paul goldfarb, m.d. grand rounds 2005. inovio’s proprietary medpulser ® system generator: capable...
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Paul Goldfarb, M.D.
Grand Rounds 2005
Inovio’s Proprietary Medpulser® SystemInovio’s Proprietary Medpulser® System
Generator:• Capable of several
thousand treatments
• Generates square wave DC current
Applicator:• One per patient/treatment• Usage restricted by
smart-chip
• Sizeable gross margin
Family of ApplicatorsFamily of Applicators
Adjustable angle applicatorsallow the angle of the needle probe to applicator handleto be infinitely adjusted from 0º to 90º, permitting the physician to treat tumors on the lateral aspect of organs.
Adjustable length applicators utilize their needle shield to adjust needle length by twist clicking into stops set from 0 to 3cm in 0.5cm increments.
Electroporation applies brief electrical pulses, inducing pores to open in the cell membrane and dramatically increasing uptake of useful drugs, genes & DNA vaccines
Therapeutic Platform Based on ElectroporationTherapeutic Platform Based on Electroporation
Cell MembraneBefore Pulse
Cell MembraneDuring Pulse
Cell MembraneAfter Pulse
(Cell returns to original state)
A simple and effective system of delivering drugs or genes into cells
ElectroporationDC
Cancer Therapy Procedure Utilizing EPTCancer Therapy Procedure Utilizing EPT
Very effective treatment requiring low level of technical skills
DC
Electroporation
Cell Poration, drug enters cells
Injection ofBleomycin
Pulsing theTumor with
applicator
Cells ResealAnd Die
Drug SurroundsTumor Cells
Electroporation Therapy (EPT)
EPT Pre-clinical & Clinical ExperienceEPT Pre-clinical & Clinical Experience
humanin vitro in vivo
ovarianendometrial
prostatehepaticellular carcinomaLewis lung carcinomanon-small cell lungfibrosarcomaglioma
basal cell carcinomamelanomaKaposi’s sarcomaadenocarcinomasquamous cell carcinomaoral, head and neckpancreaticliver
Tumor Type
EPT is efficacious across tumor types
Electroporation Therapy in Head and Neck CancerElectroporation Therapy in Head and Neck Cancer
Patient 002: lateral tongue cancer
The tumor is injected with Bleomycin.
Patient 002: EPT
Electroporation Therapy (EPT) is applied with the applicator.
Electroporation Therapy in Head and Neck CancerElectroporation Therapy in Head and Neck Cancer
Patient 002: 4 weeks post EPT
The tumor has a definitive margin after 4 weeks.
Electroporation Therapy in Head and Neck CancerElectroporation Therapy in Head and Neck Cancer
Patients had a complete response rate of 80%
Head & Neck Cancer Clinical DataHead & Neck Cancer Clinical Data
Phase II, Recurrent Late Stage H&N Tumors: N.A. and Europe
Market Seeding, Newly Diagnosed H&N Tumors: EuropeCR =Complete Response : Tumor shrinkage of 100%PR =Partial Response : Tumor shrinkage of 50%
or greaterOR = Objective Response : Clinical Response +
Partial ResponseNED = No Evidence of Disease at treatment site on
histological examination 4 weeks post treatmentED =Evidence of Disease
Total 69 54 26% 32% 57%
Bleo Only
Tumors Patients CR% PR%
37 25 0 3N. America I
N. America II
Europe
Tumors Patients CR% PR% OR%
20 17 30 25 55
31 25 19 39 58
18 12 28 28 56
Bleo & EPT
Tumors Patients NED ED
20 20 16 4 Europe
Excellent response rate in newly diagnosed H&N cancer patients
EPT Compared to SurgeryEPT Compared to Surgery
• Equivalent disease control
• Better tissue preservation
• Better function preservation
• Less cost
Inovio Biomedical CorporationInovio Biomedical Corporation
Our Perception:A NOVEL ABLATION SYSTEM THAT USES A
WELL CHARACTERIZED DRUG IN A PREVIOUSLY APPROVED ROUTE OF ADMINISTRATION TO ABLATE MALIGNANT TISSUE AND SPARE NON-MALIGNANT TISSUES IN CONJUNCTION WITH A DEVICE THAT ADMINISTERS BRIEF LOCALIZED ELECTRIC PULSES.
Our Regulatory Pathway as defined
by our RFD:A COMBINATION PRODUCT WITH PRIMARY
REVIEW BY CDER AND CONSULTATIVE REVIEW BY CDRH WITH A RECOMMENDATION TO CONSIDER 510-K SUBMISSION FOR THE DEVICE AT TIME OF REVIEW.
Inovio Biomedical CorporationInovio Biomedical Corporation
Original Phase III study design:
A standard survival based study in patients with end stage disease where all received systemic therapy and the study group received EPT. The primary endpoint was survival
Issues:
• A local therapy has no benefit if the total tumor burden is not addressed by the intervention.
• There is no clinical benefit [survival] to local therapy use in patients with end stage disease and this therapy would not be offered to patients in this clinical setting
Inovio Biomedical CorporationInovio Biomedical Corporation
Current Phase III study design:
• A study comparing the efficacy of EPT to surgery in patients with localized recurrent disease or second primary disease
• The endpoint is enhanced preservation of function and appearance. Survival and
local control will be no worse with EPT
Inovio Biomedical CorporationInovio Biomedical Corporation
Bleomycin issues:
• A well characterized generic drug
• A Class 1 generic drug for parenteral administration
• The device acts with a class of drugs and not a “specific drug”
• Genetronics is not the MA holder for Bleomycin & will not bring the drug into commerce
• No interest on the part of current license holders to relabel the drug
Inovio Biomedical CorporationInovio Biomedical Corporation
Resolution developed with the FDA:
• The label, included with each disposable applicator, will incorporate all relevant information regarding the use of the drug Bleomycin when used as part of an EPT
procedure
• Genetronics will monitor the available formulations of bleomycin on a routine
basis to ensure continued constancy of formulation. This is already assured by the drug classification
• The final approval will be through a PMA granted by CDRH with a collaborative
review by CDER.
Inovio Biomedical CorporationInovio Biomedical Corporation
Implications:
• New indications may not require relabeling of the drug and will be reflected in changes to the device label.
• Once initial safety issues related to Bleomycin have been reviewed by CDER, future efficacy assessments of this ablation technology might
be reviewed by CDRH and approved as supplements to a PMA.
• THIS MODEL PROVIDES A INOVATIVE, FLEXIBLE, PATHWAY TO REVIEW AND APPROVE DRUG- DEVICE COMBINATION PRODUCTS THAT USE
CERTAIN GENERIC DRUGS.