@ALSETF #EAP2015. Jess B. Rabourn CBI Expanded Access Conference July 22, PDF Free Download

How to Win Physician Collaboration Models for Advancing Access to Lifesaving Therapies @ALSETF #EAP2015 Jess B. Rabourn CBI Expanded Access Conference July 22, 2015

How to Win Now that we want Expanded Access. How do we launch programs that: Reach a meaningful number of patients Do not interfere with clinical research Benefit all involved parties (Drug Co., HCPs, patients, public)

How to Win A New Way Forward Partnerships of Aligned Interests

Agenda Intro History / Practice Feasibility Factors Cost Recovery Third Party Model Mechanics +10 min. Q&A

Why Expanded Access Why is Expanded Access needed? 1938 Food, Drug, & Cosmetic Act (FDCA) Prohibits use of new drugs before approval (interstate commerce) 1962 Kefauver-Harris Amendment to FDCA Requires substantial efficacy evidence before approval One-size-fits all: struggled to differentiate cancer from common cold Investigational New Drug (IND) exemptions for clinical research

Post-1962: FDA Gets It! Special exemptions for life-threatening situations 1962-1987 Tropical Disease IND Orphan Drug IND Open Label IND Group-C IND Compassionate IND Emergency IND Treatment IND 1987 Promulgation: Expanded Access Treatment IND Emergency IND & Individual IND 1992 FDA / PHS Statement Parallel Track 1990/1997 Devices (HDE / T-IDE) 2009 Final Rule Treatment IND Intermediate-Size IND Emergency IND & Individual IND

Current Access Channels Special exemptions for life-threatening situations 1962-1987 Tropical Disease IND Orphan Drug IND Open Label IND Group-C IND Compassionate IND Emergency IND Treatment IND 1987 Promulgation: Expanded Access Treatment IND Emergency IND & Individual IND 1992 FDA / PHS Statement Parallel Track 1990/1997 Devices (HDE / T-IDE) 2009 Final Rule Treatment IND Intermediate-Size IND Emergency IND & Individual IND

The Right Channel for the Situation Protocol-Driven Expanded Access Compassionate Use Treatment IND or protocol amendment Intermediate-Size IND or protocol amendment Emergency-Use protocol (For many) Individual Patient IND Emergency Use IND (1-time) For a class or condition affecting more than one patient. Many patients per IND Sponsored by drug company or third party Exceptional / Rare: Bat bite, unexpected reaction / infection, etc. n=1 One patient per IND, handful of patients in total Sponsored by physician Centrally managed and monitored, like research study No central management Standardized dosing, observation, data collection Each MD may write individual protocol, no valuable data

Myth and Reality Exploratory Treatment Access FDA Form #1572 or #3926 Exploratory Treatment Access Right To Try Exploratory Treatment Access = Feasible campaign to sponsor and conduct EAP Feasibility = f ( fiscal reward & cost, valuation reward & cost, risk)

Agenda Intro History / Practice of EA Feasibility Factors Cost Recovery Third Party Model Mechanics + 10min Q&A

Feasibility: Drug Company (Sponsor) Hard Costs Supply Chain Regulatory Prep Site Activation, IRB, ICF Protocol, IB, Training Pharmacovigilance, Safety DB Medical Monitoring Public Communication Insurance /Indemnification Coordination Hazards usae E&O / Malpractice Budget Shortfall Public Perception Favoritism Withholding Promotion Profiteering Rewards Engagement / Familiarity Safety Data Research Outcomes Human Mission Elective Costs Cost to Support Sites Research (endpoints, EDC, data) Patient Assistance Funding

Feasibility: Health Care Provider Resource Expenditures -IRB / ICF Review -Screening, Enrollment -Pharmacy / Accountability -Administering Product (i.v., peg) -Lab - tox -Medical Evaluation -Record Keeping -Coordination / Training Negotiated Costs For: -Tax for Institution -Margin (Overhead) -Research Endpoints -Data Collection / CRF entry Rewards -More options for treating patients -Familiarity with drug -Learning outcomes (Responder subgroups) -Publication / Visibility Other Considerations -Patient Selection -Informed Consent / Expectations -Safety

Feasibility: Determinants 1. Inherited Cost of the product (mfg, finish, storage, shipping) Scale of existing supply process Route of administration (i.v., peg, intrathecal) Safety of the product (monitoring, usaes, regulatory) Prospect for patient benefit 2. Strategic Cost recovery? Research / Endpoint collection? Partnership?

Agenda Intro History / Practice of EA Feasibility Factors Cost Recovery Third Party Model Mechanics + 10min Q&A

What Costs? What is the total cost of an access program? Product Supply Costs Mfg, finish, labeling, storage, shipping Program Management Costs Regulatory Site activation and monitoring Pharmacovigilance / Reporting Medical monitor -------------------------------------------- Per Site: IRB / ICF Review Record Keeping Training / Coordination Patient Treatment Costs Administration of study drug, observation, lab safety Pharmacy, drug handling and accountability Screening, medical visits Research Costs Endpoint measurement / CRF Imaging, biosample collection Lab analysis Data management / analysis

FDA and Cost Recovery Q: What can the sponsor charge to patients or payers? A: Any direct, incremental costs associated with providing study drug. Supply chain costs Central monitoring costs & program mgmt Product Supply Program Mgmt Caveat: No Profit Prior authorization required; annual basis Must not interfere with progress toward market approval 21 CFR 312.8 (c): Charging for expanded access to investigational drug for treatment use. 21 CFR 312.8 (d): Costs recoverable when charging for an investigational drug.

