Attached files
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| 8-K - 8-K - DELCATH SYSTEMS, INC. | form8k.htm |
Investor Presentation
(NASDAQ: DCTH)
(NASDAQ: DCTH)
January 2014
2 DELCATH SYSTEMS, INC
Forward-looking Statements
This presentation contains forward-looking statements, within the meaning of the federal securities laws, related to future
events and future financial performance which include statements about our expectations, beliefs, plans, objectives,
intentions, goals, strategies, assumptions and other statements that are not historical facts. Forward-looking statements
are subject to known and unknown risks and uncertainties and are based on potentially inaccurate assumptions, which
could cause actual results to differ materially from expected results, performance or achievements expressed or implied
by statements made herein. Our actual results could differ materially from those anticipated in forward-looking statements
for many reasons, including, but not limited to, uncertainties relating to: stockholder approval of the proposed reverse
stock split and the Board of Directors implementation of the same, the impact of the reverse stock split on the Company's
stock price and the desired effect of a reverse stock split to regain compliance with the NASDAQ Marketplace Rules, the
Company's ability to regain compliance with the NASDAQ Marketplace Rules and maintain its listing on the NASDAQ
Capital market, the timing and results of future clinical trials including without limitation the Phase 2 and Phase 3 HCC
trials, our ability to successfully commercialize the Melphalan HDS system and the potential of the Melphalan HDS
system as a treatment for patients with primary and metastatic disease in the liver, clinical adoption, use and resulting
sales, if any, for the CHEMOSAT system in Europe, our ability to obtain reimbursement for the CHEMOSAT system in
various markets including without limitation Germany and the United Kingdom, the Company's ability to satisfy the
requirements of the FDA's Complete Response Letter and the timing of the same, approval of the Melphalan HDS system
by the US FDA, approval of the current or future Melphalan HDS system for delivery and filtration of melphalan or other
chemotherapeutic agents for various indications in the US and/or in foreign markets, actions by the FDA or other foreign
regulatory agencies, our ability to successfully enter into strategic partnership and distribution arrangements in foreign
markets and the timing and revenue, if any, of the same, uncertainties relating to the timing and results of research and
development projects, and uncertainties regarding our ability to obtain financial and other resources for any research,
development, clinical trials and commercialization activities. These factors, and others, are discussed from time to time in
our filings with the Securities and Exchange Commission including the section entitled ‘‘Risk Factors’’ in our most recent
Annual Report on Form 10-K and our Reports on Form 10-Q and Form 8-K.
events and future financial performance which include statements about our expectations, beliefs, plans, objectives,
intentions, goals, strategies, assumptions and other statements that are not historical facts. Forward-looking statements
are subject to known and unknown risks and uncertainties and are based on potentially inaccurate assumptions, which
could cause actual results to differ materially from expected results, performance or achievements expressed or implied
by statements made herein. Our actual results could differ materially from those anticipated in forward-looking statements
for many reasons, including, but not limited to, uncertainties relating to: stockholder approval of the proposed reverse
stock split and the Board of Directors implementation of the same, the impact of the reverse stock split on the Company's
stock price and the desired effect of a reverse stock split to regain compliance with the NASDAQ Marketplace Rules, the
Company's ability to regain compliance with the NASDAQ Marketplace Rules and maintain its listing on the NASDAQ
Capital market, the timing and results of future clinical trials including without limitation the Phase 2 and Phase 3 HCC
trials, our ability to successfully commercialize the Melphalan HDS system and the potential of the Melphalan HDS
system as a treatment for patients with primary and metastatic disease in the liver, clinical adoption, use and resulting
sales, if any, for the CHEMOSAT system in Europe, our ability to obtain reimbursement for the CHEMOSAT system in
various markets including without limitation Germany and the United Kingdom, the Company's ability to satisfy the
requirements of the FDA's Complete Response Letter and the timing of the same, approval of the Melphalan HDS system
by the US FDA, approval of the current or future Melphalan HDS system for delivery and filtration of melphalan or other
chemotherapeutic agents for various indications in the US and/or in foreign markets, actions by the FDA or other foreign
regulatory agencies, our ability to successfully enter into strategic partnership and distribution arrangements in foreign
markets and the timing and revenue, if any, of the same, uncertainties relating to the timing and results of research and
development projects, and uncertainties regarding our ability to obtain financial and other resources for any research,
development, clinical trials and commercialization activities. These factors, and others, are discussed from time to time in
our filings with the Securities and Exchange Commission including the section entitled ‘‘Risk Factors’’ in our most recent
Annual Report on Form 10-K and our Reports on Form 10-Q and Form 8-K.
