New Scientific Publication Highlights Long-Term Survival of Brain Cancer Patients Treated With Peregrine Pharmaceuticals' Cotara(R)

TUSTIN, Calif., Feb 11, 2010 /PRNewswire via COMTEX/ ---- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM) today reported publication of data in the online edition of the journal Current Cancer Therapy Reviews that supports the clinical potential of the company's novel brain cancer agent Cotara(R) for the treatment of patients with glioblastoma multiforme (GBM), the deadliest form of brain cancer.(1) Cotara specifically targets cells at the center of brain tumors, so its radioactive payload is able to kill cancer cells while leaving healthy tissue largely unaffected. Cotara is currently being tested in a Phase II clinical trial in recurrent GBM patients.
The new data from investigators at the Huntsman Cancer Institute at the University of Utah Medical Center and researchers at Peregrine Pharmaceuticals reports on long-term patient follow-up from an earlier Phase I trial in 28 GBM patients with recurrent disease. Data presented from the study showed that seven of 28, or 25% of the patients survived more than one year after treatment and three of the 28, or 10.7% of the GBM patients treated in this study have survived more than five years after treatment, including two patients who have survived more than nine years, a positive finding compared to the 3.4% five-year survival rate from initial diagnosis reported by the U.S. Brain Tumor Registry. Additionally, the median survival time of the 28 patients was 38 weeks, a 58% increase over the historical median survival time of 24 weeks for GBM patients treated with standard-of-care therapy.
"The positive results seen in this trial suggest that Cotara has the potential to be a valuable new therapy for patients with glioblastoma, a devastating disease with few treatment options," said lead author Randy L. Jensen, M.D., Ph.D., a researcher at the Huntsman Cancer Institute and associate professor, Department of Neurosurgery at the University of Utah Medical Center. "Our experience with GBM patients treated with Cotara in this trial showed that it demonstrated superior median overall survival compared to historical data, and resulted in long-term survival for a number of patients, a rare occurrence in this deadly disease. These promising data highlight the importance of completing the current clinical trials to confirm these results and of advancing this promising agent towards possible regulatory approval."
Cotara is currently being studied in a Phase II clinical trial for the treatment of GBM in patients who have experienced a first relapse. Interim data from this study was presented at the XIV World Congress of Neurological Surgery in September 2009. It highlighted 10 GBM patients treated at one of the clinical sites and included follow-up durations ranging from seven weeks to over 73 weeks, showing an interim median recurrence-free survival of 33 weeks and an interim median overall survival of 41 weeks. Patient enrollment in this trial has now passed the half way mark. Patient enrollment was recently completed in a Cotara dosimetry and dose confirmation trial in recurrent GBM patients. Data from this study presented at the Society of Nuclear Medicine 2009 Annual Meeting showed that Cotara appeared to be safe and well tolerated, strongly concentrating in the brain tumor while leaving other organs largely unaffected. A number of patients in this trial have surpassed the median expected survival time for relapsed GBM patients. Patient follow-up is continuing.
"The new data published today reinforces and updates the encouraging results we have reported from all three trials of Cotara in GBM patients," noted Joseph Shan, vice president of clinical and regulatory affairs at Peregrine. "Data from the two current Cotara trials presented at medical conferences last year has shown encouraging signs of efficacy and confirmed the ability of Cotara to specifically deliver high doses of radiation to GBM tumors, resulting in significant anti-tumor effects. We look forward to completing the ongoing trials while we assess a variety of clinical and regulatory options to make Cotara more widely available to patients with this devastating disease."
Senior author Missag H. Parseghian, Ph.D., senior director of research and development at Peregrine added, "In total, more than 65 patients with recurrent GBM have received Cotara in the current and previous clinical studies. Localization and accumulation of the drug to the tumor have been excellent and longer-term survivors (greater than one year from the time of Cotara treatment) have been observed in all of the trials."
Overall, Cotara has been administered to a total of 125 patients with brain, colon or liver cancer. Promising data from these studies support Cotara's ability to specifically target solid tumors and its anti-tumor activity, as well as its acceptable safety profile.
(1) Current Cancer Therapy Reviews, (February) 2010, Clinical Update: Treatment of Glioblastoma Multiforme with Radiolabeled Antibodies that Target Tumor Necrosis, pp.13-18 (6) Authors: Randy L. Jensen, Joseph S. Shan, Bruce D. Freimark, Debra A. Harris, Steven W. King, Jennifer Lai, Missag H. Parseghian
About Cotara(R)
Cotara is an experimental treatment for brain cancer that links a radioactive isotope to a targeted monoclonal antibody designed to bind to the DNA histone complex that is exposed by dead and dying cells found at the center of solid tumors. Cotara's targeting mechanism enables it to bind to the dying tumor cells, delivering its radioactive payload to the adjacent living tumor cells and essentially destroying the tumor from the inside out, with minimal radiation exposure to healthy tissue. Cotara is delivered using convection-enhanced delivery (CED), an NIH-developed method that targets the specific tumor site in the brain. Cotara has been granted orphan drug status and fast track designation for the treatment of glioblastoma multiforme and anaplastic astrocytoma by the U.S. Food and Drug Administration.
About Peregrine Pharmaceuticals
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials for the treatment of cancer and serious viral infections. The company is pursuing three separate clinical programs in cancer and HCV infection with its lead product candidates bavituximab and Cotara(R). Peregrine also has in-house manufacturing capabilities through its wholly owned subsidiary Avid Bioservices, Inc. (www.avidbio.com), which provides development and biomanufacturing services for both Peregrine and outside customers. Additional information about Peregrine can be found at www.peregrineinc.com.
Safe Harbor Statement: Statements in this press release which are not purely historical, including statements regarding Peregrine Pharmaceuticals' intentions, hopes, beliefs, expectations, representations, projections, plans or predictions of the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements involve risks and uncertainties including, but not limited to, the risk that results from larger trials will not be consistent with results experienced in earlier trials. Factors that could cause actual results to differ materially or otherwise adversely impact the company's ability to obtain regulatory approval for its product candidates include, but are not limited to, uncertainties associated with completing preclinical and clinical trials for our technologies; the early stage of product development; the significant costs to develop our products as all of our products are currently in development, preclinical studies or clinical trials; obtaining additional financing to support our operations and the development of our products; obtaining regulatory approval for our technologies; anticipated timing of regulatory filings and the potential success in gaining regulatory approval and complying with governmental regulations applicable to our business. Our business could be affected by a number of other factors, including the risk factors listed from time to time in the company's SEC reports including, but not limited to, the annual report on Form 10-K for the year ended April 30, 2009 and the quarterly report on Form 10-Q for the quarter ended October 31, 2009. The company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. Peregrine Pharmaceuticals, Inc. disclaims any obligation, and does not undertake to update or revise any forward-looking statements in this press release.

