predictive safety testing consortium and the NIH’s biomarkers consortium received FDA qualification, the first of its kind.⁵

Dr. Romero: There is a big push for clinical trials to run in a decentralized way and a key aspect of that success is digital health technologies. In addition to what Dr Jorgensen has mentioned in type 1 diabetes and Parkinson’s, our consortia are working to develop an activity monitor-based endpoint measure of physical activity for adults with congestive heart failure.

(MDT:) Please discuss your work on tuberculosis.

Dr. Romero: We were approached for this consortium circa 2010–the last drug developed for TB was 50 years before that. There was nothing novel for this disease on the market. The other issue was that to successfully treat TB, you need a combination of antivirals. We started integrating data developed with a series of solutions and tools, all of which contributed to the accelerated approval of bedaquiline in late December 2012 which eventually was combined with other medications for the treatment of TB. Again, this new medication led to a growth in the drug development pipeline to test other therapies for TB.

(MDT:) Do you keep a database that all the consortia can consult for problem solving?

Dr. Jorgensen: That is applicable to any good organization. Sometimes there is a risk of silos or categories within organizations that are not interacting with one another. We want people to learn from each other.

References

1. Woodcock J. Cossman J. (January 2007) Drug Development and the FDA’s Critical Path Initiative. ClinicalPharm & Therapeut 81;1
2. Woodcock J, Woosley R. (2008) The FDA Critical Path Initiative and Its Influence on New Drug Development. Annu. Rev. Med. 2008. 59:1–12.
3. (June 23, 2020) CDRC: C-Path Launches CURE Drug Repurposing Collaboratory to Accelerate Identification of New Uses of Existing Drugs to Treat Infectious Diseases, Including COVID-19. https://c-path.org/c-path-launches-cure-drug-repurposing-collaboratory-to-accelerate-identification-of-new-uses-of-existing-drugs-to-treat-infectious-diseases-including-covid-19/
4. Izmailova ES, Maguire RP, McCarthy TJ, Müller MLTM, Murphy P, Stephenson D. (March 16, 2023) Empowering drug development: Leveraging insights from imaging technologies to enable the advancement of digital health technologies. Clin Transl Sci. (3):383-397.
5. (October 25, 2018) FNIH Biomarker Consortium and Critical Path Institute Achieve the First Ever Qualification of a Clinical Safety Biomarker by the U.S. Food and Drug Administration. https://fnih.org/press-release/fnih-biomarkers-consortium-and-critical-path-institute-achieve-the-first-ever-qualification-of-a-clinical-safety-biomarker-by-the-u-s-food-and-drug-administration/