3 DELCATH SYSTEMS, INC
Investment Thesis
§ Innovative therapy addresses an underserved liver cancer
market
market
§ Commercially available in Europe; under clinical development
in the United States
in the United States
§ Positive efficacy signal in multiple tumor types
§ Plan for 2014 initiation of Phase 2 clinical development
program in patients with unresectable Hepatocellular
Carcinoma (HCC)
program in patients with unresectable Hepatocellular
Carcinoma (HCC)
§ Seeking reimbursement in key EU markets
§ Resources to support core objectives throughout 2014
4 DELCATH SYSTEMS, INC
The Delcath Hepatic Delivery System
Veno-veno
Bypass Pump
Bypass Pump
3. Filters
2. Blood and melphalan
collected in IVC as they
exit liver via hepatic
veins
1. Melphalan
administration
directly into
Hepatic Artery
blood flow
administration
directly into
Hepatic Artery
blood flow
4. Filtered blood returned
to systemic circulation via
jugular vein
jugular vein
5 DELCATH SYSTEMS, INC
U.S. Market
Melphalan for Injection with
Delcath Hepatic Delivery System
§ Clinical development stage - proprietary
Drug/Device Combination Product Regulated
as a drug by the FDA
Drug/Device Combination Product Regulated
as a drug by the FDA
§ Intend to conduct global HCC clinical
program
program
§ Evaluating best path forward in ocular
melanoma liver metastases following FDA
Complete Response Letter (CRL) in
September 2013
melanoma liver metastases following FDA
Complete Response Letter (CRL) in
September 2013
Product Status
EU Markets
CHEMOSAT®
Hepatic Delivery System
§ Regulated as a Class IIb Medical Device
§ Indicated for the intra-hepatic
administration of melphalan hydrochloride
and subsequent filtration of the venous
blood return
administration of melphalan hydrochloride
and subsequent filtration of the venous
blood return
§ CHEMOSAT Kit supplied without
melphalan
melphalan
§ In EU, the product at market access and
clinical adoption stage
clinical adoption stage
§ Seeking reimbursements: NUB-1 in
Germany, block grant in UK
Germany, block grant in UK
6 DELCATH SYSTEMS, INC
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Positive Efficacy Signals in Multiple Liver Tumor Types
Phase 1
Unresectable
hepatic tumors
Unresectable
hepatic tumors
N=34 PHP
Phase 2
Unresectable hepatic tumors
Unresectable hepatic tumors
N=56 PHP
Phase III
Melanoma Liver Mets
Melanoma Liver Mets
N=93 44 PHP, 49 BAC
OS Follow-up
EU Prospective Registry
Phase 2 - Phase 3
Hepatocellular Carcinoma
Multi Histology
Melanoma Liver Mets
HCC
EU
Retro-
Registry
7 DELCATH SYSTEMS, INC
Clinically Differentiated Results
§ Phase 1, 2 and 3 trials produced positive results in multiple tumor types
§ Melanoma Liver Mets
§ Positive Phase 3 results in hepatic metastatic melanoma
§ n=93 (90% ocular melanoma, 10% cutaneous melanoma)
§ Neuroendocrine Tumor (NET) Liver Mets
§ mNET cohort in Phase 2 trial showed encouraging 42% objective response rate
(ORR) vs ~10% for approved targeted therapy
(ORR) vs ~10% for approved targeted therapy
§ Median overall survival of ~32 months on Intent to Treat (ITT) basis
§ Hepatocellular Carcinoma (HCC)
§ Encouraging signal in HCC cohort of Phase 2 trial
§ Colorectal Cancer (CRC) Liver Mets
§ Data from surgical Isolated Hepatic Perfusion (IHP) with melphalan indicates strong
potential in well-defined patient population with earlier stage CRC yielding ~50-60%
median response rate and median OS of 17.4-24.8 months
potential in well-defined patient population with earlier stage CRC yielding ~50-60%
median response rate and median OS of 17.4-24.8 months
8 DELCATH SYSTEMS, INC
INDEPENDENT REVIEW COMMITTEE (IRC) ASSESSMENT - UPDATED ANALYSIS (4 June 2012)
Hepatic progression-free survival (IRC)
Hazard ratio = 0.50
(95% CI 0.31-0.80)
P=0.0029
0 5 10 15 20 25 30
Months
7.0
1.7
1.0
0.8
0.6
0.4
0.2
0.0
Proportion of patients surviving
5.3 mo
Intent-to-treat population
Chemosaturation (CS-PHP)
Best alternative care (BAC)
Best alternative care (BAC)
Phase 3 Results - Primary Endpoint hPFS
CS-PHP Demonstrated 4x or 5.3 months Improvement in Primary Endpoint of hPFS
9 DELCATH SYSTEMS, INC
INVESTIGATOR ASSESSMENT - UPDATED ANALYSIS (4 June 2012)
Overall progression-free survival (investigator)
Months
5.4
1.6
1.0
0.8
0.6
0.4
0.2
0.0
Proportion of patients surviving
Hazard ratio = 0.42
(95% CI 0.27-0.64)
P<0.0001
0 5 10 15 20 25 30 35 40 45 50 55
3.8 mo
Intent-to-treat population
Chemosaturation (CS-PHP)
Best alternative care (BAC)
Best alternative care (BAC)
Phase 3 Results - Overall PFS
CS-PHP also Demonstrated a Highly Statistically Significant Improvement in Overall PFS
10 DELCATH SYSTEMS, INC
Risks associated with Melphalan HDS
§ In clinical trials using early versions of the device, the integrated safety
population of patients showed risks associated with Melphalan HDS to
