FDA’s Access Mechanisms - PowerPoint Presentation

1. FDA’s Access MechanismsWhen They Work – When They Don’t And WhySteven WalkerCo-Founder, VolunteerAbigail Alliance for Better Access to Developmental DrugsKakkis Everylife Foundation Panel – March 27, 2014How Patients Can Work With FDA and Industry on Expanded Access, Compassionate Use and Emergency INDs

2. FDA PERSPECTIVE2FDA – Access Sometimes OK If:Drug is Being Developed (e.g. ongoing clinical trial development program – preferably in same or very similar indication)No Significant Interference with Trial EnrollmentRisks to Patient Deemed Acceptable or ControlledAll Required Applications are Submitted/Reviewed/Approved by FDAInformed Consent is ObtainedInstitutional Review Board Approval ObtainedFDA Flexibility?Some Flexibility for Emergency and Single-Patient INDs (Compassionate Use)Much Less Flexibility for Treatment INDs (Expanded Access Programs)FDA Legal Authority and TransparencyAuthority is Absolute – No FDA Approval – No Access – Period!FDA is Opaque (in part required by law) – Patients/Public Learn Backstory Only if Sponsor Provides Insight

3. INDUSTRY PERSPECTIVE3Industry –Sometimes Agree to Provide Access If:Consistent with Company Policy/Philosophy/Investor WishesThink or Strongly Think Drug May Be Safe/Effective for Proposed UseHave Ability/Willingness to Manufacture Needed Quantities of Investigational DrugHave Needed Financial and Personnel Resources to Administer ProgramWilling to Accept Uncertainties Associated with Allowing AccessMust Decide Whether to Provide Access to All? - Some? - Only a Few? - Only One?Must Decide Whether to Provide for Free? - or to Charge? Company Can’t/Won’t Provide Access if :FDA Won’t Approve - or is Strongly Discouraging - Access Clinical Development Program Requirements Make Access Program Infeasible (e,g., If FDA is requiring large randomized controlled study(s), need to enroll/complete studies first)Level of Confidence that Development/Regulatory Pathway to Approval Is DefinedIndustry Legal AuthorityNo Legal Authority – Can Only Provide Access After Complying with FDA Requirements and Receiving FDA Approval – Even for a Single Patient

4. PATIENT PERSPECTIVE4Patient SituationDealing with Serious/Life-Threatening Diseases with Unmet Medical Need And:No Approved Treatment Available No Clinical Trial or Trial EligibilityUsually - No Existing Access ProgramWaiting is Not a Reasonable Medical OptionPatient RationaleObtaining Access to a Promising Investigational Treatment Represents:Only Reasonable Medical Treatment Option Other Than Palliative CareBest Potentially Available Medical CareRational and Well-Considered ObjectivePrecisely the Same Objective Sought by a Patient/Family Who Succeeds in Entering a Clinical Trial for an Investigational DrugSame Risks – Same Potential for BenefitRisk of Disease Substantially Outweighs Risk of Treatment With an Investigational DrugEyes Wide Open! Patient/Family in Best Position to Weigh Risk/Benefit

5. Single-Patient IND5It’s all on the patient/family Try to find a trial – failIdentify the investigational drug(s) that pose the most potential for benefitThere is no mechanism for a patient/family to request access on own behalfFind a physician willing to be the sponsor, and request and administer the drug Convince the company to provide the drug and assist the physician in applying for FDA approvalMost Attempts End Here – FDA Does Not Count as a Request for AccessIf successful – wait - often for weeks or monthsWait for application to be prepared and submittedWait for FDA review/approvalSeek and obtain IRB approvalIf Approved – Wait another 30 days to receive treatment unless FDA waives waiting period

