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Quarta-feira, 19.08.15

Unituxin (dinutuximab) granted EC Marketing Authorisation for treatment of childhood neuroblastoma

Unituxin (dinutuximab) granted EC Marketing Authorisation for treatment of childhood neuroblastoma

Published on August 17, 2015 at 7:21 AM ·

United Therapeutics Corporation (NASDAQ: UTHR) announced today that the European Commission (EC) has granted Marketing Authorisation for Unituxin™ (dinutuximab) for the treatment of high-risk neuroblastoma in patients aged 12 months to 17 years, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and autologous stem cell transplantation (ASCT). Unituxin is administered in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and isotretinoin.

Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence in the European Union of approximately 1500 patients, of whom 50% are diagnosed as having high-risk disease.

The European approval was based on demonstration of improved event-free survival (EFS) and overall survival (OS) in a multicenter, open-label, randomized trial (ANBL0032) sponsored by the US National Cancer Institute under a Cooperative Research and Development Agreement with United Therapeutics and conducted by the Children's Oncology Group (COG).

Trial design and results

The trial randomized (1:1) 226 patients to either the Unituxin/13-cis-retinoic acid (RA) arm or the RA alone arm. Patients in each arm received six cycles of treatment. The Unituxin/RA arm consisted of Unituxin in combination with granulocyte macrophage-colony stimulating factor and RA (cycles 1, 3, and 5), Unituxin in combination with interleukin-2 and RA (cycles 2 and 4), and RA (cycle 6). Patients were 11 months to 15 years of age (median age 3.8 years).

The major efficacy outcome measure was investigator-assessed EFS, defined as the time from randomization to the first occurrence of relapse, progressive disease, secondary malignancy or death. The primary intent-to-treat analysis found an improvement in EFS associated with dinutuximab immunotherapy plus isotretinoin as compared to isotretinoin alone. The two-year estimates of EFS were 66% among subjects receiving dinutuximab immunotherapy plus isotretinoin as compared with 48% in subjects receiving isotretinoin alone (log-rank test p = 0.033) although this difference did not reach formal statistical significance according to the pre-specified plan for interim analyses. In addition, OS was evaluated with 3 years of follow-up after the EFS analysis as a secondary endpoint with a significant improvement observed among ITT subjects randomly allocated to receive dinutuximab immunotherapy plus isotretinoin as compared with isotretinoin alone. The three-year estimates of OS were 80% compared with 67% among subjects receiving dinutuximab immunotherapy plus isotretinoin and isotretinoin alone, respectively (log-rank test p = 0.0165). Long-term overall survival was evaluated with five years of follow up after the EFS analysis and continued to demonstrate a survival advantage for patients who received dinutuximab immunotherapy compared to those who received isotretinoin alone. The five-year estimates of OS were 74% for dinutuximab immunotherapy compared to 57% for isotretinoin alone (log-rank test p = 0.030).

Frequently occurring adverse reactions

The most frequently occurring (more than 30% of patients) adverse reactions reported during the neuroblastoma studies were hypotension (67%), pain (66%), hypersensitivity (56%), pyrexia (53%), urticaria (49%), capillary leak syndrome (45%), anaemia (45%), hypokalaemia (41%), platelet count decreased (40%), hyponatraemia (37%), alanine aminotransferase increased (35%), decreased lymphocyte count (34%) and decreased neutrophil count (31%). Additional adverse reactions characteristic of an allergic response were also reported – including anaphylactic reaction (18%) and bronchospasm (4%).

Posology and method of administration

Unituxin is to be administered by intravenous infusion over five courses at a daily dose of 17.5 mg/m2. It is administered on days 4-7 during courses 1, 3 and 5 (each course lasting approximately 24 days) and on days 8-11 during courses 2 and 4 (each course lasting approximately 28 days).

The treatment regimen consists of Unituxin, GM-CSF, IL-2, and isotretinoin, administered over six consecutive courses.

