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AMGN - health care reform impact :
"Provisions of the U.S. health-care overhaul law, including one that increases fees paid by drugmakers, cost Amgen $33 million in the first quarter and will increase costs by $200 million to $250 million this year, said George Morrow, the company’s executive vice president for global operations, in a conference call with analysts. The company won’t benefit from greater numbers of Americans being covered by health insurance until 2014, he said."
http://www.bloomberg.com/apps/news?pid=20601202&sid=ahFnRezRZRLQ
The terms nucleotides/nucleosides in #msg-49115388 refer to HCV nucleoside (or nucleotide) polymerase inhibitor not to HIV nucleoside (or nucleotide) reverse transcriptase Inhibitor. Viread is a nucleotide analog.
Erbitux wasn't one of the 4 drugs tested in the BATTLE program but at least one study concludes "In contrast with colorectal cancer, and within the limitations of the data set, efficacy parameters did not appear to correlate with K-Ras mutation status or with any of the EGFR-related biomarkers evaluated. Additional exploratory analyses are essential to identify predictive markers and to optimize patient selection for cetuximab therapy in NSCLC."
http://jco.ascopubs.org/cgi/content/abstract/28/6/918
Edit
Found another:
"Conclusions: These data suggest that KRAS mutations may not play a significant predictive role for cetuximab-based therapy in NSCLC, contrary to colorectal cancer."
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33350
Thanks, Peter. Nature News blog has a topic on AACR with helpful links:
http://blogs.nature.com/news/blog/reports/health_and_medicine/american_association_for_cancer_research/
The BATTLE trial (Biomarker-integrated Approaches of Targeted Therapy for Lung cancer Elimination) produced a lot of buzz at AACR.
Hope for Targeted Lung-Cancer Treatment
http://online.wsj.com/article/SB10001424052748704508904575192051659802366.html?mod=WSJ_latestheadlines
By RON WINSLOW
WASHINGTON—An unusual clinical trial involving four different drugs offered promise that guiding treatment based on the molecular traits of a tumor can improve survival from lung cancer.
Researchers said the study amounted to "proof of concept" for a new approach to clinical trials that could improve the efficiency of cancer-drug development and eventually shorten the time it takes to get new treatments to market.
The study, called Battle, involved 255 patients with advanced lung cancer, an especially lethal disease in which until recently average survival on chemotherapy was about eight months. New drugs, including so-called targeted medicines such as Tarceva, co-marketed by OSI Pharmaceuticals Inc., and Roche Holding AG, have achieved some improvement in survival, but typically in only a fraction of patients.
Doctors don't know which patients are likely to respond to which treatments, resulting in hit-or-miss use of high-cost medicines.
Researchers at the University of Texas M.D. Anderson Cancer Center mounted the Battle trial to see whether matching tumor characteristics called biomarkers with specific drugs would lead to better results. Lung cancer is the leading cancer killer, accounting for 28% of all cancer deaths in the U.S.
The study is too small to call for immediate new treatment strategies. But researchers believe it sets a path for bringing personalized medicine into the care of lung-cancer patients, just as it is already playing a critical role in breast, colon and other tumors.
"This is a first step to find biomarkers that may help supplant existing toxic therapies and to find the right population for a particular drug," said Edward S. Kim, a cancer researcher at M.D. Anderson and principal investigator of the Battle study. He presented results Sunday at the annual meeting of the American Association of Cancer Research.
Key to the study, Dr. Kim said, was the ability to obtain new tumor biopsies from all patients. The samples were analyzed to find molecular traits driving the patients' cancers. Then patients were randomly assigned to one of four drugs: Tarceva; the kidney and liver cancer drug Nexavar from Onyx Pharmaceuticals Inc. and Bayer AG; Zactima, being studied by AstraZeneca PLC for lung cancer; and a combination of Tarceva and Targretin, a drug for lymphoma-related skin problems from Eisai Inc.
Eight weeks after the start of therapy, doctors used imaging to assess whether disease in each patient was under control. Researchers said absence of progression at eight weeks is considered a reliable predictor of overall survival benefit.