include:
population of patients showed risks associated with Melphalan HDS to
include:
§ 4.1% incidence of deaths due to adverse reactions
§ 4% incidence of stroke
§ 2% reported incidence of myocardial infarction in the setting of an
incomplete cardiac risk assessment
incomplete cardiac risk assessment
§ a ≥ 70% incidence of grade 4 bone marrow suppression with a median time
of recovery of greater than 1 week
of recovery of greater than 1 week
§ 18% incidence of febrile neutropenia, along with the additive risk of hepatic
injury, severe hemorrhage, and gastrointestinal perforation
injury, severe hemorrhage, and gastrointestinal perforation
§ Deaths due to certain adverse reactions did not occur again during the
clinical trials following the adoption of related protocol amendments
clinical trials following the adoption of related protocol amendments
§ Future clinical trials will include use of the Generation Two filter and
procedure refinements intended to better control toxicities
procedure refinements intended to better control toxicities
11 DELCATH SYSTEMS, INC
FDA Complete Response Letter (CRL) on Melanoma NDA
§ Issued in September 2013
§ FDA requests include, but not limited to:
§ Well-controlled randomized trial(s) to establish the safety and
efficacy using the to-be-marketed device configuration
§ Overall survival as the primary efficacy outcome measure
§ Demonstrate clinical benefits outweigh its risks
§ Type A Meeting Held with FDA November 2013
§ Confirmed understanding of CRL device and procedure safety
requirements
requirements
§ Incorporating FDA feedback in current Phase 2 HCC trial design
§ Continuing to evaluate best path forward for ocular melanoma liver
metastases
metastases
Pursuing Phase 2 To Establish Proof of Concept in HCC,
Address FDA Safety Concerns Prior To Embarking On Pivotal Phase 3 Trials
12 DELCATH SYSTEMS, INC
HCC Rationale - U.S. & Global
§ Large Global Market
§ HCC most common primary cancer of the liver
§ ~750,000* new cases diagnosed worldwide annually
§ ~100,000 potentially suitable for treatment with
CHEMOSAT/Melphalan HDS
CHEMOSAT/Melphalan HDS
§ Liver centric disease, liver centric treatment
§ Large unmet need in first line therapy
§ Only one currently approved chemotherapy in U.S., Europe,
certain Asian markets
certain Asian markets
§ 80-90% of patients are not suitable for surgical resection
§ Focal interventions have limitations with larger tumor burden and
micro-metastases
micro-metastases
*Source: GLOBOCAN
13 DELCATH SYSTEMS, INC
Encouraging Signal in Previous P2 HCC Study with Mel/HDS
|
Subject
ID |
Age
(yr)
|
Sex
(M/F)
|
Race
|
Baseline
tumor burden (% of hepatic involveme nt) |
Number
of PHP received |
Hepatic
response/ overall
response |
hPFS
(month) |
Overall
PFS (month) |
OS
(Month)
|
|
008
|
57
|
F
|
white
|
5
|
3
|
SD/SD
|
4.37
|
4.37
|
19.88
|
|
010
|
63
|
M
|
white
|
40
|
1
|
NE/NE
|
3.35d
|
3.35d
|
3.35
|
|
011
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61
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M
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white
|
20
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4
|
SD/SD
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8.15
|
8.15
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10.12
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|
025
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61
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M
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black
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65
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3
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SD/SD
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3.45
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3.45
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5.26
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|
034
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49
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M
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white
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40
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4
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PR/PR
|
12.22
|
12.22
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20.47
|
14 DELCATH SYSTEMS, INC
§ Global Phase 2 1L - Mel/HDS - sorafenib sequential treatment of
HCC confined to the liver
HCC confined to the liver
§ Multi-center, open label trial
§ Staged trial design with early opportunity for interim
analysis/proof of concept in 2014
analysis/proof of concept in 2014
§ Objective Response Rate (CR + PR) after 2 cycles Mel/HDS
§ FDA granted orphan drug designation for Mel/HDS for HCC
§ Intend to seek partners on strength of interim Phase 2 results