Source:

United Therapeutics Corporation

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por cyto às 12:08

Quarta-feira, 19.08.15

ImmunoCellular signs agreement with FDA for phase 3 registrational trial of cancer immunotherapy ICT-107

GLIOBASTOMA GBM

ImmunoCellular signs agreement with FDA for phase 3 registrational trial of cancer immunotherapy ICT-107

Published on August 13, 2015 at 8:32 AM ·

ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT: IMUC) announced today that it has reached agreement with the US Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for the phase 3 registrational trial of its cancer immunotherapy ICT-107 to treat patients with newly diagnosed glioblastoma.

The phase 3 trial is designed as a randomized, double-blind, placebo-controlled study of about 400 HLA-A2 positive subjects, which will be conducted at about 120 sites in the US, Canada and the EU. The primary endpoint in the trial is overall survival, which the FDA and EU regulators have stated is the appropriate endpoint for registrational clinical studies in glioblastoma. Secondary endpoints include progression-free survival and safety, as well as overall survival in the two pre-specified MGMT subgroups. Patient enrollment is anticipated to begin in the late third quarter or early fourth quarter of 2015.

A Special Protocol Assessment is a written agreement between the sponsor company and the FDA on the design, clinical endpoints, size and statistical design of a clinical trial intended to form the primary basis of an efficacy claim in the marketing application, such as a biologic licensing application (BLA) or a new drug application (NDA). Final marketing approval depends upon the safety and efficacy results demonstrated in the phase 3 clinical program.

Andrew Gengos, ImmunoCellular's Chief Executive Officer Commented: "We are pleased to have achieved this important milestone, and think that successful completion of the SPA process adds meaningful validation to the ICT-107 phase 3 program and design, especially the use of the gold standard primary endpoint of overall survival. With this SPA in place, we think that ICT-107 is uniquely positioned in the field of immuno-oncology approaches being tested in glioblastoma. We are making significant progress toward establishing our clinical site network and obtaining the necessary institutional review board approvals. We are confident that we are on track to begin patient enrollment in the late third quarter or early fourth quarter of this year."

Source:

ImmunoCellular Therapeutics, Ltd.

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por cyto às 11:37

Quinta-feira, 23.07.15

Dartmouth researchers perform first total syntheses of compounds involved in rapid cell death in leukemia

 

Dartmouth researchers perform first total syntheses of compounds involved in rapid cell death in leukemia

Published on July 22, 2015 at 5:18 AM 

Dartmouth researchers and their colleagues have carried out the first total syntheses of certain compounds involved in excessive cell death in leukemia.

The findings appear in the journal Angewandte Chemie International Edition. A PDF is available on request.

"We anticipate that these compounds will serve as useful tools for dissecting an important but as yet undefined step in the regulation of apoptosis," says senior author Jimmy Wu, an associate professor of chemistry at Dartmouth. "Studies to clarify the biological mechanism by which they operate are ongoing."

The researchers completed the total syntheses of several members of the family of dimeric nuphar alkaloids, which are compounds previously isolated from the yellow pond lily. These are structurally complex molecules that are capable of including apoptosis, or programmed cell death, in certain human leukemia cell lines faster than any other small molecule. The researchers also were able to synthesize some related structures that they predict might exist in nature but have not yet been found.

There have been only two reports that attempt to explain the biological mechanism of action of these molecules. But these are incomplete and more research is required to fully reveal how these compounds work. The Dartmouth-led team's synthetic efforts now provide a means to a steady supply of the active compounds for further study. Preliminary biological tests conducted by co-author Alan Eastman, a professor of pharmacology and toxicology at Dartmouth's Geisel School of Medicine, indicate that all the compounds, both naturally occurring and ones predicted to be exist in nature, are capable of inducing extremely rapid apoptosis in leukemia cells. The researchers are in the process of studying their biological mechanism of action.

"Insufficient apoptosis is strongly linked to cancer and autoimmune disorders," Wu says. "There are also numerous diseases associated with excessive cell death, such as AIDS, Alzheimer's, Huntington's, Parkingson's and ALS. A better understanding of the biological basis of how the dimeric nuphar alkaloids can so rapidly induce cell death may lead to novel points of intervention for the design of prospective therapeutics and other diseases attributed to abnormal apoptosis."

