Archive for the ‘Vaccine Studies’ Category

Distant Sarcomas Shrunk By Genetically Reprogrammed HSV

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Posted 13 Jul 2010 — by James Street
Category Vaccine Studies

08 Jul 2010

Scientists have used a genetically reprogrammed herpes virus and an anti-vascular drug to shrink spreading distant sarcomas designed to model metastatic disease in mice – still an elusive goal when treating humans with cancer, according to a study in the July 8 Gene Therapy.

Less than 30 percent of patients with metastatic cancer survive beyond five years, despite the aggressive use of modern combination therapies, including chemotherapy. This creates a significant need for new sarcoma therapies to treat metastatic disease, said Timothy Cripe, M.D., Ph.D., a physician/researcher in the division of Hematology/Oncology at Cincinnati Children’s Hospital Medical Center and the study’s senior investigator.

The study results are even more significant because the oncolytic herpes virus, HSV-rRp450, was given to the mice systemically to attack tumors via the blood stream instead of being injected directly into tumors.

“Systemic bio-distribution has been a major stumbling block for using virus vectors in gene transfer and virotherapy to treat cancer, but we show that viruses can be used systemically by giving them intravenously to get an anti-tumor effect,” Dr. Cripe said.

Also important to results of the current study was using the virus in conjunction with a drug (bevacizumab) that blocks the growth of tumor feeding-blood vessels. In the current study, researchers focused on spreading Ewing sarcoma and Rhabdomyosarcoma – cancers that form in muscle, bone and connective tissue.

Anti-angiogenic agents like bevacizumab are usually given first in combination cancer therapies because they help enlarge intercellular openings to tumor cells and ease the delivery of drugs, such as chemotherapies. In this study, however, the researchers discovered that bevacizumab has to be given after the virus to maximize the anti-tumor effect of the combined therapy. In fact, giving bevacizumab first lowered the virus’s uptake in cancer cells.

The rRp450 oncolytic virus used in the study was derived from herpes simplex type 1. The virus was genetically modified by scientists by removing a gene that makes the virus unable to replicate efficiently in dormant cells. This causes the virus to selectively target and replicate in rapidly growing cancer cells while leaving normally dormant healthy tissue cells alone.

After removing the one gene from the virus, researchers replaced it with a gene that encodes an enzyme that activates a class of anti-tumor chemotherapies called oxazaphosphorines. The overall therapeutic approach is for the virus to infect and degrade the cancer cells and then activate chemotherapy agents as anti-angiogenic agents cut off vascular growth and blood supply to the tumors.

In the current study, however, researchers treated the mice only with rRp450 and the anti-angiogenic drug bevacizumab. This allowed them to test whether the virus could be given systemically, how anti-angiogenic drugs affected virus tumor uptake and the impact this had on tumor growth.

In mice receiving bevacizumab prior to the rRp450, overall tumor shrinkage averaged 40 percent. In mice receiving rRp450 before bevacizumab, tumor size was reduced by an average of 75 percent. The researchers also reported that mice treated with rRp450 before bevacizumab had longer survival rates.

Results of the current study could be used immediately to help design subsequent research into treatment protocols for oncolytic viruses, particularly clinical trials involving combination therapeutic strategies, Dr. Cripe said. Clinical trials are underway in the United States and Europe using oncolytic herpes viruses similar to the one used in the current study.

Other researchers involved in the current study include the first author, Francis Eshun, M.D., and Mark Currier, Rebecca Gillespie, Jillian Fitzpatrick and William Baird, all of the Division of Hematology/Oncology at Cincinnati Children’s and its Cancer and Blood Diseases Institute. Funding support for the study from the Cincinnati Children’s Division of Hematology/Oncology, teeoffagainstcancer.org, the Katie Linz Foundation, the Limb Preservation Foundation, the American Cancer Society and the National Institutes of Health.