After about 40% of the patients were enrolled, researchers looked at the first imaging results to see which combinations of drug and biomarkers were more likely to result in disease control. Then, in a strategy called adaptive trial design, the randomization of the remaining patients was weighted to steer patients toward therapies they were likely to benefit from based on their biomarkers.
The adaptive design is gaining interest among researchers and drug companies because it could help identify drugs that don't work sooner, and identify biomarkers that would be used to enroll patients in late-stage studies required for market approval.
Currently large clinical trials typically take all comers without evaluating their biomarker status. "The problem is that when you take a drug that has a specific target, but you treat everybody, you dilute the effect" of the drug, said Dr. Kim.
Researchers say that is why many targeted cancer drugs fail in late-stage or Phase III studies.
"This is the future," Tyler Jacks, a cancer researcher at Massachusetts Institute of Technology and president of the AACR, said of the Battle trial. "This is how drugs will be developed and clinical trials organized." Just this month, a study called I-Spy-2, led by Laura Esserman, a cancer doctor at University of California, San Francisco, began enrolling patients in a big breast-cancer trial using adaptive design.
In the Battle study, 46% of patients achieved disease control at eight weeks. The improvement was only slightly higher among patients enrolled by the adaptive technique, but researchers said that likely reflected shortcomings in how biomarkers were defined, among other issues.
"We need better biomarkers and better drugs to improve care," said Roy Herbst, an M.D. Anderson researcher and a leader of the Battle study.
Among other findings: Patients whose biomarker status matched up well with the treatment they got had an average survival of 11.3 months compared with just over 7 among those that didn't match well.
Dr. Kim also said Nexavar showed promise in patients whose tumors had a mutation in a gene called KRAS, a particularly troublesome population to treat.
Nexavar also achieved favorable results in patients without a KRAS mutation. Still, said Anil Potti, a lung cancer expert at Duke University Medical Center who wasn't involved with the study, finding an unexpected potential benefit for Nexavar reflects the potential of an adaptive trial to find new drug candidates that might be missed in more conventional trials. Nexavar previously failed to show a benefit in advanced lung cancer in a large trial in which it was combined with chemotherapy.
Dr. Potti and other researchers said the finding suggested the drug might be reconsidered for a lung-cancer study that included KRAS mutations—but that excluded patients with a mutation in a gene governing what is called the epithelial growth factor receptor. Tarceva, confirming other research, worked well in such patients in Battle, but Nexavar didn't.
Among the medicines, only Tarceva is approved for lung cancer in the U.S. The study was sponsored by the U.S. Department of Defense with support from the National Cancer Institute and some pharmaceutical companies.
FRX is in trouble and Savella is certainly not a replacement for Lexapro. Moreover, two of its programs got hit lately - dutogliptin and daxas.
Savella sales in the quarter ended 3/31/10 were $17.4M and $52.7M for fiscal 2010.
http://www.frx.com/news/PressRelease.aspx?ID=1414926
Sales for Savella are projected to be approximately $100M this year.
Acurox's briefing docs imply the upcoming FDA panel will not be positive.
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AnestheticAndLifeSupportDrugsAdvisoryCommittee/UCM209143.pdf
Updated for Tysbari 1Q10 sales as reported yesterday by BIIB:
In the first quarter global sales of Tysabri rose 28 percent to $292 million.
As of the end of March, about 50,300 patients were on commercial and clinical Tysabri therapy worldwide. That compares with a figure of 48,800 patients as of the end of 2009.
http://uk.finance.yahoo.com/news/update-2-biogen-profit-falls-on-charges-tysabri-sales-rise-targetukfocus-e2ed5943dbeb.html
I don't follow GlobeImmune's vaccine program in particular, but l think that using IL28B genotyping as a mean to personalize treatment in hcv is the right approach. Like you said in #msg-49113863
If it were me or someone in my family, I would want to know the genetic profile to ascertain if an EGFr drug was likely to help. Ditto from the various possible chemo regimens.