FDA and Cost Recovery Q: What services can the HCP charge to patients or payers? A: It is up to the HCP and its IRB. FDA authorization is not needed. Patient Treatment Costs Administration of study drug, observation, lab safety Pharmacy, drug handling and accountability Screening, medical visits -------------------------------------------- 21 CFR 312.8 (c): Charging for expanded access to investigational drug for treatment use. 21 CFR 312.8 (d): Costs recoverable when charging for an investigational drug.

How much is on the sponsor? Simplest, clinical trial model Partnering with HCPs with cost recovery (Kyprolis, 2011-2012) (Gleevec, 2000-2003) (Voraxaze, 2007-2010) Sponsor pays 100% Sponsor pays minimum Patient Treatment Product Supply Product Supply Program Mgmt Program Mgmt Research Research Research

How much is on the sponsor? For a SCALABLE-SIZE program, in areas of great unmet need: 1. PARTNERSHIP between Sponsor and HCP. (not vendor / client) 2. Consider recovery of product costs & mgmt costs.

Agenda Intro History / Practice of EA Feasibility Factors Cost Recovery Third Party Model Mechanics + 10min Q&A

Sponsoring an EAP The Sponsor of an EAP is responsible for: Regulatory Filing Procurement of Investigational Product Medical Monitoring and Reporting Site Selection and Clinical Operations

A Platform for Exploratory Medicine in ALS ALS Emergency Treatment Fund (ALS-ETF), a 501c3 non-profit corporation Founded in 2012 with help from patients and patient advocates Created to work in partnership with drug companies, leading disease foundations, and participating clinics Project budget for EAP management, infrastructure, patient assistance fund. *Learning From Patients* initiative for predictive marker discovery, using outcomes data from interventional studies and matching biosamples Network of bioassay and informatics vendors EAPs to provide valuable additional patient data

A Third Party Sponsor is Better ALS Emergency Treatment Fund (ALS-ETF): Specialist in Expanded Access Strong Connections in the Medical Community Structurally Aligned with Patients and their Doctors Research Overlay to Generate Valuable Data Large EAPs = Large n marker-discovery trials, in cohorts that are more representational of disease population.

Agenda Intro History / Practice Feasibility Factors Cost Recovery Third Party Model Mechanics + 10min Q&A

ALS-ETF Case View A Collaboration with HCPs for an Expanded Access Program in ALS Sponsor = ALS-ETF, under agreement with drug company. Medical Advisory Board Steering Committee ( as DSMB)

ALS-ETF Case View Program Synopsis: Monthly regimen (i.v. infusion, outpatient) Ongoing treatment (chronic / renewable period) Monthly / Quarterly medical evaluation 1 clinical endpoint + 1 spirometry measure Baseline and 6month blood-sample ********************************************** 100 patients in U.S. program 5-10 sites (5-20 patients at each site) Enrollment: Fixed number for each site By physician; 1 st come 1 st served (No random selection) Subject to inclusion/exclusion criteria

This is NOT funded research Drug Product and Materials: Provided to site at no charge HCP s expense for coordination / data entry / record keeping: $10k - $50k subsidy for each site IRB fees, study team fees, site fees: waived Patient Treatment Costs Recovered by HCP from payers / patients

ALS-ETF Case View 1. Neither party extracts profit margin 2. Product and grant subsidy to HCP 3. Patient transacts ONLY with HCP 4. HCP recovers its own per-patient treatment cost = Feasibility & Scalability

Who pays for patients treatment? Patient Treatment 1. Absorbed by HCP 2. Medicare Part B 3. Private Health Insurance 4. Patient / Patient Assistance

Who pays for patients treatment? Default Case: Billing patients Many HCP services are ineligible for reimbursement Charging just for treatment services, not product ALS-ETF negotiates low rate, close to breakeven Patient Assistance Fund via means test (xfpl) Collaboration: Sponsor agrees with sites on billing practice.

Who pays for patients treatment? Billing CMS and private insurance: Medicare Part B analysis; National Coverage Determination Protocol-specific, Region-specific Private payer: Special pre-authorization required Policy language on situations of need Standard of Care vs. Research Collaboration: Sponsor and site support NCD Coverage Analysis; Negotiation with private payers led by sponsor and clinic consortium.

The Research vs. Care Trap Institution Funding Office Research Unit EAP Sponsor Specialty Clinic Hospital Svc s

Sponsor s Cost Recovery? Product Supply Program Mgmt 1. Patient / Patient Assistance Direct Txn between patient and sponsor? Or, bill through clinic? Add on to medical billing. Order management tie-in with A/P, A/R. 2. Traditional Payers Very difficult; involve patient advocacy / lobby

Industry / HCP Collaboration Work together to write institutional policies for humanitarian, protocol-driven access programs. i.e. NOT funded research! Choose sites who will bill out for their treatment services. Also, consider cost recovery for product and central management. Work with medical community and with advocacy to improve reimbursement landscape. Third Party Platform as sponsor Specialist, more efficient Better negotiating position Community resources available Shields company from financial / operational burden

Agenda Intro History / Practice Feasibility Factors Cost Recovery Third Party Model Mechanics + 10min Q&A

@ALSETF #EAP2015. Jess B. Rabourn CBI Expanded Access Conference July 22, 2015