Source:
Nick Miller
Cincinnati Children’s Hospital Medical Center

Article URL: http://www.medicalnewstoday.com/articles/194121.php

Main News Category: Cancer / Oncology

Also Appears In:  Genetics,  Infectious Diseases / Bacteria / Viruses,  Vascular,

Onyvax Reports Early Success with Osteosarcoma Cancer Vaccine

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Posted 26 Feb 2010 — by James Street
Category Vaccine Studies

Onyvax Reports Early Success with Osteosarcoma Cancer Vaccine

LONDON APR 19, 2005 (Agence de Presse Medicale for Reuters Health) – The private UK biotech company Onyvax on Tuesday reported positive phase l/ll clinical trial results for its cancer immunotherapy ” Onyvax-105″ in children and young adults with osteosarcoma.

The vaccine targets the CD55 antibody that is overexpressed in many types of cancer as part of its defence against immune system attack. The investigational drug was given to 31 pediatric and young adults with high-grade osteosarcoma who had completed best standard therapy.

The results showed that most patients receiving intensive chemotherapy for osteosarcoma could still mount an immune response to the cancer vaccine approach, the company said in a statement.

Although the trial was designed to assess feasibility of immunotherapy rather than efficacy, two patients remained tumour-free more than 4 years later.

Dr. Pritchard-Jones, Professor of Childhood Cancer at the Royal Marsden Hospital, London, and principal investigator of the study, said: “This group of patients has limited treatment options and a very poor prognosis.

“We were pleased to see a high percentage of patients developing immune responses to Onyvax-105, confirming that an immunomodulatory approach is feasible in combination with the intensive chemotherapy that these children and young adults require.

“Moreover, it is very unexpected for any patients at this stage of the disease to remain free of recurrent disease for long.”

The company reported last year that its lead cancer vaccine, Onyvax-P, had doubled progression free survival time in a small nonrandomised study of men with advanced prostate cancer. Further results are expected this year.

Onyvax-105 Shows Promising Results in Osteosarcoma

Researchers affiliated with the UK Children’s Cancer Study Group have reported that a vaccine known as Onyvax-105 (105AD7 ) elicits an immune response in patients with osteosarcoma. The details of this report appeared in the British Medical Journal.[1]

Osteosarcoma is a disease of younger individuals that is treated with surgery, radiation and chemotherapy. However, despite optimal therapy, the majority of patients with advanced disease ultimately relapse. Onyvax-105 is an anti-idiotypic monoclonal antibody that mimics the tumor associated antigen 791/gp72, which was developed by Onyvax Limited.[2] A previous randomized study in patients with advanced colorectal cancer comparing Onyvax-105 to placebo failed to show efficacy, a result attributed to a high tumor burden.[3]

In the UK study, vaccine was administered to 31 pediatric and young adult patients with osteosarcoma after completion of chemotherapy. Significant T-cell responses were observed in 71% of patients. Over 50% of patients showed antigen-specific gamma interferon secretion, and 31% showed an antibody response. The vaccine was described as well tolerated. They also reported that two patients with possible clinical responses continued immunization for two years and are disease-free for over 5 years. The authors propose to carry out a randomized trial to determine if this vaccine is effective.

Comments: It is difficult to know from this trial if Onyvax-105 will be effective in Osteosarcoma or other diseases. This vaccine will need to be tested in randomized trials in patients with minimal residual disease and a high probability of relapse.

References:

[1] Pritchard-Jones, K, Spendlove K, Wilton C, et al. Immune responses to the 105AD7 human anti-idiotypic vaccine after intensive therapy for osteosarcoma. British Medical Journal advance online publication. March 2005;doi:101038/sj.bjc.6602500.
[2] Press release for April 19, onyxax.com
[3] Maxwell-Armstrong, CA, Durrant LG, Buckley TJD, et al. Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer. British Medical Journal. 2001;84:1443-1446.