Here’s HGSI’s PR on the withdrawal of Joulferon/Zalbin MAA for archival purposes (and for the guy who posted the enlightening Housekeeping Note re Press Releases )
Human Genome Sciences Announces Withdrawal of European Marketing Authorization Application For JOULFERON® (ZALBIN) For the Treatment of Chronic Hepatitis C
http://www.hgsi.com/latest/human-genome-sciences-announces-withdrawal-of-european-marketing-authorization-application-for-joulferon-zalbin-for-the-treatment-of-chronic-hepati-3.html
Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced that Novartis has withdrawn a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for approval to market JOULFERON® (albinterferon alfa-2b, known in the United States as ZALBINâ„¢) for the treatment of chronic hepatitis C.
The decision to withdraw the application was based on feedback from European regulatory authorities in preliminary response
to the EMA application, indicating that additional new data would be requested which could not reasonably be generated within the timeframe allowed in the European Centralized Procedure. Feedback included whether the therapeutic benefit offered by JOULFERON dosed once every two weeks is sufficient relative to risk.
ZALBIN (JOULFERON) is being developed by HGS and Novartis under an exclusive worldwide co-development and commercialization agreement entered into in 2006. In November 2009, HGS submitted a Biologics License Application (BLA) to the FDA in the United States for ZALBIN dosed every two weeks, which continues under review. HGS and Novartis are also developing ZALBIN dosed every four weeks, and HGS previously reported the positive interim results of a Phase 2b study of this ZALBIN regimen.
About ZALBIN (albinterferon alfa-2b)
ZALBIN (also known as JOULFERON) is a genetic fusion of human albumin and interferon alfa created using proprietary HGS albumin-fusion technology. Human albumin is the most prevalent naturally occurring blood protein in the human circulatory system, persisting in circulation in the body for approximately 19 days. Research has shown that genetic fusion of therapeutic proteins to human albumin decreases clearance and prolongs the half-life of the therapeutic proteins.
About Human Genome Sciences...
Pharmacogenomic data demonstrating a correlation between GI-5005 treatment effect and polymorphisms in the human IL-28 B gene will also be presented at the EASL meeting on Saturday, April 17 by Dr. McHutchison.
Analysis of Vectibix(R) Study Using New Gene Technology Helps to Advance Prospects for Personalized Medicine
http://www.amgen.com/media/media_pr_detail.jsp?releaseID=1414102
...The analysis used massively parallel, next-generation sequencing technology to investigate whether mutations in nine genes known to be mutated in colorectal cancer, including the previously unanalyzed exon 3 mutation of the KRAS gene, are predictive of response to Vectibix in metastatic colorectal cancer (mCRC).
...In addition to KRAS, mutations in NRAS, another member of the RAS gene family, were also associated with lack of response to Vectibix.
...Observed mutation rates in this study were consistent with previous reports in colorectal cancer; however a higher than expected rate of simultaneous mutation of KRAS and either BRAF or NRAS was observed. Further investigation in larger studies is required to determine the predictive value of BRAF mutations.
The FDA considers ending the Avandia vs. Actos safety study
http://online.wsj.com/article/SB10001424052748704508904575191944217066832.html?mod=WSJ_Pharmaceuticals_leftHeadlines
Novartis has withdrawn its MAA for Joulferon/Zalbin for the treatment of HCV.
http://www.pr-inside.com/human-genome-sciences-announces-withdrawal-r1838886.htm
April 19 (Bloomberg) -- Astellas Pharma Inc. said it won’t raise its $3.5 billion unsolicited bid for OSI Pharmaceuticals Inc. after the target company won approval for expanded use of its main drug.
http://www.bloomberg.com/apps/news?pid=20601202&sid=a6gK1admzZ2Q#
Bapineuzumab - IV every 13 weeks is indeed the less frequent IV dosing but Wyeth/Elan have a subcutaneous formulation (in phase II), which uses weekly injections and Bapineuzumab might end up with this formulation in order to reduce AE.
