Single Patient Use of Single Patient Use of Investigational Anticancer Investigational Anticancer

Agents:Agents:

An Industry PerspectiveAn Industry Perspective

Gerard T. Kennealey, MDGerard T. Kennealey, MD

Vice President, Clinical Research, OncologyVice President, Clinical Research, Oncology

AstraZeneca PharmaceuticalsAstraZeneca Pharmaceuticals

December 14, 2000December 14, 2000

Rising Public Expectations Make Rising Public Expectations Make Earlier Access NecessaryEarlier Access Necessary

Patients are better informed than ever before:Patients are better informed than ever before:

Worldwide web Worldwide web Patient advocacy groups Patient advocacy groups Media coverage (health and medicine, Media coverage (health and medicine,

including cancer, is the single most covered including cancer, is the single most covered issue in the general media.)issue in the general media.)

Single Patient INDs Provide Needed Single Patient INDs Provide Needed Access to Promising Experimental Access to Promising Experimental

Anticancer Compounds:Anticancer Compounds:

Usually initiated near NDA submissionUsually initiated near NDA submission Extremely low prevalence diseases where Extremely low prevalence diseases where

there may no other therapeutic optionthere may no other therapeutic option Unresponsive tumorsUnresponsive tumors Responsive tumors that have exhausted all Responsive tumors that have exhausted all

standard therapiesstandard therapies

Initiating the Single Patient INDInitiating the Single Patient IND

Substantial activitySubstantial activity Safety data sufficient for filingSafety data sufficient for filing Standard therapy exhaustedStandard therapy exhausted Positive risk benefit ratioPositive risk benefit ratio

Single patient INDs are a useful tool in meeting patients’ needs:

Additional Treatment Additional Treatment Approaches Are NeededApproaches Are Needed

Patients with more common tumors are Patients with more common tumors are exhausting currently available approved and exhausting currently available approved and experimental treatment optionsexperimental treatment options

The sheer number of patients who meet this The sheer number of patients who meet this description requires a more efficient means description requires a more efficient means of meeting their legitimate medical needsof meeting their legitimate medical needs

AstraZeneca ExperienceAstraZeneca Experience ZD1839 (IressaZD1839 (Iressa™)™)

EGFR tyrosine kinase inhibitorEGFR tyrosine kinase inhibitor Orally bioavailable, once daily dosingOrally bioavailable, once daily dosing Phase I clinical trials begun May 1998Phase I clinical trials begun May 1998 AACR presentations May 2000, AACR presentations May 2000,

including plenary session showed activityincluding plenary session showed activity AACR and institutional media focusAACR and institutional media focus

The drug unexpectedly shrank tumors and prolonged survival in a first stage study, where efficacy is rarely shown.

Targeted therapies offer best hope for beating cancer

Initial Plan: Initial Plan: Initiate Phase III TrialsInitiate Phase III Trials

Since AACR, AstraZeneca’s information Since AACR, AstraZeneca’s information center and various patient and professional center and various patient and professional groups have received more than 7500 groups have received more than 7500 inquires about the compoundinquires about the compound

Calls from elected representatives, Calls from elected representatives, celebrities, and other high profile celebrities, and other high profile individuals expecting “instant access” were individuals expecting “instant access” were received every weekreceived every week

Expanded Access Program (EAP)Expanded Access Program (EAP)Previous PrecedentsPrevious Precedents

Treatment IND, parallel track, and Treatment IND, parallel track, and compassionate use programs for HIV/AIDS compassionate use programs for HIV/AIDS drugs, e.g., ddIdrugs, e.g., ddI

The first such Expanded Access Programs The first such Expanded Access Programs in oncology, including Herceptin and in oncology, including Herceptin and STI 571STI 571

Principles: Iressa Expanded Principles: Iressa Expanded Access Program (EAP)Access Program (EAP)

Driven by clinical data in ~300 patients Driven by clinical data in ~300 patients (NSCLC)(NSCLC)

