Cancer Clinical Trials and Treatments Late Stage Developments

Six bottles of chemotherapeutic agents for inj...Image via WikipediaFrom FierceBiotech

For the cancer drug research enthusiast, this report might read in places like a special oncology edition of a gun magazine. Indeed, there are plenty of weapons against cancer to read about here. Several of the drugs listed here represent the advancement of relatively new methods of attacking cancer, including "armed antibodies" and cancer-killing viruses.

 In addition, decades of basic research into the molecular drivers of cancer growth are bearing fruit for drug developers. Not only are these companies making progress in clinical trials, they have landed buyout deals and lucrative partnerships. It's also clear that relatively small companies like Aveo Pharmaceuticals and Curis are making inroads along side the big boys like Pfizer and Roche.

There are 10 late-stage drugs listed in this report, but this editor hesitates to call them the "Top 10" only because there are so many variables to consider to rank them in such a way objectively. Yet these 10 drugs have certainly been generating news and, in most cases, lots of interest among investors and the medical community. All of the drugs have reached pivotal trials for at least one type of cancer.
Here's the list in alphabetical order by each drug's most commonly used moniker, whether that is its alphanumeric code name or generic name. As always, please let us know whether you think there are cancer drugs in pivotal trials that you think should have been on this list or ones on this list that shouldn't be.

1. Carfilzomib - multiple myeloma
2. Crizotinib (PF-02341066) - lung cancer
3. GDC-0449 (vismodegib) - basal cell carcinoma
4. OncoVex - advanced melanoma
5. PLX4032 (RG7204) - melanoma
6. Ponatinib - leukemia
7. SGN-35 (brentuximab vedotin) - Hodgkin's lymphoma, anaplastic large cell lymphomas
8. Tivozanib (AV-951) - advanced renal cell carcinoma
9. T-DM1 (Trastuzumab-DM1) - breast cancer
10. XL184 (cabozantinib) -  prostate cancer


Killer E. coli Strain Identified in German Outbreak Through Genomic Sequencing: Life Technologies

These are e Coli.Image via WikipediaAs of June 15, the number of people who were ill due to the outbreak of a new E. coli strain in Europe had reached 3,244, according to the Associated Press (AP). Most of the reports have been in Germany, and 784 of the total had developed a serious complication that could lead to kidney failure. AP reported that 37 people have died in Germany, and one person died in Sweden.

The German government has said that it could be a while before the outbreak could be tracked to its ultimate source. Critics have lost no time carping about the way the crisis has been handled.

While the epidemiology has been cumbersome, the genomic sequencing that characterized the pathogen wasn’t. It took all of three days for teams at the University Medical Centre Hamburg-Eppendorf and BGI (formerly known as Beijing Institute of Genomics) to complete the sequence. The research groups used Life Technologies’ Ion Personal Genome Machine (PGM). Simultaneously, University Hospital of Muenster in Germany and Life Technologies confirmed these results.

SOURCE: http://www.lbl.gov/Publications/Curren...Image via Wikipedia

Information Uncovered by Sequencing

“Bioinformatics analysis revealed that this E. coli is a new strain of bacteria that is highly infectious and toxic,” BGI said in its report, issued on June 2. The bacterium is an enterohemorrhagic E. coli (EHEC) serotype O104 strain, which has never been involved in any E. coli outbreaks before, the institute explained.
Described as super-toxic, the strain has 93% sequence similarity with the enteroaggregative E. coli (EAEC) 55989 strain isolated in the Central African Republic and known for causing serious diarrhea. Furthermore, the scientists reported, it has “acquired specific sequences that appear to be similar to those involved in the pathogenicity of hemorrhagic colitis and hemolytic-uremic syndrome.”
Model of successive binary fission in E. coliImage via Wikipedia
The bacteria also produce extended-spectrum beta-lactamases, enzymes that confer resistance to most beta-lactam antibiotics including penicillins, cephalosporins, and the monobactam aztreonam.
University Hospital of Muenster and Life Technologies further noted that “the bacterium at the root of the deadly outbreak in Germany is a new hybrid type of pathogenic E. coli strain.” Their data reportedly showed the presence of genes typically found in two different types of E. coli: EAEC and EHEC.