For the price GENZ charges for these drugs one would expect a more reliable and robust supply, so patients and docs anger is understood and this of course will help Shire and PLX to capture new patients and hold on to switchers.
Yes it's early, the study is small and only looked at Japanese population and further prospective studies are needed. There's no reason to think that IL28B polymorphisms influence the response to telaprevir alone and not other direct antiviral agents. I see that VRUS is looking at IL28B genotype in this PSI-7977 HCV trial and perhaps others will perform retrospective genotype analysis:
http://clinicaltrials.gov/ct2/show/NCT01054729
Btw, it is not yet known how response to IFN sparing STAT-C combo regimens is linked to IL28 polymorphism but it is also very interesting and will probably be studied.
PFE has a similar compound, but I don’t know that program’s status.
Genetic variation near the IL28B gene may also impact telaprevir efficacy:
Amino acid substitution in HCV core region and genetic variation near IL28B gene predict viral response to telaprevir with peginterferon and ribavirin
By Norio Akuta et al.
http://www3.interscience.wiley.com/journal/123333906/abstract?CRETRY=1&SRETRY=0
Abstract
Genetic variation near IL28B gene and substitution of amino acid (aa) 70 and 91 in the core region of HCV genotype 1b can predict the response to pegylated interferon (PEG-IFN)/ribavirin combination therapy, but its impact on triple therapy of telaprevir/PEG-IFN/ribavirin is not clear. The aims of this study were to investigate the predictive factors of sustained virological response to 12- or 24-week regimen of triple therapy in 72 of 81 Japanese adults infected with HCV genotype 1. Overall, sustained virological response and end-of-treatment response were achieved by 61% and 89%, respectively. Especially, sustained virological response was achieved by 45% and 67% in 12- and 24-week regimen, respectively. Multivariate analysis identified rs8099917 near IL28B gene (genotype TT) and substitution at aa 70 (Arg70) as significant determinants of sustained virological response. Prediction of response to therapy based on combination of these factors had high sensitivity, specificity, positive and negative predictive values. Efficacy of triple therapy was high in the patients with genotype TT who accomplished sustained virological response (84%), irrespective of substitution of core aa 70. In the patients having genotype non-TT, those of Arg70 gained high sustained virological response (50%), and sustained virological response (12%) were the worst in patients who possessed both of genotype non-TT and Gln70(His70). In conclusions, this study identified genetic variation near IL28B gene and aa substitution of the core region as predictors of sustained virological response to triple therapy of telaprevir/PEG-IFN/ribavirin in Japanese patients infected with HCV genotype 1b.
D-Pharm's DP-b99 phase III trial in treating acute ischemic stroke got an SPA.
Nature Editorial Published online 14 April 2010
Testing time for gene patents
http://www.nature.com/nature/journal/v464/n7291/full/464957a.html
A surprising US court decision highlights the need to modernize gene-patenting practices if patients are to benefit from advances in genetic research.
The idea of awarding patents for specific gene sequences has been a contentious subject since at least the early 1990s, when it first became technologically possible to generate such sequences in large numbers. But US courts have consistently upheld these patents. Even in Europe, where the practice is particularly controversial, gene patenting has been codified into law since 1998. For better or worse, gene patents had seemed destined to be a settled part of the intellectual-property landscape.
Until 29 March, that is, when the US District Court for the Southern District of New York shocked the biotech community by invalidating patents covering mutations in the BRCA1 and BRCA2 genes that are used to assess the risk of breast and ovarian cancer. Myriad Genetics, a company based in Salt Lake City, Utah, holds exclusive licences on these patents and has aggressively defended them. In 2009, a group of patients, researchers and clinicians sued Myriad, asserting, among other complaints, that the patents hamper medical research. And District Court judge Robert Sweet largely agreed.
Beyond the ruling's power to make headlines, industry observers and legal experts see little chance that it will pose a real threat to gene patents. Not only are US courts outside the boundaries of New York's southern district not compelled to follow Sweet's precedent, but Myriad Genetics has pledged to appeal. The case will next be heard in the Court of Appeals for the Federal Circuit in Washington DC, which many observers feel favours patent holders.