More about Mepact-Junovan 3

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Posted 25 Feb 2010 — by James Street
Category General Cancer Research, Vaccine Studies

IDM Pharma Announces Updated Data From Mifamurtide (L-MTP-PE) Compassionate Access Program

- Data Presented at the 21st Annual Meeting of The American Society of
Pediatric Hematology/Oncology (ASPHO) Meeting -

IRVINE, Calif., May 15 /PRNewswire-FirstCall/ — IDM Pharma, Inc. (the
Company) (Nasdaq: IDMI) today announced the presentation of updated data
from a compassionate access program evaluating mifamurtide (L-MTP-PE) in
patients with lung metastases as a result of the progression of
osteosarcoma, a rare and often fatal bone tumor that typically affects
children and young adults. The data show that L-MTP-PE in combination with
other therapies is safe, well- tolerated and exhibited signs of disease
control.

The compassionate access program provides L-MTP-PE treatment to
patients who have either failed or cannot tolerate treatment with existing
therapies compared to the Phase 3 pivotal study, which evaluated newly
diagnosed patients.

“The results that we have seen to date from the Phase 3 clinical trial
in patients with non-metastatic osteosarcoma are being supported in
patients with lung metastases as the L-MTP-PE compassionate access
experience continues to be encouraging,” said Peter Anderson, M.D., Ph.D.,
principal investigator and professor of pediatrics, Children’s Cancer
Hospital at The University of Texas M. D. Anderson Cancer Center in
Houston. “With a formalized protocol now in place, we can address the
increasing number of requests for compassionate access to L-MTP-PE and meet
the unmet needs of certain patients by providing this much needed treatment
option.”

Study design and findings

Twenty-nine high-risk osteosarcoma patients (ages 10 – 21) were
enrolled and 27 have been treated with L-MTP-PE in the compassionate access
program to date (May 8, 2008). Patients in the program had documented
diagnosis of high grade osteosarcoma with relapsed or recurrent disease
(locally or metastatic) with resectable or not completely resectable
disease, or who are unable to complete recommended chemotherapy due to
toxicity.

L-MTP-PE (2 mg/m2 IV over 1 hour) was administered twice a week for 12
weeks followed by once a week for 24 weeks. In addition, some patients in
the program were also treated with other agents including aerosol
recombinant granulocyte monocyte colony stimulating factor (GM-CSF) an
immune stimulating agent (n=20), ifosfamide (n=4), and/or gemcitabine
(n=2).

Results to date are as follows:
– Nine patients are alive with disease.
– Nine patients have no evidence of disease.
– Nine patients have died.
– There are two patients for whom the status is unknown.
Treatment with L-MTP-PE combined with other agents including aerosol
GM- CSF was generally well tolerated. Patients treated with chemotherapy
had no unexpected toxicities and toxicity from L-MTP-PE infusions was
minimal. There were no reports of grade 3 or 4 drug-related toxicities with
the exception of fever grade 3 and flu-like symptoms with the first dose.
This was prevented with ibuprofen and acetaminophen after subsequent doses.
One patient developed pleural and pericardial effusion that was possibly
L-MTP-PE and/or GM-CSF related and the patient was removed from the study.

In March, the Company announced that it had formalized a clinical
protocol with the FDA, which provides L-MTP-PE to eligible, high-risk
osteosarcoma patients through a compassionate access study. The
compassionate access study is being conducted initially at M. D. Anderson
and Memorial-Sloan Kettering Cancer Center in New York.

“Patients are our first priority and we are committed to providing
L-MTP- PE to those who desperately need treatment,” said Timothy P.
Walbert, president and chief executive officer, IDM Pharma. “The potential
survival and quality of life benefits for patients treated with L-MTP-PE
continue to be supported through physician experience and we remain
committed to advancing L- MTP-PE through the European and U.S. regulatory
processes to bring this important treatment to market.”

