Author: [email protected]

Tumour stromal morphology impacts nanomedicine cytotoxicity in patient-derived xenografts.

It is challenging to evaluate how tumour pathophysiology influences nanomedicine therapeutic effect; however, this is a key question in drug delivery. An advanced analytical method was developed to quantify the spatial distribution of drug-induced effect in tumours with varied stromal morphologies. The analysis utilises standard immunohistochemistry images and quantifies the frequency of positive staining as a function of distance from the stroma. Two stromal morphologies – Estuary and Tumour Island – were classified in 28 tumours from a lung cancer explant model in mice treated with liposomal doxorubicin. Analysis demonstrated that Estuary-like tumours presented a highly convoluted tumour-stroma interface, with most tumour cells in close proximity to vessels; these tumours were 8.8-fold more responsive to liposomal doxorubicin than were Tumour Island-like tumours, which were nearly unresponsive to liposomal doxorubicin. SDARS analysis allows the relative treatment effect to be assessed in tumours individually, and enables investigation of nanomedicine delivery in complex tumour pathophysiologies.
Advances in nanotechnology have brought about many novel treatment modalities for cancer. Nonetheless, there is no standard evaluation technique for tumor cells’ drug response. The authors here utilized patient-derived tumour xenograft (PDTX) models to have a more translatable pre-clinical evaluation platform for nanomedicine drugs. They then used advanced imaging acquisition technique to analyze tumor stromal morphology, which they named Spatial Distribution of Apoptosis Relative to Stroma (SDARS). The findings would have significant clinical impact as it would help predict the eventual clinical drug response.
Copyright © 2015 Elsevier Inc. All rights reserved.

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Cost of biologics per treated patient across immune-mediated inflammatory disease indications in a pharmacy benefit management setting: a retrospective cohort study.

Pharmacy benefits management companies have emerged as the national standard for the management of prescription drugs in the United States. The objective of this study was to estimate the annual costs per treated patient of 8 biologics indicated for select immune-mediated inflammatory diseases: moderate to severe rheumatoid arthritis, moderate to severe plaque psoriasis, active psoriatic arthritis, and/or active ankylosing spondylitis.
Using the Medco pharmacy benefits-management database, data from patients aged 18 to 63 years with ≥1 claim for abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, or ustekinumab, dated between January 1, 2008 and August 31, 2011, were collected. Eligible patients were continuously enrolled for ≥180 days before and 360 days after the date of the first biologic claim (index date), and had ≥1 claim associated with a diagnosis of rheumatoid arthritis, moderate to severe plaque psoriasis, active psoriatic arthritis, and/or active ankylosing spondylitis in the 180 days before or 30 days after the index date. The annual total costs per treated patient were calculated as the total dose of the index biologic and all other biologics for which there was a claim in the postindex period, multiplied by the wholesale acquisition cost as of October 1, 2013, plus the costs associated with administrations (calculated as number of infusions multiplied by the 2013 Medicare Physician Fee Schedule costs).
Within the study population (N = 8306; 5356 (64.5%) women, 2950 men (35.5%), average age: 42.3 years (SD: 10.0)), the most commonly used biologics were etanercept (43.1%), adalimumab (31.0%), and infliximab (17.0%), which accounted for 91.1% of all biologic prescriptions. Total costs per treated patient across indications were as follows: adalimumab, $23,427 to $26,304; infliximab, $22,824 to $28,907; and etanercept, $21,468 to $27,748, whereas abatacept, certolizumab, golimumab, rituximab, and ustekinumab were associated with a larger range: $17,017 to $41,888.
The present study provides insight into the prescribing patterns and cost differences among 8 biologic agents used for the treatment of immune-mediated inflammatory diseases. This information may prove useful when designing a pharmacy benefits-management formulary.
Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

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CytRx to Present New Data Using Its Proprietary LADR™ Technology at the 2016 American Association for Cancer Research Annual Meeting

On March 22, 2016 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that it will present two posters with new preclinical data based on its proprietary LADR technology at the upcoming 2016 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 16-20, 2016, being held at the Ernest N. Morial Convention Center in New Orleans, Louisiana (Press release, CytRx, MAR 22, 2016, View Source [SID:1234509819]).

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Highlights include data on DK049, CytRx’s next albumin-binding drug conjugate nominated for clinical development, which demonstrated superior anti-tumor efficacy compared to gemcitabine in human patient-derived tumor xenograft models of non-small cell lung cancer, ovarian cancer and pancreatic cancer. DK049 decreases the clearance and drug resistance mechanisms that limit the effectiveness of gemcitabine, one of the most commonly used chemotherapy drugs. As a result, DK049’s superior anti-tumor efficacy was achieved using a significantly reduced dose compared to gemcitabine. CytRx plans to commence clinical trials with DK049 in the second half of this year.

