Single Patient Use of Investigational Anticancer Agents: An Industry Perspective Gerard T....
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Transcript of Single Patient Use of Investigational Anticancer Agents: An Industry Perspective Gerard T....
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