Nevertheless, the decision does reflect growing concern about the impacts of gene patents on genetic testing. As the biotech industry inches closer to the long-anticipated era of personalized medicine, genetic tests promise to exert increasing influence in the clinic. But fully realizing that promise will require a view of gene patenting that is considerably more sophisticated than the one-size-fits-all standard that now prevails.
Genetic testing is undergoing a revolution. Classic tests relying on mutations in one or two genes, such as the BRCA1 and BRCA2 tests, are giving way to complex analyses involving many genetic signatures. Tests for a genetic heart condition called long QT, for example, now assay a dozen genes. Eventually, moreover, these complex analyses will themselves give way to whole-genome sequencing. Strict enforcement of single-gene patents in this landscape could ensnare genetic tests in a patent thicket — a tangled web of patents that would have to be negotiated before a given test could be performed. Such a situation threatens to hinder innovation.
There are also legitimate concerns that gene patents can limit patient and researcher access to genetic tests. This need not always be the case: tests for mutations associated with cystic fibrosis are patented, and the patents licensed to many companies. Those companies seem to have managed to turn a profit on the tests without creating a monopoly.
But in light of these concerns, an advisory committee to the US Department of Health and Human Services recently embarked on an analysis of the impact of gene patents on genetic testing. Its report, finalized in February, distinguishes between the use of a gene patent to cover a genetic test — in which the tester simply observes the sequence of a gene — and the use of that patent to protect investment in developing biotherapeutics, when patent holders use genetic information as a platform for invention. Given this distinction and the importance of preserving access to gene tests in the clinic, the committee recommended that gene-patent rights should not be enforced when they are violated in the course of research or genetic testing.
This proposal leaves many details still to be hammered out — and in any case it faces an uncertain future. Health-department secretary Kathleen Sebelius has yet to decide whether to recommend that Congress adopts the changes — and no bill has yet been introduced. But the proposal has already prompted a sharp outcry from biotechnology lobbyists and some members of Congress, who fear that it could hurt the nascent genetic-testing industry. Nevertheless, the advisory committee has provided one way forward. But whichever way they choose, Sebelius, Congress and the biotechnology industry should act without delay, implementing the basic principle of access to valuable genetic information for patients and researchers alike.
A Nature reporter talks to the chief executive of France's national agricultural institute
What it will take to feed the world
http://www.nature.com/news/2010/100414/full/464969a.html
Q: Are GMOs the silver bullets they are often made out to be?
A: It's clear that genetic progress in the past in France and other rich countries accounted for much of the increase in production, so genetics is far from passé; it's still the number-one technique for increasing yields, for example. For Africa to improve its yields, we clearly need new genetically selected varieties, engineered by either genetic modification or classic breeding techniques. For me, GMOs are not a magic bullet, but we should not refuse them a priori. It's critical to look at GMOs on a case-by-case basis. The first generation of genetically modified organisms on the market is not the one that will solve Africa's problems, although one crop, a Chinese GMO cotton that is resistant to bollworm, has proved extremely useful to the population, because it avoids the spraying of dangerous pesticides — the risk–benefit equation is clearly in favour of its use.
We are now at a stage where we have years of extensive research results on the ecological, economic and health aspects of many GMOs. There are GMOs for which the assessment is undisputedly positive, but there are others — in particular some crops engineered to be resistant to this or that herbicide — for which this is not so. For example, some GMOs result in increased use of herbicides, which can lead to concentration of these chemicals in the environment and negative effects. The results are mixed — that's why it is important not to speak of GMOs in general, but case-by-case. Pest resistance is a really promising and important application for genetic selection because there are a lot of health problems in developing countries that have been linked to the spraying of pesticides.
BAX/Gammagard/Alzheimer’s: masterlongevity has mentioned the cost problem, which could be as high as $80k a year for the 400 mg/kg bodyweight every 2 weeks dose. Plasma volume supply is even a bigger problem.