Update on L-MTP-PE Regulatory Status

In January 2008 the Company announced that following presentation of
data at an oral explanation hearing before the Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency, the CHMP
determined in a non-binding opinion that L-MTP-PE suggested a possible
clinical benefit in terms of survival and granted the Company a clock stop,
or time extension. The clock stop allows the Company additional time to
respond to all the remaining questions regarding the marketing
authorization application for L-MTP-PE (MAA). The CHMP has requested
clarification of the existing data in order to gain assurance about the
quality of the data before drawing any final conclusions from the data
presented. In addition, the Company is required to address a number of
remaining questions relating to chemistry, manufacturing and controls (CMC)
and the Company expects to provide responses and data regarding these
issues to the CHMP in advance of its meeting scheduled for June 23-26,
although the CHMP may have additional questions or require additional
information regarding these issues. In April, the European regulatory
authorities conducted an inspection of the Children’s Oncology Group (COG)
to assess the quality of the overall survival data from the 2006
confirmatory database included in our applications for regulatory approval,
and to review Good Clinical Practices compliance of COG in terms of patient
randomization and stratification, overall survival data collection, and
study monitoring. The Company supported the COG in this effort.

The Company expects to receive a final opinion from the CHMP in the
third quarter and a final decision from the European Commission in the
fourth quarter of 2008.

As previously announced, in the United States the Company continues to
work with the COG as well as external experts and advisors to gather
patient follow up data from the Phase 3 clinical trial of L-MTP-PE and to
respond to other questions in the non-approvable letter the Company
received from the U.S. Food and Drug Administration (FDA). The Company
expects to submit the amended New Drug Application (NDA) in the fourth
quarter of 2008.

L-MTP-PE was granted orphan drug status in the United States in 2001
and in Europe in 2004. In Europe, the MAA was filed in November 2006 and in
the U.S, the NDA was submitted to FDA in October 2006 and was accepted for
review in December 2006.

About Osteosarcoma

Between two and three percent of all childhood cancers are
osteosarcoma. Because osteosarcoma usually develops from osteoblasts, it
most commonly affects children and young adults experiencing their
adolescent growth spurt. Boys and girls have a similar incidence rate until
later in their adolescence, when boys are more commonly affected. While
most tumors occur in larger bones, such as the femur, tibia, and humerus,
and in the area of the bone that has the fastest growth rate, they can
occur in any bone. The most common symptom is pain, but swelling and
limited movement can occur as the tumor grows.

Osteosarcoma is an orphan disease with fewer than 1,000 new cases
diagnosed in the United States each year. A similar incidence of the
disease exists in Europe. According to the Children’s Oncology Group, the
survival of children with osteosarcoma has remained at 60-65 percent since
the mid-1980s. The standard treatment for osteosarcoma is tumor resection
with combination chemotherapy before and after surgery.

About IDM Pharma

IDM Pharma is focused on the development of innovative cancer products
that either destroy cancer cells by activating the immune system or prevent
tumor recurrence by triggering a specific adaptive immune response. IDM
Pharma is dedicated to maximizing the full therapeutic and commercial
potential of each of its innovative products to address the needs of
patients and the physicians who treat these patients.

For more information about the company and its products, visit

http://www.idm-pharma.com.

