Seriously Ill Patients' Access to Experimental Therapies

8/9/2019 Seriously Ill Patients' Access to Experimental Therapies

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Terminal or Seriously Ill Patients· Terminal or Seriously Ill Patients·

Ability to Access Experimental Ability to Access Experimental

Therapies Therapies

By I&C President Ryan WittBy I&C President Ryan Witt

[email protected] [email protected]



R ememberR emember

Ask Ask QQss

Always Always ask ´ Why/how, What, and Whenµask ´ Why/how, What, and Whenµ

Try to Try to understand EVERYTHING!nderstand EVERYTHING!



Access to what? Access to what?

The ability of a person The ability of a person, who has a, who has a disease with no approveddisease with no approvedtherapy availabletherapy available, to access a therapy while it is in its, to access a therapy while it is in itsexperimental stages of study either in that study experimental stages of study either in that study or or outside of outside of that study.that study.



Four Methods of Access toFour Methods of Access to

Experimental TherapiesExperimental Therapies1.1. Clinical TrialsClinical Trials

2.2. Expanded Access (E A) programsExpanded Access (E A) programs

3.3.

Compassionate Use (CU ) protocolCompassionate Use (CU ) protocol4.4. Emergency UseEmergency Use



Clinical Trials (C Ts)Clinical Trials (C Ts)

Studies in humans, often to determine a therapy orStudies in humans, often to determine a therapy ordevice·s safety and efficacy (the ability to produce andevice·s safety and efficacy (the ability to produce aneffect ).effect ).



Phases of TestingPhases of Testing

There are There are 3 phases3 phases in Clinical Trials prior to FD A approvalin Clinical Trials prior to FD A approval

PreclinicalPreclinical ² ² cell culture and in animalscell culture and in animals

Phase 0Phase 0 ² ² 1010--15 patients to study if drug works the way it·s15 patients to study if drug works the way it·sexpected, based on preclinical studies; no data onexpected, based on preclinical studies; no data on

safety/efficacy safety/efficacy

1.1. Phase IPhase I ² ² maximum tolerable dose, safety, and metabolismmaximum tolerable dose, safety, and metabolism

2.2. Phase IIPhase II ² ² safety and effectiveness (200safety and effectiveness (200--500 ppl )500 ppl )

3.3. Phase IIIPhase III ² ² safety and effectiveness compared to SoC ( 500safety and effectiveness compared to SoC ( 500--

2000 ppl )2000 ppl )FD A Marketing Approval (exclusivity )FD A Marketing Approval (exclusivity )

Phase IV Phase IV ² ² postpost--approval safety surveillanceapproval safety surveillance



Why do we care? Why do we care?

Seriously ill patientsSeriously ill patients ² ² no effective or safe therapy no effective or safe therapy

CTs represent the most innovative therapies available.CTs represent the most innovative therapies available.

In the case of current technology, this isIn the case of current technology, this is ---- Targeted therapies Targeted therapies

Bivalent antibodiesBivalent antibodies

Novel inhibitorsNovel inhibitors

Gene Therapy with innovative delivery techniques and payloadsGene Therapy with innovative delivery techniques and payloads



Enrollment in Clinical TrialsEnrollment in Clinical Trials

However, despite this benefit«However, despite this benefit« FEW FEW with serious illnesses take with serious illnesses take

advantage of this opportunity.advantage of this opportunity.

For cancer: an estimated 3 to 5 percent of all adult patients ever enrollFor cancer: an estimated 3 to 5 percent of all adult patients ever enroll



Why is enrollment so low? Why is enrollment so low?

1.1. Patients do not know about, or understandPatients do not know about, or understand

what is offered in, clinical trials. what is offered in, clinical trials. Physician·s do not inform them (time, paper work; Pt may Physician·s do not inform them (time, paper work; Pt may

not be the ¶ideal· candidate, physician may not feel patientnot be the ¶ideal· candidate, physician may not feel patient

would be able to afford it, and more ) would be able to afford it, and more )

Janine Kresin Janine Kresin



This is not because« This is not because«

Physicians are bad people ² they simply don·t have the time orthe tools to deal with all of their patients· searches for clinicaltrials (imagine 10 patients coming to a physician with 20 trialseach ), as well patients may not be ideal for clinical trial settingsand may not be able to afford a therapy.



