The FDA’s Perspective

General Session IX: Developing a Bioartificial Alternative to Dialysis

The Roadmap Initiative

Murray Sheldon, MDCenter for Devices and Radiological Health

U.S. Food and Drug Administration

IDEAS INNOVATIONS IN DIALYSIS: Expediting Advances Symposium

Seattle, WashingtonAugust 21, 2018

It’s About the ^Patients

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This requires a Sense of Urgency5 Year Survival of Cancers and ESRD (by treatment)

Ref: Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2014/, based on November 2016 SEER data submission, posted to the SEER web site, April 2017.

United States Renal Data System. 2016 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2016.

Little has Changed Nearly 60 years in Dialysis Technology

1962 2018Outcomes Remain Poor

“If we are going to keep patients alive by artificial means, we then incur the responsibility to see that it is a good life and an enjoyable life.” – Willem Kolff, 1968, pioneer of hemodialysis and artificial organs

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• A supply of electric powero 1882 Commercial distribution of electric power

• A mechanism for keeping the filament from burning out too quicklyo 1882 Edison invents the carbonized bamboo filament,

suspended in a vacuum

• A filament that glows when an electric current runs through ito 1802 Humphry Davy attached a platinum filament to a

battery, causing it to burn brightly for a few minutes

Requirements for Artificial Light

“He did not invent the Lightbulb by improving Candles” –T.A. Edison

Timeliness

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• A supply of electric powero 1882 Commercial distribution of electric power

• A mechanism for keeping the filament from burning out too quicklyo 1882 Edison invents the carbonized bamboo filament,

suspended in a vacuum

• A filament that glows when an electric current runs through ito 1802 Humphry Davy attached a platinum filament to a

battery, causing it to burn brightly for a few minutes

Requirements for Artificial Light

“He did not invent the Lightbulb by improving Candles” –T.A. Edison

Timeliness

Eureka!

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KHI RRT Roadmap Timeline

White House Organ SummitJune, 2016

Draft Roadmap completed 3rd Q 2018

Kidney Health Initiative:Goals for RRT Roadmap

Convene a diverse group

of stakeholders, patients and

care partners, academics,

industry and regulators

Describe scientific,

technical, and regulatory

challenges for mechanical, cellular and

hybrid technologies

Create a set of design criteria

for future alternatives to

RRT

Identify ways to incorporate

patient preferences

and feedback on design features

Create a roadmap with

milestones and opportunities for creating a

bio-artificial or bio-engineered alternative to

dialysis

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The Roadmap as a Catalyst for Change• Solutions to existing systems are complex

‒ Breakdown the complicated questions into smaller steps – Establish design criteria and milestones– Determine whether the goal is incremental change or “disruptive” innovation

• Encourage Innovation in kidney disease‒ Coordinate regulatory and payment pathways to support commercial

viability and patient access‒ Impact policy makers to increase kidney research funding

o Increase awareness of the limited funding compared to other medical specialtieso Kidney research is underfunded compared to the cost of care

• A multidisciplinary approach is needed– Connect with outside experts in different fields for novel perspectives– Integrate the best science with a patient-centered approach– Bring hope to patients with kidney disease

• (Re)Building a Kidney Consortium (RBK): A Basic Science Research Initiative Consortium

led by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)o Optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell

types and their integration into complex structures that replicate human kidney function

• Other Cellular Technologies to Repair or Replace a Damaged Kidney o Understand the mechanism of proximal convoluted tubule (PCT) cells o Replicating renal functiono How to deliver or administer the cells

As part of a scaffoldAs biologic therapy- oral or IV

State of Science for alternative to Dialysis as renal replacement therapy

• Mechanical Approaches o Miniaturization

Wearable artificial kidney (WAK)

Automated Wearable Artificial Kidney (AWAK)

o Implantable devices Implantable renal assist device (iRAD)

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Technology Roadmap for Innovative Approaches to Renal Replacement Therapy

8/21/2018

Goals of the KHI RRT technology Roadmap:• Spur innovation in the RRT field• Attract industry/academic

investment in developing RRT solutions

• Encourage internationally oriented multi-disciplinary approach

• Accelerate availability and adoption of commercially viable solutions

• Ensure patient/care partner preferences are incorporated

• Optimize processes regarding reimbursement

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Key Strengths of the Roadmap

8/21/2018

Patient-Centered focus, with clearly delineated, patient developed vision of improved patient quality of life

Opportunities for Multidisciplinary Collaboration to attract and leverage technology development from diverse sources

Multiple solutions, various time horizons: near-term incremental improvements; longer-term disruptive breakthroughs

Common Design Requirements ensure that all solutions meet the same minimum technical expectations

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Future State: Improved QoL

• Minimized impact of therapy on family and social life• Improved ability to work and travel• Increased mobility and physical activity• Increased treatment choices• Liberalized diet and fluid regulation• Reduced medication burden• Reduced disease and treatment complications• Reduced financial impact

8/21/2018

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Enabling Change through Focused Research and Design

8/21/2018

• Technology solution-agnostic• Three focus areas Kidney Function: unique solutions for replicating each kidney

function (blood filtration, electrolyte homeostasis, fluid regulation, toxin removal/secretion, fluid transport/drainage)

System enablers: connect/integrate elements of RRT (RRT access, biomaterials, bio and immuno modulation, monitoring)

Supporting Activities: to ensure accelerated access to solutions (regulatory alignment, innovative incentives and payment pathways)

• Three time frames Near-term (2019 – 2022) Mid-term (2023 – 2025) Long-term (2026+)

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Despite some Early Successes, Overall Challenges Remain

• Knowledge gaps exist– Cellular functional abnormalities that can be replaced by producing a filtration device

connected to a device with differentiated epithelial cells that will process filtrate – What is minimal or optimal RRT to minimize uremic symptoms and consequences– Animal uremic models which model human ESRD to test efficacy of devices – What components of uremia “have to be replaced” and which ones can be treated with

drugs or other ways? What can be replaced conventionally (i.e., EPO, Vitamin D)

• Understanding diverse patient needs– How to include unrepresented patients’ preferences– Patients’ risk tolerance varies

• Those that want change now (even if incremental; e.g. 1X/week vs. 3X/week) • Those that want a big game changer (even if they have to wait)

• Financial/reimbursement– Future of the bundled payment system; how new technologies will get reimbursed– ESRD Seamless Care Organizations (ESCOs)

• Regulatory clarity– Need for large animal studies before human trials

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How the Roadmap relates to KidneyX

• Supports coordination across HHS Agencies (FDA, CMS and NIH) to clarify the path toward commercialization and patient access to innovative products

• Provide merit based, non-dilutive funding via a series of prize competitions

• Kidney Innovation Accelerator (KidneyX) is a public-private partnership between HHS and ASN intended to accelerate breakthroughs and innovations in kidney care

• The RRT Roadmap will guide the priority funding choices of KidneyX 1.0

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Traditional Funding Model

8/21/2018

Funding Organization/

Agency($$$)

The funding/innovation organization sending its money and concepts into the community…

…does not necessarily result in the development of a functional collaborative community.

Funding Organization/

Agency($$$)

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Funding Organization/

Agency($$$)

KidneyX Funding Model

Funding Organization/

Agency($$$)

The funding/innovation organization using its money and concepts to attract innovators into its community…

…has a much better opportunity to development of a functional collaborative community.

Funding Organization/

Agency($$$)

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We Joined the KHI Roadmap!

8/21/2018

If you want to go fast, go aloneIf you want to go far, go together

What Can You Do?

CAN WE ADD YOU TO THE PARTNER LIST?17