Source:

Dartmouth College

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por cyto às 22:57

Terça-feira, 21.07.15

Novel cancer drug candidate developed in Singapore advances into clinical trials

 

Novel cancer drug candidate developed in Singapore advances into clinical trials

Published on July 17, 2015 at 2:01 AM

A made-in-Singapore cancer drug has advanced into clinical trials, charting a milestone in Singapore's biomedical sciences initiative that will go towards improving the lives of cancer patients in Singapore, and worldwide. The Agency for Science, Technology and Research (A*STAR) and Duke-National University of Singapore Graduate Medical School (Duke-NUS) today announced the start of a Phase I clinical trial of novel cancer drug candidate, ETC-159. This is the first publicly-funded drug candidate discovered and developed in Singapore to advance into first-in-human trials, and will target a range of cancers. Overall, cancer is the leading cause of death in Singapore, accounting for 30 percent of deaths in 2013. Cancer has also resulted in 8.2 million deaths world-wide .

ETC-159 targets a number of cancers including colorectal, ovarian and pancreatic cancers which contribute to a significant proportion of Singapore's cancer burden. These cancers are linked to a group of cell signalling pathways known as Wnt signalling, that have been identified to promote cancer growth and spread when elevated or dysregulated. As ETC-159 is an inhibitor of these pathways, it could suppress cancer proliferation and prevent cancer progression.

This drug candidate therefore offers a promising novel and targeted cancer therapy that could shape future cancer therapeutic strategies.

ETC-159 was discovered and developed through a collaboration between A*STAR's Experimental Therapeutics Centre (ETC), Drug Discovery and Development (D3) unit and Duke-NUS since 2009. This was based on the discovery work of Prof David Virshup from Duke-NUS, who has continued to contribute to the development of the drug candidate.

The Phase I clinical trial will evaluate the safety and tolerability of ETC-159 in advanced solid tumours of up to 58 patients. The first patient was dosed on 18 June 2015.

Dr Benjamin Seet, Executive Director of A*STAR's Biomedical Research Council, said, "This breakthrough, which closely follows local company MerLion Pharmaceuticals' recent success in obtaining FDA approval for one of its drugs, marks an inflection point in Singapore's biomedical sciences initiative. Despite the protracted process of drug discovery and development, I am confident that we will see more locally developed drugs in the pipeline being tested and implemented."

Prof Ranga Rama Krishnan, Chairman of the National Medical Research Council (NMRC), Singapore, said, "The first dosing of a drug developed by A*STAR based on a scientific discovery by Duke-NUS researchers, is an example of the terrific and exciting progress that has been made when different entities come together to work on a common problem. This will lead to developing new treatments that can benefit patients in Singapore and beyond."

Prof Alex Matter, Chief Executive Officer of ETC and D3 said, "The discovery and subsequent development of this drug candidate marks a major breakthrough in cancer therapeutics. It also demonstrates the world-class drug discovery and development capabilities we have built up at ETC and D3, complemented by valued partners like Duke-NUS. We will continue to strengthen these capabilities and partnerships to continue developing a pipeline of promising drug candidates and advancing them into the clinic."

Prof David Virshup, inaugural Director of the Programme in Cancer and Stem Cell Biology at Duke-NUS, said, "As the drug candidate provides a targeted cancer therapy, it could potentially minimise side effects and make cancer treatments more bearable for cancer patients. This is a major milestone that was made possible by Singapore's ongoing investment in basic and translational biomedical research to address unmet medical needs. It is fitting that Singaporeans might be the first to benefit from this Singapore-developed drug."

A*STAR's ETC and Duke-NUS are the primary drivers of the discovery and development of the drug candidate. D3 joined the collaboration in 2013 to bring the project forward to achieve proof of concept in humans.