Forward-Looking Statements

This press release includes forward-looking statements that reflect
management’s current views of future events including the objectives of the
compassionate access study, the Company’s plans to address the remaining
questions with respect to the MAA for L-MTP-PE during the clock-stop
granted by the CHMP, and the expected timing of a final opinion from the
CHMP and of a final regulatory decision regarding the MAA in the European
Union, as well as the Company’s plans to collect, analyze and submit
additional Phase 3 data in an amended NDA for L-MTP-PE, including the
expected timing for such amended NDA, and to respond to other matters
raised by the FDA. Actual results may differ materially from the
forward-looking statements due to a number of important factors, including,
but not limited to, whether the Company will be able to respond to the
remaining issues with regard to the MAA, including verification of data
quality and CMC items, to the satisfaction of the CHMP, whether the CHMP
will ask the Company for further information at or following the June 2008
meeting to address remaining issues with regard to the MAA, which would
delay the timing of a final opinion from the CHMP, whether the final
opinion of the CHMP will be consistent with the non-binding opinion of the
CHMP, whether the European Commission will follow the final opinion of the
CHMP once issued, whether the timing for the final opinion of the CHMP and
the regulatory decision in Europe will occur as expected by the Company,
the possibility that additional data from the Phase 3 clinical trial of
L-MTP-PE and other information in any amendment to the NDA for L-MTP-PE
submitted by the Company may not provide adequate support for regulatory
approval of L-MTP- PE in the United States within the timeframe expected by
the Company, if at all, and whether the Company will be able to manufacture
and commercialize L- MTP-PE even if it is approved by regulatory
authorities, and whether the cash resources of the Company will be
sufficient to fund operations as planned. These and other risks affecting
the Company and its drug development programs, intellectual property
rights, personnel and business are more fully discussed in the Company’s
Quarterly Report on Form 10-Q filed with the SEC for the quarter ended
March 31, 2008 and other periodic reports filed with the SEC. The Company
expressly disclaims any intent or obligation to update these
forward-looking statements, except as required by law.

SOURCE IDM Pharma, Inc.

Mepact (renamed Junovan) finally produced in San Diego

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Posted 25 Feb 2010 — by James Street
Category Human osteosarcoma research, Vaccine Studies

IDM Successfully Manufactures First Lot of Junovan(TM) to Support Filing for Marketing Authorization

SAN DIEGO, Sept. 22 /PRNewswire-FirstCall/ — IDM Pharma, Inc.
(Nasdaq: IDMI) today announced that it has produced a first lot of Junovan
(previously known as L-MTP-PE or MEPACT) that meets current specifications as
well as the prior specifications for the product used in the conduct of the
Phase III study in patients with high grade non-metastatic osteosarcoma, the
indication for which IDM will be seeking marketing authorization. The Company
achieved this important milestone with its key contract manufacturers, Genzyme
Pharmaceuticals, Liestal, Switzerland; NOF Corporation, Tokyo, Japan; Ben
Venue Laboratories, Cleveland, Ohio and Solvias AG, Basel, Switzerland.
“We are pleased to be working with world-class contract manufacturers as
this is an essential step for IDM to ensure we have GMP product that not only
meets current requirements, but that will also be sufficiently comparable to
the previous product utilized during clinical development so that the
development data can be used to support approval,” said Jean-Loup
Romet-Lemonne, IDM’s Chairman and CEO. “We intend to initiate comparability
studies with the new IDM product immediately. A proposed protocol for
demonstration of comparability is currently under review by the FDA.”

About Junovan(TM)
Junovan is a liposomal formulation of MTP-PE (Muramyl Tripeptide
Phosphatidylethanolamine) specifically designed for in vivo targeting of
macrophages by intravenous infusion. It is a fully synthetic derivative of
muramyl dipeptide, a naturally occurring component of bacterial cell walls.
Junovan has been evaluated in Phase II and Phase III clinical trials for the
treatment of osteosarcoma. The IDM Phase III trial was the largest ever
published in osteosarcoma and demonstrated improvement in disease-free and
overall survival among patients with non-metastatic, resectable osteosarcoma,
who were treated with L-MTP-PE, corresponding to a relative reduction in the
risk of recurrence of 25% and a relative reduction in the risk of death of
30%. Adverse events associated with the use of Junovan are generally mild to
moderate and thought to be associated with its biological activity. Severe
adverse events in the Phase III study were those typically associated with
high dose multiple-drug chemotherapy, which was used together with Junovan in
the Phase III trial.
Junovan for the treatment of osteosarcoma is IDM’s lead product candidate.
Junovan has received Orphan Drug Status in both the U.S. and EU, and the
Company is working with U.S. and EU regulatory agencies regarding the
appropriate pathway for product marketing approval. The Company expects to
receive regulatory approval for Junovan in the U.S. and EU in 2007.