BAX-Gammagard:
How frequent are the infusions?
Agree on the FUDBARS definition. If they have strong evidence against GM plants, they should present it to the public, not criticizing the already overburdened regulatory agencies. Of course there might be some adverse effects but they are negligent compared to the ample supply of food to the growing population. What can regulatory agencies do? Perform their own long term tests? Who is going to finance it? In pharma, the companies conduct follow up studies (phase IV). I have no objection that MON will be asked to do the same, which I think they are doing anyway.
Here's a recent approach from PFE for a possible treatment of female sexual arousal disorder (FSAD). Still in preclinical stage.
Towards treating female sexual dysfunction: Research reveals secrets of female sexual arousal
http://www.eurekalert.org/pub_releases/2010-04/w-ttf041210.php
By using a novel prototype drug, researchers have discovered more about the mechanisms underlying female sexual arousal. These findings are published today in the British Journal of Pharmacology.
A team of researchers based at Pfizer's labs in Sandwich, Kent, found that electrically stimulating the pelvic nerve increases blood flow to the genitalia, and that this effect was enhanced if they also gave a prototype drug (UK-414,495). They believe that the drug acts by blocking the breakdown of an internal chemical messenger that plays a key role in increasing blood flow during sexual arousal.
When women become aroused, blood flow increases to the vagina, labia and clitoris. This causes the organs to swell, and the vagina to relax, as well as increasing vaginal lubrication and the sensitivity of the genitalia.
Female sexual arousal disorder (FSAD) affects up to 40% of women irrespective of age. These women find that their genital organs do not respond to sexual stimulation, they find arousal difficult and this causes them to become distressed.
"Before this work, we knew surprisingly little about the processes that control all of these changes," says the lead researcher in the project Chris Wayman. "Now we are beginning to establish the pathways involved in sexual arousal scientists may be able to find ways of helping women who would like to overcome FSAD."
This is early stage research involving experimental studies using an animal model of sexual arousal. In it researchers stimulated the pelvic nerve and measured changes in genital organs. They believed the genital arousal occurred because stimulation of the nerve triggered the release of vasoactive intestinal peptide (VIP), a well-known neurotransmitter. VIP has only a short-lived effect, because it is soon broken down by an enzyme called Neutral Endopeptidase (NEP). The researchers believe that their prototype drug increased the arousal because it blocked NEP's ability to break down VIP, therefore letting the VIP have a more powerful and prolonged effect increasing arousal.
The results look all the more exciting because, while the drug did increase the level of sexual arousal, it didn't affect arousal in the absence of stimulation or the rest of the body's cardiovascular system. This suggests that this sort of drug would have a good chance of being safe to use in women, and would only work when combined with sexual stimulation.
"While the particular chemical compound studied in this research did not prove appropriate for further development, the implications of the research could lead to the development of a product in future, although Pfizer has no current plans to develop medicines for FSAD," added Wayman.
A very interesting broader look at disease state from The Scientist:
Top killers share genes
Posted by Megan Scudellari, 12th April 2010
Cancer, obesity, and even atherosclerosis share a common set of differentially expressed genes, suggesting a diverse number of human diseases share the same disrupted biological pathways, according to new research published this week in Cancer Cell.
The genetic link also suggests that drugs currently used for the treatment of metabolic and cardiovascular diseases might also be used against cancer, researchers say.
"In any year, there are probably ten big papers in a field that help push a concept forward," said Reuben Shaw, an HHMI investigator at the Salk Institute in California who was not involved in the research. "I think this is one of them."
Kevin Struhl and colleagues at Harvard Medical School compared the transcription profiles of two genetically identical human mammary epithelial cell lines from the same individual -- one normal and one cancerous, or transformed, through the addition of an oncoprotein -- to determine which genes were differentially expressed in the transformed cells. They then performed the same experiment with human fibroblasts, and juxtaposed the two models to identify 343 genes that were differentially expressed in both models -- a common "cancer gene signature."