§ Global Pivotal Trial in HCC - to follow Phase 2 assuming positive
results
results
Clinical Plan to establish efficacy and safety of Mel/HDS for HCC
Global Hepatocellular Carcinoma (HCC) Clinical Plan
15 DELCATH SYSTEMS, INC
§ Continued commercial market access and clinical adoption activities
in key EU countries
in key EU countries
§ Current focus on Germany and UK
§ 15 Clinical Sites treated patients in EU
§ Clinicians using CHEMOSAT for a broad range of liver metastases
§ Including: cutaneous melanoma, ocular melanoma, colorectal cancer
(CRC), gastric cancer, breast cancer, neuroendocrine tumor (NET),
hepatocellular carcinoma (HCC) and cholangiocarcinoma
(CRC), gastric cancer, breast cancer, neuroendocrine tumor (NET),
hepatocellular carcinoma (HCC) and cholangiocarcinoma
§ Intend to support Investigator Initiated Trials (IITs) to further drive
clinical adoption in the EU
clinical adoption in the EU
Expanding EU Clinical Adoption
CHEMOSAT: Expanding Clinical Use in the EU
16 DELCATH SYSTEMS, INC
CHEMOSAT: Commercial Treatments in Europe
Multiple Tumor Types Treated
Patients/Treatments
|
Year
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2012
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2013
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Total
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|
PTS
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27
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28
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55
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TX
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33
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40
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73
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2nd TX
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4
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11
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15
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3rd TX
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2
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1
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3
|
17 DELCATH SYSTEMS, INC
§ University of Heidelberg Hospital
§ Berlin Charité Hospital
§ University Medical Center Göttingen
§ Johann Wolfgang Goethe-
Universität
Universität
§ University of Bonn
§ Asklepios Clinic Bambek
§ Southampton University Hospital
§ SPIRE Southampton Hospital
§ European Institute of Oncology
§ Varese University Hospital
§ Netherlands Cancer Institute- Antoni
van Leeuwenhoek Hospital
van Leeuwenhoek Hospital
§ Cancer Institute Gustave Roussy
§ Hôpital Saint-André
§ Clinica Rotger Majorca Hospital
§ University Hospital Galway
CHEMOSAT Treatment Sites in Europe
18 DELCATH SYSTEMS, INC
2015
2013
2012
2014
EU Reimbursement Status
DRG Code
~2 years data collection
from 1st introduction
from 1st introduction
NUB Value 4 Granted
2/2013
ZE Resubmission
March 2013
NUB Decision
1 Feb 2014
ZE Application
(German Radiology Society)
ZE Denied
NUB
Submission
Submission
10/2012
NUB
Resubmission
Resubmission
October 2013
Alternative HRG
coding
coding
· Coding to cover
part of procedure
part of procedure
Interim Funding
Submissions
Submissions
· Individual funding
· National Cancer Fund
· National Care Commissioner
Block funding
· Application to fund
· 50-75 OM patients
· 15-20 CM patients
· Decision March/2014
· If approved, block funds
available 4/2014
available 4/2014
DRG Code
~2 years after
Phase 3 publication
Phase 3 publication
19 DELCATH SYSTEMS, INC
Multiple Capital Resources Available to Execute Plan
|
Cash & Cash Equivalents
|
$31.2 million at December 31, 2013
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Debt
|
None
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ATM Program
|
$44 million available at December 31, 2013
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|
Committed Equity Financing
Facility (CEFF) |
$24 million available at December 31, 2013
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Working Capital Line of Credit
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$20 million credit facility
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Shares Outstanding
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134 million (153 million fully diluted1,2) at
December 31, 2013 |
1) Fully diluted includes approximate 4 million options and 15 million warrants
2) Anticipate Feb 24, 2014 stockholder meeting seeking approval of reverse stock split to help regain NASDAQ Listing compliance
|
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2012
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2013 (Unaudited)
|
2014 Guidance
|
||||
|
|
FY
|
Q1 A
|
Q2 A
|
Q3 A
|
Q4 Est.