About IDM Pharma
IDM is a biopharmaceutical company focused on the development of
innovative products that activate the immune system to treat cancer and
infectious disease. IDM is currently developing three types of products: the
first is designed to destroy cancer cells by activating innate immunity, the
second to prevent tumor recurrence by triggering a specific adaptive immune
response, and the third to treat chronic infectious disease with therapeutic
vaccines.
IDM currently has 7 products in clinical development. The most advanced
product, Junovan(TM), has completed a Phase III clinical trial in
osteosarcoma. Three products are in Phase II clinical trials in bladder
cancer, melanoma and non-small cell lung cancer, and three are in Phase I in
colorectal cancer, hepatitis B and HIV infection.
IDM has major product development partnerships with SANOFI-AVENTIS in
cancer immunotherapy, and with INNOGENETICS in vaccine development for the
treatment of chronic hepatitis B and C and papilloma virus infection. MEDAREX
and SANOFI-AVENTIS are corporate partners and shareholders of IDM or its
affiliate since 1993 and 2001 respectively.

For more information, visit http://www.idm-pharma.com.

SOURCE IDM Pharma, Inc.
Issuers of news releases and not PR Newswire are solely responsible for the accuracy of the content.
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Mepact (Junovan) provides a significant increase in Osteosarcoma disease free survival

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Posted 25 Feb 2010 — by James Street
Category Human osteosarcoma research, Vaccine Studies

Mepact, IDM’s Most Advanced Product, Receives ”Orphan Medicinal Product” Designation for the Treatment of Osteosarcoma in the European Union

PARIS, July 8, 2004 – IDM (Immuno-Designed Molecules), a biopharmaceutical company specialized in the development of immunotherapy products for the treatment and control of cancer, announces today that the European Commission has granted its product, Mepact, “orphan medicinal product” designation for the treatment of osteosarcoma. Designation was granted following the positive opinion given by the European Medicines Agency (EMEA) and its Committee for Orphan Medicinal Products (COMP). Mepact obtained “orphan drug” status in the United States in June 2001.

Mepact (L-MTP-PE) is an immune system stimulant designed to promote the destruction of cancer cells by activating macrophages present in the body. A randomized Phase III trial on Mepact administered after surgical resection of tumor, in association with chemotherapies was carried out on close to 800 patients who had recently been diagnosed with Osteosarcoma. The statistical analysis of data from the trial indicates that Mepact provides a significant increase in the disease free survival, as well as a significant increase in the overall survival of patients whose treatment includes Mepact versus treatment with chemotherapy alone. The most frequent adverse events were those typically associated with intensive chemotherapy.

Osteosarcoma is the most common form of bone cancer. It primarily occurs in children and adolescents. The incidence is approximately one thousand new cases per year both in the United States and in Europe.

The European Commission grants “orphan medicinal product” designation to medicines products targeting diseases whose prevalence in the European Union does not exceed 5 per 10,000 persons. To encourage the development of new drugs to treat rare diseases, “orphan medicinal product” designation gives companies specific financial and regulatory incentives as well as market exclusivity that, in the European Union, last for ten years after obtaining marketing authorization.

IDM is currently completing its application to regulatory authorities in order to gain approval to market Mepact in the European Union and the United States.

IDM — The Immunogenics Company(R)

IDM is a biopharmaceutical company focused on the development of innovative products to treat and control cancer while maintaining the patient’s quality of life. IDM is currently developing two lines of products: one aiming at the destruction of residual cancer cells after the use of traditional therapies, and the other to prevent tumor recurrence by triggering an immune response. IDM’s most advanced product has completed a Phase III clinical trial, five other products are in clinical trials and five are in preclinical development.

For more information, please visit IDM’s Web site, http://www.idm-biotech.com.

CONTACT: IDM Nadine Sciacca, +33 (0) 1 40 09 04 11 nsciacca@idm-biotech.com idm@idm-biotech.com