CytRx’s second poster details the broad capabilities of the Company’s LADRTM (Linker Activated Drug Release) technology platform. A key advantage is a suite of versatile linkers with the ability to control the release profile of potent cytotoxic agents between 1-50 hours to create personalized therapies for specific cancers. DK049 and the LADRTM technology platform were created in-house at CytRx’s drug discovery lab in Freiburg, Germany.

"The posters that will be presented highlight for the first time the uniquely tunable nature of the LADRTM platform and its ability to create novel drug candidates, like DK049, with superior anti-tumor activity," said Felix Kratz, PhD, CytRx’s Vice President of Drug Discovery.

The following CytRx abstracts have been selected for AACR (Free AACR Whitepaper) poster presentations:

Title: DK049, a novel acid-sensitive prodrug of gemcitabine: design, in vitro properties and in vivo efficacy
Date/Time: Monday, April 18, 1:00pm – 5:00pm CDT
Session Title: Drug Delivery; Poster Section 15, Abstract #2061
Title: LADR: A novel linker activated drug release technology for drug delivery
Date/Time: Wednesday, April 20, 8:00am – 12:00pm CDT
Session Title: Drug Design; Poster Section 21, Abstract #4858

Daiichi Sankyo and ArQule Announce Continuation of METIV-HCC Phase 3 Study of Tivantinib in Second-Line Hepatocellular Carcinoma

On March 22, 2016 ArQule, Inc. (Nasdaq: ARQL) and Daiichi Sankyo reported that the independent data monitoring committee (DMC) of the METIV-HCC study conducted the planned interim assessment and it was determined the trial will continue to its final analysis (Press release, ArQule, MAR 22, 2016, View Source [SID:1234509818]).

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METIV-HCC is a biomarker-selected, double-blind, placebo-controlled, pivotal phase 3 study evaluating tivantinib (2:1) versus best supportive care in previously systemically-treated patients with MET-high, inoperable HCC, with overall survival as the primary endpoint.

The interim analysis was triggered when at least 60 percent of the target number of events occurred. The final analysis will take place when 100 percent of the target number of events occurs. The METIV-HCC trial completed patient accrual in December 2015 with more than 300 patients with MET-high HCC enrolled.

About Hepatocellular Carcinoma (HCC)
Liver cancer is the sixth most common cancer globally with 782,000 new cases in 2012 and is the second most common cause of cancer-related death with 745,000 deaths in 2012.1 HCC accounts for about 90 percent of primary liver cancers.2 Cirrhosis, chronic hepatitis B and C and smoking are recognized worldwide as factors increasing the risk of HCC.2

About MET and Tivantinib (ARQ 197)
Tivantinib is an oral MET inhibitor, currently in phase 2 and phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth factor receptor) antibodies such as cetuximab and panitumumab.

In clinical trials to date, treatment with tivantinib has been generally well tolerated and has shown clinical activity in a number of tumors studied. Tivantinib has not yet been approved for any indication in any country.

In December 2008, ArQule and Daiichi Sankyo signed a licensing, co-development and cocommercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan. 2 In November 2015, ArQule exercised its co-commercialization option for tivantinib in the U.S. A co-commercialization agreement is expected to be finalized in 2016.

JOINT PROMOTION AGREEMENT ON ANTIEMETIC AGENT WITH HELSINN THERAPEUTICS INC. IN THE UNITED STATES REVISED Eisai to Return All Rights to Promote and Distribute AKYNZEO(R) (netupitant/palonosetron) to Helsinn Therapeutics Inc.

On March 22, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that its U.S. subsidiary Eisai Inc. has agreed to revise the joint promotion agreement with Helsinn Healthcare S.A. (Headquarters: Lugano, Switzerland, Group Vice Chairman and CEO: Riccardo Braglia, "Helsinn") for their chemotherapy-induced nausea and vomiting (CINV) franchise (Press release, Eisai, MAR 22, 2016, View Source [SID:1234509811]).

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Under the new arrangement, from April 1, 2016, Helsinn Therapeutics Inc., the U.S. affiliate of Helsinn ("Helsinn U.S."), will obtain exclusive rights to promote and sell AKYNZEO (netupitant/palonsetron), its oral fixed dose combination product for the prevention of CINV. AKYNZEO had previously been co-promoted in the United States by both Helsinn U.S. and Eisai Inc. As part of the revised agreement, Eisai and Helsinn U.S. will continue to co-promote ALOXI (palonosetron HCl) injection in the United States for CINV.

Moving forward, Eisai Inc. will focus on further contributing to patients with ALOXI through this revised joint promotion agreement with Helsinn U.S., along with Eisai’s in-house anticancer agents Halaven and Lenvima.


1. About AKYNZEO
AKYNZEO is a new oral fixed combination that targets two critical signaling pathways associated with CINV, by combining netupitant, an NK1 receptor antagonist, with palonosetron, a 5-HT3 receptor antagonist. Marketing authorization applications for AKYNZEO are currently being submitted in countries throughout the world.