UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(D) OF THE
SECURITIES EXCHANGE ACT OF 1934
Date of report (Date of earliest event reported): October 17, 2013
DELCATH SYSTEMS, INC.
(Exact name of registrant as specified in its charter)
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Delaware
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001-16133
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06-1245881
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(State or Other Jurisdiction
of Incorporation)
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(Commission File Number)
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(IRS Employer
Identification Number)
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566 Queensbury Avenue, Queensbury, New York, 12804
(Address of principal executive offices, including zip code)
(518) 743-8892
(Registrant’s telephone number, including area code)
NONE
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
[ ] Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
[ ] Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
[ ] Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
[ ] Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Item 7.01. Regulation FD Disclosure.
A copy of Delcath Systems, Inc.’s updated investor presentation slides that the Company intends to use effective immediately is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated into this Item 7.01 by reference.
The information disclosed under this Item 7.01, including Exhibit 99.1 hereto, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, nor shall it be incorporated by reference into any registration statement or other document pursuant to the Securities Act of 1933, as amended, except as expressly set forth in such filing.
Item 9.01. Financial Statements and Exhibits.
The following exhibit is filed herewith:
(d) Exhibits.
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Exhibit No.
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Description
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99.1
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Delcath Systems, Inc. Investor Presentation Slides
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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DELCATH SYSTEMS, INC.
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Dated: October 17, 2013
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By:
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/s/ Barbra C. Keck
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Name:
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Barbra C. Keck
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Title:
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Vice President, Controller & Principal Accounting Officer
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EXHIBIT INDEX
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Exhibit No.
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Description
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99.1
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Delcath Systems, Inc. Investor Presentation Slides
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Exhibit 9.1
Investor Presentation
(NASDAQ: DCTH)
(NASDAQ: DCTH)
October 2013
2 DELCATH SYSTEMS, INC
Forward-looking Statements
This presentation contains forward-looking statements, within the meaning of 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: efficiencies and reduction in cash utilization
achieved through September 2013 staff reductions, the leadership transition plan and its impact on the Company, the
Company's ability to satisfy the requirements of the FDA's Complete Response Letter and provide the same in a timely
manner, clinical adoption, use and resulting sales, if any, for the CHEMOSAT system to deliver and filter melphalan in
Europe, our ability to successfully commercialize the chemosaturation system and the potential of the chemosaturation
system as a treatment for patients with primary and metastatic disease in the liver, our ability to obtain reimbursement for
the CHEMOSAT system in various markets, the timing and results of future clinical trials including without limitation the
HCC trials, approval of the current or future chemosaturation system for delivery and filtration of melphalan, doxorubicin
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 including Australia and key Asian markets and 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 overall
economic conditions and other factors described 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: efficiencies and reduction in cash utilization
achieved through September 2013 staff reductions, the leadership transition plan and its impact on the Company, the
Company's ability to satisfy the requirements of the FDA's Complete Response Letter and provide the same in a timely
manner, clinical adoption, use and resulting sales, if any, for the CHEMOSAT system to deliver and filter melphalan in
Europe, our ability to successfully commercialize the chemosaturation system and the potential of the chemosaturation
system as a treatment for patients with primary and metastatic disease in the liver, our ability to obtain reimbursement for
the CHEMOSAT system in various markets, the timing and results of future clinical trials including without limitation the
HCC trials, approval of the current or future chemosaturation system for delivery and filtration of melphalan, doxorubicin
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 including Australia and key Asian markets and 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 overall
economic conditions and other factors described 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
§ Liver cancer therapy company
§ Innovative Delcath Hepatic Delivery System (HDS) in
combination with high dose well-established chemotherapeutic
drug Melphalan to address an underserved liver cancer market
combination with high dose well-established chemotherapeutic
drug Melphalan to address an underserved liver cancer market
§ Clinically proven therapeutic concept for liver cancers
§ Positive efficacy signal in multiple tumor types
§ Seeking compelling reimbursement in key EU markets
§ Intend to initiate Phase 2 clinical development program in
patients with unresectable Hepatocellular Carcinoma (HCC)
patients with unresectable Hepatocellular Carcinoma (HCC)
§ Manageable cash spend to support core objectives
4 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 505(b)(2) NDA by
Regulated as a drug 505(b)(2) NDA by
the FDA
§ FDA Complete Response Letter (CRL) in
September, 2013 to NDA for indication of
unresectable ocular melanoma liver
metastasis
§ Type A meeting requested to seek
guidance on additional requirements for
OcuMel program
§ Intend to conduct global HCC clinical