The Instrument that Did the Sequencing

The Ion PGM chip-based sequencing technology connects chemical and digital information through the use of semiconductor technology. It uses a parallel array of semiconductor sensors to perform real-time measurement of the hydrogen ions produced during DNA replication.

A high-density array of wells on the ion semiconductor chips provides millions of individual reactors, while integrated fluidics allows reagents to flow over the sensor array. The combination, Life Technologies says, enables the direct translation of genetic information to digital information.
 A close-up of E. Coli 1057:H7Image via Wikipedia
“What’s different about it is that it doesn’t use cameras or lasers,” Life Technologies CEO Mark Stevenson told GEN. “We measure the pH change in each well with a semiconductor chip.”

The E. coli crisis in Germany appears to have provided the proof of principle and a field test with highly visible results for the Ion PGM. Life Technologies acquired the technology when it bought Ion Torrent in 2010 for $375 million in cash and stock. Life Technologies began selling the instrument to the marketplace for less than $100,000, calling it an “easy-to-use, highly accurate benchtop instrument optimal for mid-scale sequencing projects such as targeted and microbial sequencing.”

When Ion Torrent introduced the technology in 2007, it expected the innovation to democratize research, enabling every lab to have a sequencer on its bench. At the time, the company said it had planned to sell the machine for $50,000 apiece—about one-tenth the cost of existing instruments. Ion said that the instrument could perform a single sequencing “run” for about $500 in one hour.

Low-temperature electron micrograph of a clust...Image via Wikipedia

Detection in Food

The availability of new technologies has indeed greatly facilitated the genomic sequencing of this potentially lethal bacterium. Life Technologies has also developed a tool to test foods thought to be associated with the outbreak.

On June 6, shortly after reporting results from its sequencing efforts, the firm reported that it had completed development of a custom assay to detect the bacterium. Shipments of the TaqMan® E. coli O104 detection kit are now in Europe.

“A qPCR-based assay test is the most accurate method to detect harmful food-borne pathogens because a positive result indicates the presence of that particular strain’s DNA in the food sample that is being tested,” explained Nir Nimrodi, head of food safety at Life Technologies.
 Escherichia coli on Macconkey Agar PlateImage via Wikipedia
“It is also the fastest. While traditional laboratory testing methods can take up to 10 days for results, this test can determine the presence or absence of the European pathogen in 10 to 24 hours, depending on the sample type and size.”

It is hoped that the TaqMan E. coli O104 detection kits will provide an answer to the question that has received a variety of answers since the initial E. coli outbreak: Where did it come from? Originally, on May 26, health officials pointed to E. coli-contaminated cucumbers from Spain as culprits, but researchers later concluded that the cucumbers were contaminated with a different strain.

Suspicion then moved to bean sprouts but faded away after it was found that 23 of 40 samples from the suspect farm tested negative. As of June 8, focus had shifted back to cucumbers, as a CUCO (cucumber of unknown country origin) that had sickened a family in eastern Germany was found to be contaminated with the outbreak strain. The cucumber was discovered in the family’s compost, but there is no conclusive evidence that it’s the source.

Then on June 10, Reinhard Burger, president of the Robert Koch Institute, said that even though no tests of the sprouts from the suspect farm had come back positive for the E. coli strain behind the outbreak, an investigation into the pattern of the outbreak had produced enough evidence to indict the sprouts. German authorities said that they haven’t yet been able to resolve how sprouts at a farm became contaminated.
Along the search for clues about the source of the killer E. coli food bug, a restaurant in the northern German town of Luebeck and a festival in the northern city of Hamburg have also come under suspicion. The European Union has sent food safety experts to Germany to help authorities there identify the source of the deadly E. coli epidemic.

