paul goldfarb, m.d. grand rounds 2005. inovio’s proprietary medpulser ® system generator: capable...

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.


Patient 002: 4 weeks post EPT

The tumor has a definitive margin after 4 weeks.


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.


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


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


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


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.


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.

paul goldfarb, m.d. grand rounds 2005. inovio’s proprietary medpulser ® system generator: capable...

Documents