"The use of the two systems made a huge difference," said Struhl. With a single model, researchers isolate thousands of genes that appear to be expressed differently in cancerous cells versus normal cells. But by comparing data sets from two totally different cell models, mammary cells and fibroblasts, "it cut down the list of genes from thousands to hundreds. And hundreds is something you can really work with," added Struhl.
Once the team had a list of 343 genes, they set out to identify them. Using basic bioinformatics techniques, they identified several families of transcription factors involved in inflammation and lipid metabolism. "I was completely stunned," said Struhl. A significant amount of research links inflammation and cancer, but the association between metabolic disease and cancer is much less understood. Scanning the literature, the researchers found that many of the 343 genes they implicated in cancer have already been implicated in diabetes, obesity, heart disease, and other top killers.
To validate those metabolic genes that had not previously been linked to cancer, Struhl and his team knocked down the genes prior to transformation and found seven of eleven were important to the development of cancer in both experimental models. In additional work, they demonstrated that low-density lipoprotein (LDL) and its receptor (OLR1), both highly involved in atherosclerosis, also play a role in cancer. "That seems very novel, very unexpected," said Shaw, who studies genes at the interface between cancer and diabetes. "This further illustrates how broadly some of these proteins are involved in different disease states."
Looking at the results, Struhl believes there may be common molecular pathways underlying many disparate diseases. "The idea is that there's essentially a diseased cell state, but the specific phenotype and disease you get depends on what cell type it is," said Struhl. It's a broad idea, he admitted, which may be part of the reason it took him two years to get the paper published.
As a crude test of that idea, the team tested drugs for other diseases -- including metformin (diabetes), celecoxib (arthritis), and simvastatin (atherosclerosis) -- against cancerous cells. "If all these diseases have some common pathways, then drugs against these diseases should also work against cancer," said Struhl. Eleven out of thirteen drugs inhibited cancer development in the cell lines.
The drugs had a dramatic effect on the cancer cells, said Sam Hanash, a molecular diagnostician at the Fred Hutchinson Cancer Research Center who was not part of the study. "The findings are very interesting, and we should give more consideration to those agents in developing strategies for chemoprevention," he said. Last October, Struhl published additional results in Cancer Research demonstrating that metformin selectively killed cancer stem cells in four different types of breast cancer.
"A lot of work is going on concerning the role of metabolism in cancer development," said Hanash. "I think we will see more and more similar studies."
Paper Details:
H.A. Hirsch et al. "A Transcriptional Signature and Common Gene Networks Link Cancer with Lipid Metabolism and Diverse Human Diseases," Cancer Cell, 17(4):348-61, 2010.
http://www.cell.com/cancer-cell/abstract/S1535-6108(10)00069-3
I didn't like the Globes piece and changed the post to the Mersana PR. Have another look.
Mersana Enters Research and Exclusive License Agreement with Teva Pharmaceuticals for the Development and Commercialization of XMT-1107
http://www.prnewswire.com/news-releases/mersana-enters-research-and-exclusive-license-agreement-with-teva-pharmaceuticals-for-the-development-and-commercialization-of-xmt-1107-90730659.html
- XMT-1107 is a novel anti-angiogenic agent that employs Mersana's Fleximer® polymer platform -
CAMBRIDGE, Mass., April 13 /PRNewswire/ -- Mersana Therapeutics, a platform-based cancer therapeutics company, today announced that it has entered into a research and exclusive license agreement with Teva Pharmaceutical Industries Ltd. to develop and commercialize XMT-1107, a novel fumagillin analog, for the treatment of all indications, including cancer. Mersana plans to initiate a Phase 1 clinical trial for XMT-1107 in the second quarter of 2010. XMT-1107 will be the company's second oncology product to enter the clinic. Mersana's XMT-1001, a conjugate of Fleximer and camptothecin (CPT), is currently completing a Phase 1 study.
Under the terms of the agreement, Teva will receive an exclusive license to XMT-1107 for all indications worldwide, excluding Japan, for which Mersana will retain rights. Mersana will be eligible to receive up to $334 million if all development, regulatory and commercial milestones are met across several indications. In addition, Mersana will be eligible to receive royalties on net sales worldwide. Teva will cover all development costs for XMT-1107, excluding those specific to Japan.
