Grand Rounds 2005. Paul Goldfarb, M.D . Inovio’s Proprietary Medpulser ® System. Generator: • Capable of several thousand treatments • Generates square wave DC current. Applicator: • One per patient/treatment
Paul Goldfarb, M.D.
• Capable of several thousand treatments
•Generatessquare wave DC current
• One per patient/treatment
• Usage restricted by smart-chip
• Sizeable gross margin
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.
Adjustable angle applicators
allow the angle of the needle probe to applicator handle
to be infinitely adjusted from 0º to 90º, permitting the physician to treat tumors on the lateral aspect of organs.
(Cell returns to original state)
Electroporation applies brief electrical pulses, inducing pores to open in the cell membrane and dramatically increasing uptake of useful drugs, genes & DNA vaccines
A simple and effective system of delivering drugs or genes into cells
Electroporation Therapy (EPT)
drug enters cells
Very effective treatment requiring low level of technical skills
Lewis lung carcinoma
non-small cell lung
basal cell carcinoma
squamous cell carcinoma
oral, head and neck
EPT is efficacious across tumor types
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.
Phase II, Recurrent Late Stage H&N Tumors: N.A. and Europe
Bleo & EPT
Tumors Patients CR% PR%
37 25 0 3
Tumors Patients CR% PR% OR%
20 17 30 25 55
31 25 19 39 58
18 12 28 28 56
N. America IN. America II
69 54 26% 32% 57%
Market Seeding, Newly Diagnosed H&N Tumors: Europe
CR = Complete Response : Tumor shrinkage of 100%
PR = Partial Response : Tumor shrinkage of 50% or greater
OR = Objective Response : Clinical Response +
NED = No Evidence of Disease at treatment site on histological examination 4 weeks post treatment
ED = Evidence of Disease
Tumors Patients NED ED
20 20 16 4
Patients had a complete response rate of 80%
Excellent response rate in newly diagnosed H&N cancer patients
• Equivalent disease control
• Better tissue preservation
• Better function preservation
• Less cost
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
• 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
• 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.
•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.