|
FY Est.
|
Quarterly Avg
|
|
Cash Spend Guidance
|
|
$9-12M
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$9-12M
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$7-8M
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$6-7M
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$5-6M
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Cash Spend Act./Est.
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$53M
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$11M
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$11M
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$7M
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$6M
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$35M
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Product Revenue
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$347K
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$81K
|
-
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$72K
|
$338K
|
$490K
|
|
20 DELCATH SYSTEMS, INC
Investment Thesis
§ Innovative therapy addresses an underserved liver cancer
market
market
§ Commercially available in Europe; under clinical development
in the United States
in the United States
§ Positive efficacy signal in multiple tumor types
§ Plan for 2014 initiation of Phase 2 clinical development
program in patients with unresectable Hepatocellular
Carcinoma (HCC)
program in patients with unresectable Hepatocellular
Carcinoma (HCC)
§ Seeking reimbursement in key EU markets
§ Resources to support core objectives throughout 2014
* DELCATH SYSTEMS, INC
© 2013 DELCATH SYSTEMS, INC. ALL RIGHTS RESERVED
22 DELCATH SYSTEMS, INC
APPENDIX
23 DELCATH SYSTEMS, INC
LEADERSHIP TEAM
Barbra Keck
Vice President, Controller &
Principal Accounting Officer
Principal Accounting Officer
Jennifer Simpson, PhD., M.S.N.,
C.R.N.P.
C.R.N.P.
Interim Co-President and Co-CEO
EVP, Global Head of Business
Operations
Operations
Graham G. Miao, Ph.D., M.S., MBA
Interim Co-President and Co-CEO,
EVP, Chief Financial Officer
EVP, Chief Financial Officer
Peter J. Graham
Executive Vice President,
General Counsel, Chief
Compliance Officer and Global
Human Resources
General Counsel, Chief
Compliance Officer and Global
Human Resources
John Purpura
Executive Vice President
Regulatory Affairs, Quality
Assurance
Regulatory Affairs, Quality
Assurance
Gloria Lee, M.D., Ph.D.
Executive Vice President,
Clinical & Medical Affairs
Clinical & Medical Affairs
24 DELCATH SYSTEMS, INC
Publications
• Published in 2013
o Metastatic melanoma to the liver: A contemporary and comprehensive review of
surgical, systemic, and regional therapeutic options. Agarwala SS, Eggermont
AM, O'Day S, Zager JS. Cancer. 2013 Dec 2.
surgical, systemic, and regional therapeutic options. Agarwala SS, Eggermont
AM, O'Day S, Zager JS. Cancer. 2013 Dec 2.
o Chemosaturation with percutaneous hepatic perfusion for unresectable metastatic
melanoma or sarcoma to the liver: A single institution experience. Forster MR,
Rashid OM, Perez MC, Choi J, Chaudhry T, Zager JS. J Surg Oncol. 2013 Nov 19
melanoma or sarcoma to the liver: A single institution experience. Forster MR,
Rashid OM, Perez MC, Choi J, Chaudhry T, Zager JS. J Surg Oncol. 2013 Nov 19
o Isolated hepatic perfusion for metastatic melanoma. Yamamoto M, Zager JS.