"We are very pleased to enter into this partnership with Teva as it not only provides the necessary resources for XMT-1107 to achieve broad therapeutic potential but also validates our Fleximer platform as a means to generate novel products," said Julie Olson, Ph.D., President and CEO of Mersana. "We have now produced two clinical-stage oncology products and look forward to progressing our lead program, XMT-1001, beyond Phase 1 studies and to further expanding our Fleximer-based siRNA delivery program."
"Our agreement with Mersana is yet another example of Teva's commitment to early-stage partnering as a means to enhance our innovative pipeline," said Dr. Aharon Schwartz, Vice President of Teva Innovative Ventures. "We have been impressed by Mersana's success with the Fleximer technology and the potential of XMT-1107. With a focus on oncology, auto-immune and neurology, Teva, through its Innovative Ventures group, seeks partnerships with companies and academia to develop new specialty medicines."
About XMT-1107
XMT-1107 is a conjugate of Fleximer and a novel analog of fumagillin, an angiogenesis inhibitor with a mechanism of action distinct from agents that principally target vascular endothelial growth factor (VEGF). Fumagillin analogs had been shown to have anti-tumor activity in Phase 1 and 2 trials, but development was discontinued due to pharmacokinetic (PK) issues and reversible central nervous system (CNS) toxicity observed in patients. XMT-1107 has been demonstrated, in preclinical pharmacology studies, to have a significantly improved PK profile as well as no evidence of CNS toxicity. Additionally, in preclinical models, XMT-1107 has demonstrated efficacy as a single agent and in combination with other agents, including anti-angiogenics.
About Fleximer®
Fleximer is a novel, biodegradable and bio-inert polymer that can be chemically linked to small molecules, biologics and nucleic acids to enhance their pharmacokinetic and safety profiles. Fleximer has been proven to transform existing and experimental agents into new, patentable drugs with superior properties. The Fleximer platform has broad and versatile applications across therapeutic categories and enhances the delivery of small molecule, protein and nucleic acid-based therapeutics.
About Mersana Therapeutics.
Mersana Therapeutics employs its biodegradable polymer platform (Fleximer®) to create new and better medicines. We are advancing our own clinical-stage pipeline of novel compounds with the potential to address multiple oncology indications. The company has also developed a proprietary Fleximer-based siRNA delivery system that is currently in preclinical studies. Mersana Therapeutics has operations in Cambridge, MA and London, England. For more information, visit www.mersana.com.
Elron/Medingo - Rumor was correct:
Roche acquires Medingo Ltd. and expands its position in the growing insulin delivery systems market
http://www.roche.com/investors/ir_update/inv-update-2010-04-13.htm
Depends again on how well can the assay predict the PML risk, but I expect that JCV Ab positive MS patients will not be candidates for 1st line and when/if receive Tysabri will need tight monitoring and perhaps shorter periods of treatment and drug holidays. Good chance that by 2011 this group of patients will have another option after failing ABCRs and before considering Tysabri - Gilenia (FTY720).
On BIIB's Tysabri and the JCV assay
If the test will indeed have compelling predictive value of developing PML, it can make Tysabri the drug of choice for JCV Ab negative MS patients, imo. However, data from STRATIFY1/2 studies are 2+ years away.
You mean because the rates of protocol-defined minor bleeding were higher in the M118 groups due to the vascular access site?
Discontinuation of the lower dose of (50 IU/kg) arm: the study was originally designed to have 150 patients in each arm i.e. total 600, but ended up with just 503 (only 44 patients enrolled in the 50 IU/kg dose arm)
If one carry a known mutation/s the risk is big enough.
Kind of obvious I believe.
Exactly. If you find one of the mutations, you can tell the carrier that s/he has a very significant risk for cancer. If you could not spot a mutation, but you suspect the genetic is there according to family history, you will look further to the next level of possible risk.