Other R easonsOther R easons

2.2. Patients do not meet the eligibility Patients do not meet the eligibility

requirementsrequirements



More R easonsMore R easons

3.3. Insurers will not pay for tests to show you are eligibleInsurers will not pay for tests to show you are eligible4.4. Can·t pay for therapy or to travel to clinical siteCan·t pay for therapy or to travel to clinical site5.5. Getting Getting the therapy isthe therapy is randomrandom

6.6. Therapy may NOT be effective or safe Therapy may NOT be effective or safe

anyway (~7% of CTs in phase I are approved by anyway (~7% of CTs in phase I are approved by the FD A as safe and efficacious )the FD A as safe and efficacious )

Seriously Compromising IllnessesSeriously Compromising Illnesses7.7. Too weak to travel Too weak to travel8.8. Want to be close to work, family, and friends Want to be close to work, family, and friends

*Given aforementioned reasons, many patients do not enroll.*Given aforementioned reasons, many patients do not enroll.



Access to Experimental Therapies Access to Experimental Therapies

out side out side of a Clinical Trialof a Clinical Trial



Expanded Access (EA) ProgramsExpanded Access (EA) Programs

ProgramsPrograms instituted by pharmaceuticals / drug sponsorsinstituted by pharmaceuticals / drug sponsors to offerto offertheir experimental therapy to patientstheir experimental therapy to patients n ot n ot enrolled inenrolled incorresponding clinical trials.corresponding clinical trials.

Protocol:Protocol: Pharmaceutical asks the FD A,Pharmaceutical asks the FD A,

FD A approves/denies,FD A approves/denies,

Subsequent Expanded Access program is instituted or not.Subsequent Expanded Access program is instituted or not.

How to Apply?How to Apply?

Talk to your physician, contact the pharmaceutical / therapy Talk to your physician, contact the pharmaceutical / therapy sponsor, approval / denialsponsor, approval / denial --> receive therapy in mail> receive therapy in mail



Compassionate Use (CU)/ Single PtCompassionate Use (CU)/ Single Pt

Investigational New Drug (IND)Investigational New Drug (IND) For anFor an individual patient individual patient applying to access an experimental therapy, outsideapplying to access an experimental therapy, outside

of the corresponding clinical trial / experimental study.of the corresponding clinical trial / experimental study. Protocol:Protocol:

Patient requests access to the desired therapy through a licensed physician,Patient requests access to the desired therapy through a licensed physician, Physician asks pharmaceutical,Physician asks pharmaceutical,

Pharma approves / denies; and, pending approval by pharmaPharma approves / denies; and, pending approval by pharma ---- FD A request is submitted and final FD A approval is denied or granted. ( And,FD A request is submitted and final FD A approval is denied or granted. ( And,

YES, sometimes the FD A is the one to deny you access. ) YES, sometimes the FD A is the one to deny you access. )

How to apply?How to apply? Talk with your physician, contact therapy sponsor, then FD A Talk with your physician, contact therapy sponsor, then FD A



Devil·s in the DetailsDevil·s in the Details

Four key Four key problemsproblems with Expanded Access / with Expanded Access /

Compassionate use protocolsCompassionate use protocols



This is the story of This is the story of

Joshua Thompson, ALS Joshua Thompson, ALS

Abigail Burroughs, cancer Abigail Burroughs, cancer

My grandfather, lung cancerMy grandfather, lung cancer

Many othersMany others ² ² Alzheimer·s, ALS, cancer, and more. Alzheimer·s, ALS, cancer, and more.



Problems areProblems are

1.1. Many don·t know this opportunity exists; physicians don·t tellMany don·t know this opportunity exists; physicians don·t tellthem; researchers don·t know about it and pharmas don·tthem; researchers don·t know about it and pharmas don·tbroadcast it.broadcast it.

2.2. Pharmas are worried aboutPharmas are worried about

Getting suedGetting sued

Bad press.Bad press.

As well As well

3.3. Phase II Limitations: ThePhase II Limitations: The more experimentalmore experimental the study the study , the, the

less likely it is the FD A will approve this accessless likely it is the FD A will approve this access due to moredue to moresafety concerns and less proof of efficacy safety concerns and less proof of efficacy ..

4.4. Incentives for therapy sponsors are uneconomical and do notIncentives for therapy sponsors are uneconomical and do notgive patients the full scope of opportunity.give patients the full scope of opportunity.



1. People Don·t Know 1. People Don·t Know

Some people don·t know the opportunity to access experimentalSome people don·t know the opportunity to access experimental

therapies outside of corresponding experimental studies exists.therapies outside of corresponding experimental studies exists.

Ex: my grandfather.Ex: my grandfather.