J Surg Oncol. 2013 Oct 25.
J Surg Oncol. 2013 Oct 25.
• Expected in 2014
o Phase III and Phase II Publications - In preparation
o Vogl, et al. "Chemosaturation with Percutaneous Hepatic Perfusions of Melphalan
for Hepatic Metastases: Experience from Two European Centres“ (Accepted)
for Hepatic Metastases: Experience from Two European Centres“ (Accepted)
o Ferrucci, et al. “Experience with Generation 1 Filters vs Generation 2 Filters”
(Under Review)
(Under Review)
o Alexander, et al. “Review of Percutaneous Hepatic Perfusion for Ocular Melanoma
Liver Metastases” (Submitted) to be published in American Oncology and
Hematology
Liver Metastases” (Submitted) to be published in American Oncology and
Hematology
o Chen, M. et al. “Anesthetic Management of Patients Undergoing Percutaneous
Hepatic Perfusion of Melphalan for Treatment of Metastatic Liver Cancer” (final
stages of review, hopeful winter 2014 publication)
Hepatic Perfusion of Melphalan for Treatment of Metastatic Liver Cancer” (final
stages of review, hopeful winter 2014 publication)
25 DELCATH SYSTEMS, INC
Abstracts Presented (2012-2013)
Ø Moeslein F. Chemosaturation therapy - evolution, clinical
experience and applications.
experience and applications.
Ø Deneve JL. Percutaneous hepatic perfusion for unresectable
metastatic sarcoma to the liver.
metastatic sarcoma to the liver.
Ø Wood B. Isolated liver perfusion.
Ø Zager J. Chemosaturation therapy with percutaneous hepatic
perfusions of melphalan versus standard of care in patients
with hepatic metastases from melanoma: A randomized
multicenter phase 3 study.
perfusions of melphalan versus standard of care in patients
with hepatic metastases from melanoma: A randomized
multicenter phase 3 study.
Ø Ferrucci P. Chemosaturation therapy as part of patient
management: an oncologist's perspective.
management: an oncologist's perspective.
Ø Orsi F. First European center experience with chemosaturation:
an IR's perspective.
an IR's perspective.
Ø Vogl TJ. Chemosaturation therapy: an Interventional
Radiologist's perspective on where it fits now and in the future.
Radiologist's perspective on where it fits now and in the future.
Ø Ferrucci P. Chemosaturation therapy with percutaneous
hepatic perfusion (CS-PHP) for unresectable hepatic
metastases: the European Institute of Oncology (EIO)
Experience.
hepatic perfusion (CS-PHP) for unresectable hepatic
metastases: the European Institute of Oncology (EIO)
Experience.
Ø Moeslein F. Chemosaturation with percutaneous hepatic
perfusions: vasopressor, nitroglycerin, and pre-embolization
requirements
perfusions: vasopressor, nitroglycerin, and pre-embolization
requirements
Ø Moeslein F. Chemosaturation with percutaneous hepatic
perfusions (CS-PHP): Utilization of vasopressors, nitroglycerin,
and pre-embolization
perfusions (CS-PHP): Utilization of vasopressors, nitroglycerin,
and pre-embolization
Ø Moeslein F. Chemosaturation using percutaneous hepatic perfusion: pre-
embolization of GI branches in a phase 3 clinical trial.
embolization of GI branches in a phase 3 clinical trial.
Ø Alexander HR. Percutaneous hepatic perfusion (PHP or CHEMOSAT®) with
melphalan versus best alternative care in patients with hepatic
metastases from melanoma: A post-hoc analysis of PHP-randomized vs
BAC-to-PHP crossover vs BAC-only pts.
melphalan versus best alternative care in patients with hepatic
metastases from melanoma: A post-hoc analysis of PHP-randomized vs
BAC-to-PHP crossover vs BAC-only pts.
Ø Gardner ER. Pharmacokinetic analysis of Percutaneous Hepatic Perfusion
(PHP) of melphalan in patients with hepatic metastases from melanoma.
(PHP) of melphalan in patients with hepatic metastases from melanoma.