Patient safety is primary concernPatient safety is primary concern Equal access throughout the worldEqual access throughout the world No special cases – backing of senior No special cases – backing of senior

managementmanagement Drug supply a potential issueDrug supply a potential issue No interference with registration programNo interference with registration program

Registration Is The Best Registration Is The Best Route To Expanded AccessRoute To Expanded Access

PatientsPatients PhysiciansPhysicians FDAFDA Pharmaceutical companyPharmaceutical company

The Iressa (EAP): Initial StepsThe Iressa (EAP): Initial Steps

Create dedicated EAP TeamCreate dedicated EAP Team Involve FDA Oncologic Drugs Division Involve FDA Oncologic Drugs Division

and Cancer Liaison Officeand Cancer Liaison Office Inform and collaborate with patient Inform and collaborate with patient

advocacy groups eg. ALCASEadvocacy groups eg. ALCASE Identify experienced CROIdentify experienced CRO Collaborate with National Organization Collaborate with National Organization

for Rare Disorders (NORD)for Rare Disorders (NORD)

Iressa EAP ProtocolIressa EAP Protocol

Restricted to patients with NSCLCRestricted to patients with NSCLC Disease that failed to respond to or relapsed Disease that failed to respond to or relapsed

on standard therapy on standard therapy No concomitant therapy for tumorNo concomitant therapy for tumor Not a candidate for registration trialsNot a candidate for registration trials Adequate general healthAdequate general health Informed written consentInformed written consent

EAP ChallengesEAP Challenges

Create effective communication pathwaysCreate effective communication pathways Create one informed consent document Create one informed consent document

acceptable to all acceptable to all Determine what data must be collected, Determine what data must be collected,

recognizing that safety data allows for only recognizing that safety data allows for only minimal safety signalsminimal safety signals

EACH IS A BARRIER TO EACH IS A BARRIER TO CORPORATE PARTICIPATIONCORPORATE PARTICIPATION

EAP ConcernsEAP Concerns

Potential for impact on registration trialsPotential for impact on registration trials Potential impact on submissionPotential impact on submission Adequacy of drug supply in view of rapidly Adequacy of drug supply in view of rapidly

expanding clinical trial programsexpanding clinical trial programs Demand created by the mediaDemand created by the media Insuring equity Insuring equity Other tumor typesOther tumor types

EAP OpportunitiesEAP Opportunities

Focus corporate talent, energy, and resources Focus corporate talent, energy, and resources on a promising compound beyond on a promising compound beyond registration trialsregistration trials

Develop productive ties with partner groups, Develop productive ties with partner groups, e.g., FDA, patient and professionalse.g., FDA, patient and professionals

Potential for additional safety data at time of Potential for additional safety data at time of approval and launchapproval and launch

Reinforce commitment to timely, well Reinforce commitment to timely, well controlled clinical trialscontrolled clinical trials

Implications for the FutureImplications for the Future

Cancer drug development now operates in Cancer drug development now operates in the public eyethe public eye

An Expanded Access Protocol should be An Expanded Access Protocol should be considered to meet patient needs, considered to meet patient needs, particularly those with advanced diseaseparticularly those with advanced disease

Successful programs require commitment Successful programs require commitment from all parties involvedfrom all parties involved

FDA Guidance NeededFDA Guidance Needed

To ensure appropriate understanding, FDA To ensure appropriate understanding, FDA may wish to offer guidance on these may wish to offer guidance on these unresolved issues:unresolved issues:

The role of these data in NDA filingsThe role of these data in NDA filings Potential opportunity for early registrationPotential opportunity for early registration

Thank YouThank You 150+ patients enrolled in this program150+ patients enrolled in this program AstraZeneca EAP TeamAstraZeneca EAP Team National Organization for Rare DisordersNational Organization for Rare Disorders Patient Advocacy GroupsPatient Advocacy Groups Patty Delaney & the Cancer Liaison OfficePatty Delaney & the Cancer Liaison Office Oncologic Drugs DivisionOncologic Drugs Division Mark Krueger & Associates, IncMark Krueger & Associates, Inc