MS linked to restricted blood flow in the brain

Scientists have found that around half of patients with a form of multiple sclerosis have a narrowing of the blood vessels in the brain.

nterim findings from University of Buffalo in New York, America, showed that people with MS were more likely to have narrow blood vessels in the brain that restrict blood flow.

It is not known if this condition, known as chronic cerebrospinal venous insufficiency (CCSVI), is a cause of MS but the researchers said it is 'at least an important association'. 

Some patients who have undergone surgery to widen narrowed blood vessels have reported an improvement in symptoms.
Patients groups were cautious and said there is no proof the finding of narrow blood vessels is a cause of the disease.
The findings, published on the University's website, found 56 per cent of patients with MS, mostly the form which has periods of relapse and remittance, had the narrowing compared to one 22 per cent of healthy people.
The full findings are due to be reported at the American Academy of Neurology meeting in April.
Around 100,000 people in the UK suffer from MS, an auto-immune disease which destroys the fatty insulating sheath of myelin that coats nerve fibres in the brain and spinal cord.
It can cause a range of symptoms from mild balance problems to severe disability, speech and swallowing problems.
Dr Doug Brown, biomedical research manager at the MS Society, said: "These results are intriguing but it is important to remember that although people with MS may show evidence of CCSVI in screening studies, there's no proof as yet that this phenomenon is a cause of MS, nor that treating it would have an effect on MS.
"The next step is to determine what this actually means for MS, and an investigation into whether there's any potential therapeutic benefit from treatment will be pivotal for this novel theory."

 