Ø Alexander HR. Hepatic perfusion (CHEMOSAT® or CS-PHP) of melphalan
vs. best alternative care in patients with hepatic metastases from
melanoma: Update of a randomized phase 3 study.
vs. best alternative care in patients with hepatic metastases from
melanoma: Update of a randomized phase 3 study.
Ø Gardner ER. Percutaneous hepatic perfusion (CHEMOSAT® or CS-PHP) of
melphalan in patients with hepatic metastases from melanoma: Phase III
pharmacokinetic analysis
melphalan in patients with hepatic metastases from melanoma: Phase III
pharmacokinetic analysis
Ø Testori A. Chemosaturation therapy with percutaneous hepatic perfusion
(CS-PHP) for unresectable hepatic metastases: the European Institute of
Oncology (EIO) Experience
(CS-PHP) for unresectable hepatic metastases: the European Institute of
Oncology (EIO) Experience
Ø Gardner ER. Pharmacokinetic Analysis of Percutaneous Hepatic Perfusion
of Melphalan in Patients with Hepatic Metastases from Melanoma
of Melphalan in Patients with Hepatic Metastases from Melanoma
Ø Forster M. Percutaneous hepatic perfusion for unresectable melanoma or
sarcoma to the liver: a single institution experience.
sarcoma to the liver: a single institution experience.
Ø Testori A. Chemosaturation therapy with percutaneous hepatic perfusion
for unresectable liver metastases: the European Institute of Oncology
(EIO) experience.
for unresectable liver metastases: the European Institute of Oncology
(EIO) experience.
26 DELCATH SYSTEMS, INC
Delcath ODAC Presentation - Summary
Full Delcath and FDA ODAC Briefing Materials Available at
http://www.delcath.com/clinical-research/clinical-bibliography/
Procedure-related deaths
§ Five deaths (4.1%) in the Phase 2 and Phase 3 clinical trials were
considered treatment-related and resulted from adverse events
considered treatment-related and resulted from adverse events
§ Four deaths in Phase 3 trial; one in Phase 2 trial
§ Treatment-related deaths in the pooled percutaneous hepatic perfusion (PHP)
population were a consequence of either the PHP procedure, or the direct local
effects of melphalan during the procedure, or both
population were a consequence of either the PHP procedure, or the direct local
effects of melphalan during the procedure, or both
§ Of which, two deaths due to gastric ulceration/perforation:
§ A death due to upper GI hemorrhage in the Phase 2 trial in male patient with
pancreatic neuroendocrine tumor (NET) who had a prior surgical (Whipple’s)
procedure and consequent abnormal architecture of the upper GI tract, its
vasculature, and biliary tree. Patient died on Day 74 after melphalan/PHP
treatment and an autopsy revealed a ruptured right hepatic artery as the primary
cause of death
pancreatic neuroendocrine tumor (NET) who had a prior surgical (Whipple’s)
procedure and consequent abnormal architecture of the upper GI tract, its
vasculature, and biliary tree. Patient died on Day 74 after melphalan/PHP
treatment and an autopsy revealed a ruptured right hepatic artery as the primary
cause of death
§ A death due to gastric perforation in a male patient in the Phase 3 trial who
crossed over to melphalan/PHP treatment after hepatic progression on best
alternative care (BAC). Patient went into cardiopulmonary arrest and died during a
laparotomy on Day 18 after his second treatment cycle
crossed over to melphalan/PHP treatment after hepatic progression on best
alternative care (BAC). Patient went into cardiopulmonary arrest and died during a
laparotomy on Day 18 after his second treatment cycle
27 DELCATH SYSTEMS, INC
Delcath ODAC Presentation - Summary
Full Delcath and FDA ODAC Briefing Materials Available at
http://www.delcath.com/clinical-research/clinical-bibliography/
§ One death due to hepatic failure:
§ A death due to hepatic failure occurred in male patient in the
Phase 3 trial during the first cycle of melphalan/PHP treatment.
Following melphalan/PHP treatment, this patient experienced fluid
overload, myelosuppression, and hepatorenal syndrome.
Phase 3 trial during the first cycle of melphalan/PHP treatment.
Following melphalan/PHP treatment, this patient experienced fluid
overload, myelosuppression, and hepatorenal syndrome.