6. Treatment IND6It’s all on the companyRegulatory Submissions for Approval Approach Requirements of Application for Marketing ApprovalUsually Not Considered Feasible Until All FDA Required Clinical Trials are Completed and Approval Application Process is UnderwayIf FDA Approval of Drug is Uncertain – Starting Program Can Carry Substantial Financial, Procedural and Ethical Risks for SponsorTakes Time to Set Up – May Not Actually Launch Before FDA Decides on Application for Marketing Approval$$ Expensive $$ - All costs usually borne by companyTreatment INDs (aka Expanded Access Programs) are:RareUsually Started Very Late in the Development ProgramUsually Small Have Restricted EligibilityGenerally Underserve the Patient Community with a Legitimate Need for Access

7. Why So Seemingly Dysfunctional?7Investigational Drug Access Programs are Designed to be Exceptions to the FDA’s Authority to Prevent Marketing and Use of Unapproved DrugsFDA Insists on Directly Regulating the Provision of Any Investigational Drug to Any Patient – Even for a Single Terminal Patient with No Other OptionsFDA Considers Enrolling and Completing Clinical Trials for Investigational Drugs to Be Its Core Functi0n in Establishing Safety and Efficacy for Purposes of a Marketing ApprovalThe FDA believes that its preferred Phase III clinical trial design – the randomized controlled trial – often blinded and placebo-controlled – might be difficult to enroll and complete if an investigational drug is available by other means

8. The Blame Game8Why Can’t I Get the Investigational Drug I Need? FDA Blames the Drug Company – Says/Implies Agency Would Approve ItThe Drug Drug Company Blames the FDA – Says/Implies FDA Won’t Approve ItThe Half Truth – And Nothing But the Half Truth!

9. Bottom Line9The FDA’S Investigational Drug Access Mechanisms Seem Dysfunctional to Patients Because They are Designed and Intended to Be Relatively Rare ExceptionsFDA’s Authority to Regulate Medicines is Based Primarily on Its Power to Say NoFDA Believes That If It Allows Broad Access to Investigational Drugs or Approves Drugs Before All the Clinical Trials it Wants Are CompletedSome of the Data the Agency Believes Should Be Collected May Be UnobtainableThis Tension is Created Primarily by the FDA’s Still Rigid Requirements for Completion of Randomized Controlled Trials (Often Blinded and Placebo-Controlled) Prior to Considering an Application for Approval of Most New DrugsUnderstandably – Patients with Serious and Terminal Diseases Would Rather Get the Drug Than a Sugar PillThe Solution is Access Mechanisms Designed to be Real Medical Delivery Options Coupled With Smarter, More Scientific, More Ethical Trial Designs – a Related and Extremely Important Subject for Discussion

10. Working With FDA and Industry On Access10The tough news – in most cases – is that you are on your ownThere are presently no financially-resourced, non-profit or for-profit organizations providing services to patients seeking access to investigational drugs – because there is usually no functional pathway for them to followIf there is no Treatment IND, and initial attempts to gain access through a Single-Patient IND fail – try to work directly with the drug company and the FDARequest face-to-face meetings, and keep requesting them until you get them. Start at the top – drug company CEO’s and the Commissioner’s office at the FDANetwork and organize with fellow patients and families, and use the mediaRemember that the FDA has no drug to give you - but may very well be the reason – either directly or indirectly – behind the drug company’s denial of access. Focus your efforts on understanding the position of the drug company and working with them to make provision of the drug you need a workable option for them

11. The Hard Reality11If you are seeking access to an investigational drug outside a clinical trial for a serious or life-threatening condition – then you have fallen into a severe gap in our health care system FDA’s access mechanisms mostly don’t work by design and intentThe more likely outcome is that if initial efforts fail, you will not gain access to the investigational drug you seek, and if you do – it may take a long time – sometimes too long - for that access to become availableMake contingency plans and pursue them in parallelOne of those contingency plans should be for all patients and families facing this dilemma to get involved in solving it for everyone

12. 12Abigail Alliance for Better Access to Developmental Drugswww.abigail-alliance.orgSee the DocumentaryFight to LiveDirected by the Academy Award Winning Film-MakerBarbara Kopplewww.fighttolive.orgAvailable on iTunes, Google Play and Most Cable On-Demand Movie Channels