10 oktober 2012: Bron: Int. Journal of Oncology

Toegevoegd aan onderstaande informatie de resultaten uit een fase II studie bij levertumoren met het virus onder codenaam NV2010 (G-207). Deze studie geeft aan dat dit virus de groei van levertumoren kan stoppen en zelfs levertumoren weer kwetsbaar kan maken voor lokale chemospoelingen. Hier het abstract van gerandomiseerde fase II studie:

Phase II efficacy results using an oncolytic herpes simplex virus (NV1020) in patients with colorectal cancer metastatic to liver (mCRC)

S. K. Geevarghese, A. Chen, D. A. Geller, H. A. de Haan, A. Iagaru, A. Knoll, J. Nemunaitis, T. R. Reid, D. Y. Sze and K. Tanabe

Vanderbilt University, Nashville, TN; MediGene Inc, San Diego, CA; University of Pittsburgh, Pittsburgh, PA; Stanford University School of Medicine, Stanford, CA; Mary Crowley Medical Research Center, Dallas, TX; University of California, San Diego, San Diego, CA; Stanford University, Stanford, CA; Massachusetts General Hospital, Boston, MA

4089

Background: NV1020 is a genetically engineered oncolytic Herpes virus. Published Phase 1 dose-ranging results reported no significant related toxicity except for a mild (<24 hr) viral syndrome. Initial Phase 2 tumor response data using the optimal biological dose (OBD) are now presented. Methods: Patients with heavily pretreated, progressing liver mCRC received 4 doses of NV1020 (1 X10⁸ pfu) by weekly hepatic artery infusion followed by two cycles of conventional chemotherapy. Follow-up (1 year) evaluation included 4 X 3-monthly scans, then telephone contact to determine survival. Blinded, independent radiologists interpreted CT (modified RECIST) and FDG PET (EORTC) scans. Results: All 22 patients had prior 5FU-based treatment: 77% and 58% also had oxaliplatin or irinotecan, respectively (50% both agents); 86% had one targeted therapy (24% 2 such agents); 29% had radiofrequency ablation. Mean time from primary resection was 95 weeks, mean CEA was 182 ng/mL, and 55% had pulmonary lesions. Two patients received only 2 NV1020 infusions due to rapidly progressing disease. Virus tolerability was unchanged from Phase 1 and no related, serious or Grade 4 toxicity was found. NV1020 neutralizing antibodies rose in all patients but no NV1020 was shed (saliva, skin). After NV1020 alone, 10/22 (45%) and 8/20 (40%) on CT and PET, respectively, showed stable disease. 21 patients subsequently received chemotherapy, 45% with drugs to which they were previously refractory and 36% with only one new drug. 14% refused both planned cycles. Best response observed with CT was 55% (1 CR, 1 PR, 10 SD) and 59% (5 PR, 8 SD) with PET. Despite intrahepatic delivery, some remote responses were observed. Response did not correlate with initial tumor size, SUV, or CEA, with time since primary resection, pre- or post NV1020 chemotherapy type. Nine (41%) remain alive > 1 year. Kaplan-Meier median time to progression is 28 weeks (95% CI [9–37]); median survival probability is 52 weeks (95% CI [36–90]). Conclusions: NV1020 stabilizes liver metastases in highly advanced mCRC and may sensitize tumors to salvage chemotherapy resulting in extended overall survival. A controlled Phase 2/3 trial is justified.

3 september 2004: Bron -- Persbericht van Medigene

Na alle mooie nieuws over bv. het Newcastle virus en inbreng van virus door engelse onderzoekers, zie elders onder deze artikelen onder actueel regulier onderzoek, een mooi nieuw initiatief met inbrengen van een kankerdodend virus. Deze week maakte het Amerikaans-Duitse farmaceutisch bedrijf Medigene bekend dat zij een fase I - II trial starten om het effect te testen van het inbrengen van een kankerdodend virus, een herpes simplex virus, in niet operabele tumoren in de lever van darmkankerpatiënten met het adenocarcinoom. Het kankerdodende virus wordt onder de codenaam NV1020 getest. Allereerst op effect, tolerantie en veiligheid. Er wordt zowel getest met het virus alleen als wel in combinatie met chemo bij ca. 30 patienten in 7 verschillende ziekenhuizen in de USA. De patiënten krijgen vier keer het virus teogeeind en daarna nog een chemokuur erachteraan. De uitslagen van deze trial worden medio 2006 verwacht.