program
Product Status
Ex U.S. Markets
CHEMOSAT®
Hepatic Delivery System
§ Regulated as a Class IIb Medical
Device
§ Indicated for the intra-hepatic of
administration of melphalan
hydrochloride and subsequent
filtration of the venous blood return
§ CHEMOSAT Kit supplied without
melphalan
§ In EU, the product at market access
and clinical adoption stage
§ Seeking reimbursements: NUB-1 in
Germany, block grant in UK
5 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
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
6 DELCATH SYSTEMS, INC
|
2001
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2002
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2003
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2004
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2005
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2006
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2007
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2008
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2009
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2010
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2011
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2012
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2013
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2014
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2015
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2016
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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
Retro-
Registry
EU Prospective Registry
Phase 2 – Phase 3
Hepatocellular Carcinoma
Multi Histology
Melanoma Liver Mets
HCC
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
§ Safety profiles consistent with pivotal US Phase 3 melanoma trial
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
0 5 10 15 20 25 30
Months
7.0
1.7
1.0
1.0
0.8
0.8
0.6
0.6
0.4
0.4
0.2
0.2
0.0
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
1.0
0.8
0.8
0.6
0.6
0.4
0.4
0.2
0.2
0.0
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
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 the CHEMOSAT/MELPHALAN HDS Procedure
§ In clinical trials using early versions of the device, the integrated safety
population of patients showed risks associated with the MELPHALAN
HDS procedure:
population of patients showed risks associated with the MELPHALAN
HDS procedure:
§ 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 to better control toxicities
procedure refinements to better control toxicities
11 DELCATH SYSTEMS, INC
FDA Complete Response Letter (CRL) on Melanoma NDA
§ Issued in September, 2013
§ Among FDA requests
§ Well-controlled randomized trial(s) to establish the safety and efficacy
using the to-be-marketed device configuration
using the to-be-marketed device configuration
§ Overall survival as the primary efficacy outcome measure
§ Demonstrate clinical benefits outweigh its risks
§ Company evaluating the other requirements contained in the letter,
and will review potential regulatory paths forward with the FDA.
and will review potential regulatory paths forward with the FDA.
§ Type A Meeting Requested
Ocular Melanoma Liver Metastases Program pending
outcome of further discussion with the FDA
12 DELCATH SYSTEMS, INC
HCC Rationale – U.S. & Global
*Source: GLOBOCAN
13 DELCATH SYSTEMS, INC
Encouraging Signal in Previous P2 HCC Study with Mel/HDS
|
Subject
ID |
Age
(yr)
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Sex
(M/F)
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Race
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Baseline
tumor burden (% of hepatic involveme nt) |
Number
of PHP received |
Hepatic
response/ overall
response |
hPFS
(month) |
Overall
PFS (month) |
OS
(Month)
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008
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57
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F
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white
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5
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3
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SD/SD
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4.37
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4.37
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19.88
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010
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63
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M
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white
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40
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1
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NE/NE
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3.35d
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3.35d
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3.35
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011
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61
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M
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white
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20
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4
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SD/SD
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8.15
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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
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12.22
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12.22
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20.47
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14 DELCATH SYSTEMS, INC
§ Global Phase 2 – Mel/HDS – sorafenib sequential treatment of HCC
confined to the liver
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
§ Intend to seek partners on strength of interim Phase 2 analysis
§ Global Phase 3 - first line HCC
§ Intend to conduct following Phase 2 assuming positive results
Clinical Plan to establish efficacy and safety of Mel/HDS for HCC
Global Hepatocellular Carcinoma (HCC) Clinical Plan
15 DELCATH SYSTEMS, INC
CHEMOSAT: Expanding Clinical Use in the EU
§ Continued commercial market access and clinical adoption activities
in key EU countries
in key EU countries
§ Current focus on Germany, UK, Italy
§ 12 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
cancer (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 EU markets including DE, UK, IT, NL, FR, SP
clinical adoption in EU markets including DE, UK, IT, NL, FR, SP
16 DELCATH SYSTEMS, INC
CHEMOSAT: Multiple Tumor Types Treated in Europe
17 DELCATH SYSTEMS, INC
CHEMOSAT Treatment Sites in Europe
§ Milan, Italy – European Institute of Oncology
§ Frankfurt, Germany – Johann Wolfgang Goethe-Universität
§ Villejuif, France – Cancer Institute Gustave Roussy