2. Pharma Worries2. Pharma Worries

Getting suedGetting sued

Bad pressBad press



3. Phase II Limitations3. Phase II Limitations

Title 21, Sec 312.34 of FD A rules and regulations implies the Title 21, Sec 312.34 of FD A rules and regulations implies theFD A is open to approving this ´experimental accessµ on anFD A is open to approving this ´experimental accessµ on anExpanded Access or Compassionate Use basis, however theExpanded Access or Compassionate Use basis, however theFD A neglects to uphold this for therapies in phase II trial andFD A neglects to uphold this for therapies in phase II trial and

prior.prior. Link toLink to FD A·s exact protocol for Treatment INDsFD A·s exact protocol for Treatment INDs

I.e., Abigail Burroughs & Joshua ThompsonI.e., Abigail Burroughs & Joshua Thompson



4. Incentives4. Incentives

A. A. Direct cost recovery Direct cost recovery

B.B. ExternalExternal--of of--trial data collectiontrial data collection



Incentive:Incentive:

DirectC

ostR

ecoveryDirectC

ostR

ecovery Through an Economist·s Eye Through an Economist·s Eye

Effective price ceiling at aEffective price ceiling at a

firm·s average total cost,firm·s average total cost,depleting any incentive fordepleting any incentive for

a sponsor to provide thisa sponsor to provide this

opportunity to patients.opportunity to patients.

Example:Example:

ProvengeProvenge



Incentive:Incentive:

ExternalExternal--of of--trial DataC

ollectiontrial DataC

ollection Results to seriously ill patient care:Results to seriously ill patient care:

a )a ) Need cliniciansNeed clinicians to deliver therapy rather than simply to deliver therapy rather than simply

physicians, as these programs are effectively a ´studyµ andphysicians, as these programs are effectively a ´studyµ and

clinical trial protocols must be followed.clinical trial protocols must be followed.b )b ) Patient can rarely combine investigational therapiesPatient can rarely combine investigational therapies with with

currently approved therapies.currently approved therapies.

Ex:Ex: JOSEPH DOUGHERTY JOSEPH DOUGHERTY



Terminal Patient Access Terminal Patient Access

All of these reasons help explain why only All of these reasons help explain why only 8 of over 8,000 open8 of over 8,000 open

clinical trials for cancer offer a corresponding Expanded Accessclinical trials for cancer offer a corresponding Expanded Access

program to terminal patientsprogram to terminal patients..

(PH ARM AS don·t care to start programs(PH ARM AS don·t care to start programs ---- no incentives andno incentives and

too much fear! )too much fear! )





R eview R eview

Four waysFour ways to access experimental therapies:to access experimental therapies:

1.1. Clinical TrialsClinical Trials

2.2. Expanded Access programsExpanded Access programs

3.3. Compassionate Use / single patient INDsCompassionate Use / single patient INDs

4.4. Emergency Use (not covered )Emergency Use (not covered )

While only 6% of therapies in phase I clinical trial reach final While only 6% of therapies in phase I clinical trial reach finalFD A approval (are proven to be safe and effective ), this isFD A approval (are proven to be safe and effective ), this isenough hope for some.enough hope for some.

Joshua Thompson Joshua Thompson



What to do? What to do?

Consult your physician aboutConsult your physician about clinical trialsclinical trials,,

compassionate usecompassionate use, and, and expanded accessexpanded access ---- if if you have a serious illness.you have a serious illness.

ClinicalTrials.gov ClinicalTrials.gov

Other CT search enginesOther CT search engines



What Are We Doing? What Are We Doing?

Bringing innovation to you at theBringing innovation to you at the fastest ratefastest rate

possiblepossible is our goal.is our goal.1.1. Community Community--based education and resource sharing based education and resource sharing

2.2. Building an interface to empower you to make a difference.Building an interface to empower you to make a difference.

3.3. Working to integrate these innovations and patient options Working to integrate these innovations and patient options

into physicians· workflow.into physicians· workflow.



R ememberR emember

Pharmas, regulators, and physicians are people tooPharmas, regulators, and physicians are people too ² ²

compassionate, yet don·t like to be cornered; are faced with theircompassionate, yet don·t like to be cornered; are faced with their

own constraints and demands on them, are sometimesown constraints and demands on them, are sometimes

desensitized to seriously ill patients, and have a limited time.desensitized to seriously ill patients, and have a limited time.

They are human, too. This isn·t a movie They are human, too. This isn·t a movie ² ² this is your and your lovedthis is your and your lovedone·s lives. Put yourself in others shoes before you act.one·s lives. Put yourself in others shoes before you act.



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Seriously Ill Patients' Access to Experimental Therapies