Scientists Pinpoint Area of Brain That Fears Losing Money

Those with damaged amygdala had no aversions to risky gambles, study found

WEDNESDAY, Feb. 10 (HealthDay News) -- Researchers say they've pinpointed the area of the brain responsible for the fear of losing money, a finding that offers insight into human economic behavior.
The neuroscientists concluded that the human aversion to losing money is tied to the amygdala, a structure that registers rapid emotional reactions and plays a role in depression, anxiety and autism.
The study included two people with amygdala damage caused by a rare genetic disease and a control group of volunteers without amygdala damage. All the participants were asked if they were willing to accept a variety of gambles involving small amounts of money.
The two people with amygdala damage accepted risky gambles much more often than those in the control group and showed no aversion to money loss.
"Monetary-loss aversion has been studied in behavioral economics for some time, but this is the first time that patients have been reported who lack it entirely," study first author Benedetto de Martino, a University College, London, neuroscientist who is a visiting researcher at the California Institute of Technology, said in a news release from Caltech.
"We think this shows that the amygdala is critical for triggering a sense of caution toward making gambles in which you might lose," a function that may be similar to the amygdala's role in fear and anxiety, said Colin Camerer, a professor of behavioral economics at Caltech.
"Loss aversion has been observed in many economic studies, from monkeys trading tokens for food to people on high-stakes games shows, but this is the first clear evidence of a special brain structure that is responsible for fear of such losses," he added.
The study appears in this week's issue of the Proceedings of the National Academy of Sciences.

Physical Changes in Brain Linked to Altered Spirituality

Mind-body connection noted after surgical removal of tumors, study found

WEDNESDAY, Feb. 10 (HealthDay News) -- Damage to specific parts of the brain boosted levels of spiritual thinking and feeling in patients, a finding that adds new insight into the connection between religious attitudes and the physical makeup of the mind, researchers say.
The findings, published in the Feb. 11 issue of Neuron, are based on research in patients who had surgery to remove brain tumors.
Previously, "neuroimaging studies have linked activity within a large network in the brain that connects the frontal, parietal and temporal cortexes with spiritual experiences," study author Dr. Cosimo Urgesi, of the University of Udine in Italy, said in a news release from the journal's publisher. "But information on the causative link between such a network and spirituality is lacking."
The researchers studied what happened before and after brain surgery to the levels of "self-transcendence" in patients. The study authors defined self-transcendence as spiritual feeling, thinking and behaviors, and explained that it reflects a sense of oneness with the universe and a decreased sense of self.
According to the report, damage to the left and right posterior parietal regions of the brain led to an increase in self-transcendence. "Damage to posterior parietal areas induced unusually fast changes of a stable personality dimension related to transcendental self-referential awareness. Thus, dysfunctional parietal neural activity may underpin altered spiritual and religious attitudes and behaviors," Urgesi said.
The researchers suggested that the finding could help in the development of treatments for mental illness.
In a statement, Dr. Salvatore M. Aglioti, from Sapienza University of Rome, said that if self-transcendence can change quickly as a result of brain damage, "it would indicate that at least some personality dimensions may be modified by influencing neural activity in specific areas. Perhaps novel approaches aimed at modulating neural activity might ultimately pave the way to new treatments of personality disorders."

Scientists find clue to anxiety drug addiction

* Anxiety drugs work on same pathways as heroin, cannabis
LONDON, Feb 10 (Reuters) - Valium-like drugs use the same potentially addictive "reward pathways" in the brain as heroin and cannabis, scientists said on Wednesday, findings which may help in the search for non-addictive alternative anxiety drugs.
Researchers from Switzerland and the United States found that so-called benzodiazepine drugs, such as Ativan, Xanax and Valium, exert a calming effect by boosting action of a neurotransmitter called gamma-aminobutyric acid (GABA) in the same way as addictive drugs like opioids and cannabinoids.
This in turn activates the gratification hormone, dopamine, in the brain, the scientists said, showing that the same brain "reward pathways" are used by both types of drugs.
The findings may help in developing a next generation of non-addictive benzodiazepines, they wrote in the journal Nature.
Roche's (ROG.VX) drug Valium, known generically as diazepam, is the best known of the benzodiazepine class of drugs, which have dominated the anxiety medicine market since the 1960s.
It and Ativan were among a host of other prescription drugs found in the blood of American pop star Michael Jackson when he died in June last year. [ID:nN08229661].
The study found that benzodiazepines seemed to work by binding to a particular part of the GABA, which the researchers named as the alpha1 sub-unit of the GABA type A receptor.
The findings show that developing similar benzodiazepines that bind to a different part may offer the same drug benefits without the addictive side effects, they said.
A study published earlier this month found that people with higher levels of dopamine in the brain tend to be more prone to addictive behaviour. [ID:nLDE60S1SG]
Drug companies have been trying for some time to develop next-generation benzodiazepines by tweaking their chemical make-up to deliver a more selective effect that avoids unwanted side effects, but it has so far proved an uphill struggle.
German scientists conducting early research into a new compound said last year they thought they may have found a better anxiety drug which could counteract panic attacks without the side effects of existing drugs. [ID:nLF385568]
In 2003 Merck & Co (MRK.N) abandoned work on another potential anxiety drug known as GABA Alpha 2/Alpha 3, after mid-stage clinical trial results were disappointing. (Editing by Jon Boyle/David Stamp)

fMRIs Reveal Brain's Handling of Low-Priority Ideas

ScienceDaily (Feb. 10, 2010) — When we put an idea on the back burner, it goes into a processing area of the brain called the default-mode network. This network enables us to hold the low-priority idea in abeyance until a time when we aren't busy with something else.