D3 has obtained ethics and regulatory approval for this trial from the SingHealth Centralised Institutional Review Board (CIRB) and the Singapore Health Sciences Authority (HSA) respectively. The first two sites for the trial are the National Cancer Centre Singapore (NCCS) and the National University Hospital (NUH), Singapore. Trial sites in the United States will be opened as the trial progresses.

Source:

Biomedical Sciences Institutes (BMSI)

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por cyto às 18:15

Terça-feira, 21.07.15

Isis Innovation, Ludwig Cancer Research announce launch of new cancer immunotherapy spinout

 

Isis Innovation, Ludwig Cancer Research announce launch of new cancer immunotherapy spinout

Published on July 9, 2015 at 7:30 AM 

Isis Innovation, the University of Oxford's technology commercialisation company, and Ludwig Cancer Research are proud to announce the launch of a new spinout company, iOx Therapeutics. iOx Therapeutics will develop a novel cancer immunotherapy discovered through a collaboration between Ludwig Cancer Research and Professor Vincenzo Cerundolo, the director of the MRC Human Immunology Unit within the University of Oxford's Weatherall Institute of Molecular Medicine.

Since 2003, Professor Cerundolo, supported by funding from Ludwig Cancer Research, has led a research team working in collaboration with Professor Gurdyal Besra and Dr. Liam Cox of the University of Birmingham and Professor Richard Schmidt of the University of Konstanz. This team discovered multiple synthetic lipid compounds, now under development by iOx, which activate iNKT cells. A large body of evidence suggests that iNKT cells play an important role in anti-tumour immune responses and could prove highly effective in combination with other immunotherapies.

"Preclinical studies of our iNKT-activating compounds have been extremely promising," said Professor Cerundolo. "We've been able to show that these molecules can halt the progression of tumours in animal models. I am very excited to see them moving toward the clinic, and gratified that our research could prove to be of benefit to cancer patients."

"The new immune checkpoint inhibitors recently approved by regulatory agencies, such as anti-PD-1 antibodies, sabotage the strategies used by tumour cells to suppress the immune system and so induce potent anti-tumour immune responses in many patients," said Dr. Jonathan Skipper, Ludwig's executive director of technology development. "There is good reason to expect that iOX's iNKT agonists could significantly improve these responses, and we look forward to seeing the results of their clinical evaluation."

The company has discussed plans for a first human trial with the UK Medicines and Healthcare products Regulatory Agency. The trial will be run by Professor Mark Middleton, director of the Oxford Experimental Cancer Medicine Centre at Oxford University Hospitals NHS Trust.

Jim Mellon, an Oxford alumnus, has invested in the company through SalvaRx, an oncology-focused investment vehicle that provides capital and drug development expertise to support emerging technologies and companies.

Isis Innovation Head of Technology Transfer, Life Sciences Dr. Adam Stoten said, "The field of cancer immunotherapy is moving forward with unprecedented momentum and we're delighted to support Professor Cerundolo and his team in their goal of finding new and better cancer treatments."

Source:

Ludwig Institute for Cancer Research

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por cyto às 18:00

Sábado, 04.07.15

Nanoparticles packed with chemotherapy drug and coated with chitosan target cancer stem-like cells

 

Nanoparticles packed with chemotherapy drug and coated with chitosan target cancer stem-like cells

Published on July 1, 2015 at 7:35 AM ·

Nanoparticles packed with a clinically used chemotherapy drug and coated with an oligosaccharide derived from the carapace of crustaceans might effectively target and kill cancer stem-like cells, according to a recent study led by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James). Cancer stem-like cells have characteristics of stem cells and are present in very low numbers in tumors. They are highly resistant to chemotherapy and radiation and are believed to play an important role in tumor recurrence. This laboratory and animal study showed that nanoparticles coated with the oligosaccharide called chitosan and encapsulating the chemotherapy drug doxorubicin can target and kill cancer stem-like cells six times more effectively than free doxorubicin.

"Our findings indicate that this nanoparticle delivery system increases the cytotoxicity of doxorubicin with no evidence of systemic toxic side effects in our animal model," says principal investigator Xiaoming (Shawn) He, PhD, associate professor of Biomedical Engineering and a member of the OSUCCC - James Translational Therapeutics Program.