MediGene Initiates Clinical Phase I/II Trial of Cancer-Killing Virus NV1020 for the Treatment of Liver Metastases.

MARTINSRIED, Germany and SAN DIEGO, Sept. 2 /PRNewswire-FirstCall/ --
Today the German-American biotech company MediGene AG (Frankfurt, Prime Standard: MDG) announced the initiation of a clinical phase I/II trial of the drug candidate NV1020 for the treatment of liver metastases developing from colorectal cancer. NV1020 is currently developed as a cancer-killing (oncolytic) virus. It is a herpes simplex virus, genetically modified for the specific destruction of tumor cells without harming healthy tissue. The trial will evaluate safety, tolerability and efficacy of NV1020 as well as its synergies with chemotherapy. In this trial, about 30 patients will be treated in up to 7 clinical centres in the USA. The positive results obtained in a clinical phase I trial of NV1020 form the basis for this trial. MediGene expects the results of the phase I/II study by mid 2006. The sales potential for NV1020 is estimated at over 200 million Euros, provided that the three- step clinical development is successful and marketing authorization is granted.
Dr. Peter Heinrich, Chief Executive Officer of MediGene AG, comments: "Cancer-killing viruses like NV1020 are among the most innovative products of today's drug development. If the development of NV1020 proceeds as successfully in the future as it has up to now, MediGene may become the first company wordwide to develop a virus mutant cancer drug to market maturity. This could be a very valuable contribution to improvement in cancer therapy."

NV1020: MediGene's oncolytic herpes simplex virus (HSV) NV1020 is designed to selectively multiply in tumor cells, thus destroying the tumor (oncolysis). The technology is based on the assumption that oncolytic HSV act more selectively and efficiently than conventional cancer therapies, without leading to severe adverse events. They could provide a therapeutic alternative against tumors that are inoperable or have developed a resistance to chemotherapy or radiotherapy. There may be also a synergistic effect of combining oncolytic HSV and standard therapies such as chemotherapy.

Study design: The trial will be composed of a part to determine the appropriate dosage, followed by a phase 2 part investigating tolerability and efficacy utilizing the optimal dose of NV1020. The patients participating in the trial suffer from colorectal adenocarcinoma which cannot be removed by surgery. In the course of the trial, NV1020 is administered to these patients four times, followed by standard chemotherapy. The first study center has been initiated and the first patient has been evaluated for study eligibility.

This press release contains forward-looking statements that involve risks and uncertainties. The forward-looking statements contained herein represent the judgement of MediGene as of the date of this release. These forward- looking statements are no guarantees for future performance, and the forward- looking events discussed in this press release may not occur. MediGene disclaims any intent or obligation to update any of these forward-looking statements.

MediGene(TM) is a trademark of MediGene AG. About MediGene: MediGene AG is a publicly quoted (Frankfurt: Prime Standard), German- American biotechnology company located in Martinsried, Germany and San Diego, USA. MediGene is the first German biotech company with a drug on the market. The company has the most mature drug development pipeline in the German biotech industry (drug candidates undergoing clinical phase I - III trials). In addition, MediGene possesses innovative platform technologies with its HSV technology and the newly acquired EndoTAG(TM) technology. MediGene's core competence lies in research and development of novel approaches for the treatment of various tumor diseases. Thus MediGene focuses on indications of high medical need and economic opportunities.

SOURCE MediGene AG /CONTACT: Julia Hofmann, Public Relations, +49-89-85-65-3324, or Dr. Michael Nettersheim, Investor Relations, +49-89-85-65-2946, both of MediGene AG, fax, +49-89-85-65-2920, or investor@medigene.com

herpes simplex, NV1020, leverkanker, virus, immuuntherapie, RFA, TACE, complementair

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