"The default-mode network appears to be the brain's back burner for social decision making," said Peter T. Fox, M.D., director of the Research Imaging Institute at The University of Texas Health Science Center at San Antonio. "Usually these back-burner ideas relate to interpersonal interactions and decisions that can't readily be quantified and shouldn't be rushed."
Dr. Fox likened this to putting a computer batch job into background processing to wait until the system is less busy.
Role of genetics
A recently released study from the Research Imaging Institute, the Southwest Foundation for Biomedical Research and other institutions offers evidence that genetics plays a role in this back-burner setup, which has been shown to be abnormal in a variety of psychiatric disorders.
The work was described in the Jan. 18-22 online edition of Proceedings of the National Academy of Sciences (PNAS).
The default-mode network is one of several neural networks that operate whether the mind is at rest or is occupied doing a task. A separate PNAS paper, published in 2009 by Dr. Fox and the same collaborators, presented a strong case that all human behaviors may be properly viewed as cooperative interactions among these networks, Dr. Fox said.
Maps
The newer research estimated the importance of genetic effects on the default-mode network by creating maps of eight anatomically distinct regions within the network. These maps were obtained by functional magnetic resonance imaging (fMRI) studies in 333 individuals from 29 randomly selected, extended-family pedigrees.
Network connectivity and gray-matter density were correlated to genetic factors. "We found that more than 40 percent of the between-subject variance in functional connectivity within the default-mode network was under genetic control," Dr. Fox said.
Based on this information, it is possible new diagnostic tools could be considered for various psychiatric or neurological illnesses, he said.
The study also included collaborators from the Yale University School of Medicine, the University of Oxford in Oxford, U.K., and Imperial College in London, U.K. The project is an outgrowth of longstanding collaborations between the UT Health Science Center and the Southwest Foundation for Biomedical Research using tools for gene discovery. It is also a result of substantial collaborations between the Research Imaging Institute and Oxford to develop novel applications of imaging methods.
Future directions
"One long-term research goal is to test whether other intrinsically connected networks are also under genetic control, which we expect they will be," Dr. Fox said. "We also want to identify the genes that are controlling the default-mode network and other networks, and identify disorders associated with their abnormalities. A final goal is to develop treatment strategies."
Other UT Health Science Center co-authors are Rene Olvera, M.D., M.P.H., of the Department of Psychiatry in the School of Medicine, and Peter Kochunov, Ph.D., and Angela Laird, Ph.D., of the Research Imaging Institute.

Smoking not good for the brain - study

THE tobacco industry worked for two decades to skew research into smoking and Alzheimer's disease, to promote the wrong belief it could prevent the degenerative condition, a review of research has found.
US-based scientists have reviewed more than 40 research papers published since 1984, to highlight those with industry links which also suggested smoking could be good for the brain.
A quarter of the papers were found to have industry influence - either through direct funding or using researchers who were also consultants to the industry or who had other ties.
In many cases these relationships were not disclosed, according to the analysis, which found industry-linked papers dotted through the scientific literature up to 2003.
Professor Jurgen Gotz, from the University of Sydney's Brain & Mind Research Institute, welcomed the review, saying it should help to set the record straight on nicotine's effect on the brain
"There have been many studies looking at the incidence of Alzheimer's disease in general, and dementia in general, and the role of nicotine," Prof Gotz said.
"Some of these studies showed, or claimed to show, that smoking, in a sense, protects from Alzheimer's disease.
"It turns out when one takes these (industry-linked) studies into consideration ... the bottom line is smoking indeed is associated with an increased risk of Alzheimer's disease."
The review, by scientists at the University of California, found the industry-linked papers tended to suggest smoking was either not a risk factor or that it protected against Alzheimer's disease.
The independent studies - which outnumbered the industry-linked studies - showed how smoking posed nearly double the risk of developing the disease.
Studies into tobacco and Alzheimer's got underway in the late 1970s in response to anecdotal reports of lower rates of the condition among older smokers.
The beneficial claim continues to circulate via the internet and occasionally it pops up in the mainstream press - including in a 2008 article published in the US' top selling Oprah Magazine.
Prof Gotz said it was time to end the myth that smoking could be good for the brain.
"This has been disproved both in humans, as studies show, and in animals and cell culture systems," Prof Gotz said.