"We believe that chitosan-decorated nanoparticles could also encapsulate other types of chemotherapy and be used to treat many types of cancer."

This study showed that chitosan binds with a receptor on cancer stem-like cells called CD44, enabling the nanoparticles to target the malignant stem-like cells in a tumor.

The nanoparticles were engineered to shrink, break open, and release the anticancer drug under the acidic conditions of the tumor microenvironment and in tumor-cell endosomes and lysosomes, which cells use to digest nutrients acquired from their microenvironment.

He and his colleagues conducted the study using models called 3D mammary tumor spheroids (i.e., mammospheres) and an animal model of human breast cancer.

The study also found that although the drug-carrying nanoparticles could bind to the variant CD44 receptors on cancerous mammosphere cells, they did not bind well to the CD44 receptors that were overexpressed on noncancerous stem cells.

Source:

Ohio State University Wexner Medical Center

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por cyto às 11:21

Sexta-feira, 26.06.15

Vaxon Biotech receives new patent in Japan for cancer vaccine candidates

Vaxon Biotech receives new patent in Japan for cancer vaccine candidates

Published on June 22, 2015 at 9:21 AM ·

The company’s worldwide cancer vaccines patent portfolio, made up of ten patent families, now comprises 24 issued patents

Vaxon Biotech, a company specialized in anti-tumor immunotherapy, today announces that it has been granted a new patent in Japan. This patent (JP application n°2012-502822) covers a series of optimized cryptic peptides to be used in the design of the Vbx-026, a new cancer vaccine for solid tumors.

This patent gives Vaxon exclusive rights in Japan and raises its worldwide portfolio to 24 issued patents.

The patent will support the development of Vbx-026, a vaccine dedicated to the treatment of cancer patients expressing the HLA-A24 molecule. This molecule is widely expressed in the Asian population, mainly in Japan, with more than 40% of the Japanese population expressing HLA-A24. The initiation of preclinical development of the Vbx-026 vaccine is planned for 2016.

“This new patent will strengthen our position in Japan, a promising market for the development of the Vbx-026 vaccine,” said Dr. Kostas Kosmatopoulos, CEO of Vaxon Biotech. “With four cancer vaccines under development, ranging from lead optimization to phase II, we have built a strong patent portfolio and we now cover the three major HLA molecules, corresponding to around 80% of cancer patients.”

Vaxon Biotech develops therapeutic vaccines against cancer, based on its proprietary technology of optimized cryptic peptides, which are protected by ten patent families. All vaccines developed by Vaxon target universal tumor antigens and therefore have wide-ranging applications in cancer treatment.

Vx-001 and Vx-006 are already in clinical trials (Vx-001 in an ongoing randomized phase II trial in eight European countries and Vx-006 in an ongoing phase I trial). Vbx-016 has successfully completed its preclinical development and is ready to enter clinical trials and Vbx-026 is at the final stage of lead optimization.

Vx-001 and Vx-006 can be used for the treatment of patients expressing HLA-A2, the most common HLA molecule in humans (40-45% of the world population). Vx-001 and Vx-006 are fully protected by a total of 17 patents granted in Europe, the US, Canada, China and Japan. These patents belong to four patent families and cover peptide optimization technology, the products derived from this technology and their use. Six of these patents belong to INSERM/IGR and have been licensed to Vaxon Biotech, while the remaining 11 are Vaxon’s own property.

Vbx-016 can be used for the treatment of patients expressing HLA-B7, a common HLA molecule (25% of the population). Vbx-016 is already protected by three patent families. Five patents are already granted in Europe, the US, China and South Korea. Additional patents are still under review. All these patents are Vaxon’s own property.

The global market for cancer vaccines is expected to grow to $4.3 billion (€3.8 billion) by 2019, with a five-year compound annual growth rate (CAGR) of 1.3%. Technological advancements, new product launches and unmet treatment needs are predicted to drive consistent growth in this market for the foreseeable future.

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por cyto às 00:58


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