§ Bordeaux, France – Hôpital Saint-André
§ Galway, Ireland – University Hospital Galway
§ Southampton, United Kingdom – Southampton University Hospital
§ Göttingen, Germany – University Medical Center Göttingen
§ Varese, Italy – Varese University Hospital
§ Amsterdam, The Netherlands – Netherlands Cancer Institute- Antoni van
Leeuwenhoek Hospital
Leeuwenhoek Hospital
§ Heidelberg, Germany – University of Heidelberg Hospital
§ Berlin, Germany – Berlin Charité Hospital
§ Palma, Spain – Majorca Hospital
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 90 patients
· Decision Feb/2014
· Following approval block funds
available 4/2014
available 4/2014
DRG Code
~2 years after
Phase 3 publication
Phase 3 publication
Existing DRG code utilized by
Hospital Administration
Hospital Administration
· Covers 50% of procedure cost
Top-Up Payment Submitted
· Regional supplemental payment
· Hospitals close gaps
Regional Government decision on top
up payments
up payments
· (Lombardy obtained approval)
DRG Code
~2 years after
Phase 3 publication
Phase 3 publication
19 DELCATH SYSTEMS, INC
Multiple Capital Resources Available to Execute Plan
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Cash & Cash Equivalents
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~ $28 million at September 30, 2013
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Debt
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None
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ATM Program
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~ $47 million at September 30, 2013
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Committed Equity Financing
Facility (CEFF) |
~ $24 million at September 30, 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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~103 million (~113 million fully diluted1) at
September 30, 2013 |
1) Fully diluted includes an additional 4.7 million options and 5.4 million warrants
20 DELCATH SYSTEMS, INC
Significantly Reducing Operating Costs
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Q1 2013 Act
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$11.3 million
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Q2 2013 Act
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$10.5 million
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Projected quarterly cash spend*:
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Q3 2013 Proj
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$7-$8 million
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Q4 2013 Proj
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$6-$7 million
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Quarterly average 2014 Proj
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$5-$6 million
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Quarterly Cash Utilization:
* Based on current projection, subject to change
21 DELCATH SYSTEMS, INC
Investment Thesis
§ Liver cancer therapy company
§ Innovative Delcath Hepatic Delivery System in combination
with high dose well-established chemotherapeutic drug
Melphalan to address an underserved liver cancer market
with high dose well-established chemotherapeutic drug
Melphalan to address an underserved liver cancer market
§ Clinically proven therapeutic concept for liver cancers
§ Positive efficacy signal in multiple tumor types
§ Seeking compelling reimbursement in key EU markets
§ Intend to initiate Phase 2 clinical development program in
patients with unresectable Hepatocellular Carcinoma (HCC)
patients with unresectable Hepatocellular Carcinoma (HCC)
§ Manageable cash spend to support core objectives
* DELCATH SYSTEMS, INC
© 2013 DELCATH SYSTEMS, INC. ALL RIGHTS RESERVED
23 DELCATH SYSTEMS, INC
APPENDIX
24 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
25 DELCATH SYSTEMS, INC
Publications: Abstracts Accepted in 2012
• Over 20 Abstracts Accepted and Presented in 2012
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 Orsi F. Role of regional therapies compared with advances in systemic
treatment for melanoma
treatment for melanoma
26 DELCATH SYSTEMS, INC
2013 Abstracts
• Abstracts presented in Q1 2013
• Other accepted abstracts to be presented
o Forster M. Percutaneous hepatic perfusion for unresectable melanoma or sarcoma to the
liver: a single institution experience.
liver: a single institution experience.
o Testori A. Chemosaturation therapy with percutaneous hepatic perfusion for
unresectable liver metastases: the European Institute of Oncology (EIO) experience.
unresectable liver metastases: the European Institute of Oncology (EIO) experience.
o Ferrucci P. Chemosaturation with percutaneous hepatic perfusions (CS-PHP) of melphalan
for hepatic metastases: a comparison between old and new-generation high-efficiency
filters. CIRSE 2013
for hepatic metastases: a comparison between old and new-generation high-efficiency
filters. CIRSE 2013
27 DELCATH SYSTEMS, INC
2013 Planned Publications
• Agarwala, et al. “Treatment of Melanoma Liver Metastases: Impact on
Overall Survival” (Submitted)
Overall Survival” (Submitted)
• Ferrucci, et al. “Experience with Generation 1 Filters vs Generation 2
Filters” Under Review
Filters” Under Review
• Alexander, et al. “Review of Percutaneous Hepatic Perfusion for Ocular
Melanoma Liver Metastases” (Submitted) to be published in American
Oncology and Hematology
Melanoma Liver Metastases” (Submitted) to be published in American
Oncology and Hematology
• Zager, J. “Moffitt Cancer Center Experience with PHP”, accepted to the
Journal of Surgical Oncology, planned early 2014 full publication
Journal of Surgical Oncology, planned early 2014 full publication
• 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 fall 2013 publication
Percutaneous Hepatic Perfusion of Melphalan for Treatment of Metastatic
Liver Cancer”, final stages of review, hopeful fall 2013 publication
• Phase III and Phase II Publications – In preparation
28 DELCATH SYSTEMS, INC
ODAC Summary
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
§ 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
29 DELCATH SYSTEMS, INC
ODAC Summary
§ 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
30 DELCATH SYSTEMS, INC
ODAC Summary
§ Prophylactic growth factor support, which is used to treat neutropenia,
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
§ 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
31 DELCATH SYSTEMS, INC
ODAC Summary
In FDA’s presentation at ODAC, FDA disagreed with this
adjudication and added three additional deaths, for a total of a 7%
percent death rate, in the Phase 2 and Phase 3 programs
adjudication and added three additional 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
§ 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
32 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)