§ An autopsy revealed that this patient’s death was related to
underlying disease burden as the tumor burden in his liver was
greater than 90%
underlying disease burden as the tumor burden in his liver was
greater than 90%
§ Two deaths were attributable to complications of neutropenia, beyond
the first cycle of treatment
the first cycle of treatment
§ One patient died of streptococcal sepsis
§ One died of neutropenic complications
28 DELCATH SYSTEMS, INC
Delcath ODAC Presentation - Summary
Full Delcath and FDA ODAC Briefing Materials Available at
http://www.delcath.com/clinical-research/clinical-bibliography/
§ Prophylactic growth factor support, which is used to treat neutropenia,
was not protocol specified and rarely used during P2 and P3 melanoma
trials
was not protocol specified and rarely used during P2 and P3 melanoma
trials
§ In patients who have been treated with the Generation Two system,
both commercially in Europe and in the US under the Expanded Access
Program and compassionate use, we have not seen complicated
neutropenia to date
both commercially in Europe and in the US under the Expanded Access
Program and compassionate use, we have not seen complicated
neutropenia to date
§ Myelosuppression is always a risk with chemotherapy, Delcath has
recommended following the American Society of Clinical Oncology
(ASCO) guidelines for the use of growth factors to mitigate the incidence
of complicated neutropenia
recommended following the American Society of Clinical Oncology
(ASCO) guidelines for the use of growth factors to mitigate the incidence
of complicated neutropenia
29 DELCATH SYSTEMS, INC
FDA ODAC Presentation - Summary
Full Delcath and FDA ODAC Briefing Materials Available at
http://www.delcath.com/clinical-research/clinical-bibliography/
FDA disagreed with Delcath assessment and added three additional
deaths, for a total of a 7% percent death rate, in the Phase 2 and Phase
3 programs:
deaths, for a total of a 7% percent death rate, in the Phase 2 and Phase
3 programs:
§ Two deaths related to hepatic failure
§ One death related to myelosuppression
§ Upon being advised of the FDA’s assessment of these deaths, the
Company requested that the cases be re-reviewed by the treating
principal investigators
Company requested that the cases be re-reviewed by the treating
principal investigators
§ After this review, the treating principal investigators continue to be
convinced that these patients died of disease progression, and the
Company believes that the three additional deaths the FDA attributed to
the procedure were unrelated to treatment
convinced that these patients died of disease progression, and the
Company believes that the three additional deaths the FDA attributed to
the procedure were unrelated to treatment
In its ODAC presentation, FDA also cited concerns about periods of
hypotension (low blood pressure) during the procedure, length of
hospital stay, as well as risks of stroke, heart attack, renal failure, and
bone marrow suppression.
hypotension (low blood pressure) during the procedure, length of
hospital stay, as well as risks of stroke, heart attack, renal failure, and
bone marrow suppression.
30 DELCATH SYSTEMS, INC
EU REIMBURSEMENT - Acronym Definition
Germany
ZE - (Zusatzentgeld) form of additional compensation for approved treatments which are not
sufficiently compensated by the existing DRG codes in place.
sufficiently compensated by the existing DRG codes in place.
NUB - (Neue Untersuchungs- und Behandlungsmethoden) provides reimbursement between the
gap of availability of new procedures and correct coding in the DRG system.
gap of availability of new procedures and correct coding in the DRG system.
InEK - (Institut für das Entgeldsystem im Krankenhaus) Institute for the German hospital
remuneration system.
remuneration system.
Calculation Hospitals - hospitals which collect and submit procedure costs to InEK
UK
HRG - (Health Resource Group) used by the National Health System as a unified set of codes
grouping patient events which incur a similar amount of resources. Used by the “Payment by
Result” system to obtain reimbursement for concluded patient episodes/treatments.
grouping patient events which incur a similar amount of resources. Used by the “Payment by
Result” system to obtain reimbursement for concluded patient episodes/treatments.
NICE - (National Institute for Clinical Excellence) body which reviews and publishes guidance on
new treatment methods. Guidance is internationally highly recognised.
new treatment methods. Guidance is internationally highly recognised.
Other
DRG - (Diagnosis Related Group) coding system classifying patient treatments and used to obtain
reimbursement for procedures carried out (same as HRG for UK)
reimbursement for procedures carried out (same as HRG for UK)