Stevenson noted that “a concern for the global healthcare industry is the ability to identify these pathogens as they arise and then be able to detect and screen for them rapidly and inexpensively.” Like with the Ion PGM, as novel pathogens continue to emerge, so will the need for similar disruptive but relatively affordable technologies.
Escherichia coli in Endo's agarImage via Wikipedia

Isocitrate Dehydrogenase of Escherichia coli. ...Image via Wikipedia

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Anacor Pharmaceuticals and Psoriasis Make Strides With Phase IIb Trials

Treatment ladder for PsoriasisImage via Wikipedia Anacor Pharmaceuticals (NASDAQ:ANAC) announced today preliminary results from its Phase 2b trial of AN2728 for the treatment of mild-to-moderate plaque-type psoriasis. The trial enrolled 68 subjects randomized in a 2:1 ratio, AN2728 to vehicle. Subjects treated with AN2728 showed improvement over vehicle at each of the recorded timepoints during the 12-week study period with peak efficacy of 26% occurring after six weeks of treatment with AN2728.

Amgen submits BLA for XGEVA

AMGen Corporate Logo, 1983Image via WikipediaTHOUSAND OAKS, Calif., June 27, 2011 /PRNewswire/ --

Amgen (NASDAQ: AMGN) today announced the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) to expand the indication for XGEVA® (denosumab) to treat men with castrate-resistant prostate cancer to reduce the risk of developing bone metastases. If approved, XGEVA would be the first therapy licensed to prevent or delay the spread of cancer to the bone.

The sBLA submission is based on a pivotal Phase 3 Study ('147) evaluating XGEVA versus placebo in 1,432 men with castrate-resistant prostate cancer. Results of the '147 study demonstrate that XGEVA significantly prolonged bone metastasis-free survival by more than four months compared with placebo (29.5 versus 25.2 months, respectively) in men with castrate-resistant prostate cancer that had not yet spread to the bone.

 Bone metastasis-free survival is a composite measure of the development of bone metastases or death.
"The successful outcome of this study provides clinical evidence supporting the view that tumors activate the RANK Ligand pathway to penetrate bone," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen.  "XGEVA has the potential to become a significant advance for patients with castrate-resistant prostate cancer who currently have no treatment options to help prevent the spread of cancer to their bones."


Pfizer's To Present Lung Cancer Data July 3-7

Image representing Pfizer as depicted in Crunc...Image via CrunchBase Pfizer Inc. will present early and mid-stage data from its lung cancer portfolio, including PF-00299804 (PF-299) an investigational, oral, pan-HER inhibitor;1 and crizotinib, an investigational, oral, first-in-class compound that inhibits the anaplastic lymphoma kinase, or ALK,2 at the International Association for the Study of Lung Cancer’s (IASLC) 14th World Conference on Lung Cancer (WCLC), July 3-7 in Amsterdam, The Netherlands.

“While lung cancer remains a difficult-to-treat disease, we’re learning more about how therapies like crizotinib and PF-299 may be able to specifically target ALK or the HER pathway, respectively, and how this may lead to more rationally selected and personalized therapy,” said Maurizio Voi, MD, Thoracic Tumor Strategy Lead, Pfizer Oncology. “Data being presented show survival outcomes for PF-299 and crizotinib, as well as quality-of-life or patient-reported outcomes after treatment for patients with non small cell lung cancer, which represent important considerations in determining the best treatment option for these patients.”

First Presentation of PF-299 Preliminary Overall Survival Data


GEN | News Highlights:Firms Report Promising Data for Type 1 and 2 Diabetes Candidates at 71st Annual ADA Meeting

Insulin ApplicationImage via WikipediaGEN | News Highlights:Firms Report Promising Data for Type 1 and 2 Diabetes Candidates at 71st Annual ADA Meeting

GEN | Analysis & Insight: Cloud Computing Augments Clinical Trial Process

GEN | Analysis & Insight: Cloud Computing Augments Clinical Trial Process

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    Pharma and biotech companies have so far tended to use cloud computing services for drug development research, not clinical trials. IBM and other smaller tech companies would like to change all that, though. Additionally, applying cloud computing for data analysis to aid patient care is catching on. As cloud computing extends to clinical data analysis, which would be considered private information, security will loom larger as an issue for drug development companies. The benefits of using the cloud to store, manage, and analyze clinical data are similar to those for other drug development work. The cloud offers time on gigantic, dispersed infrastructures on a pay-as-you-go basis. It is estimated that 8–12% of clinical trial costs come from the need to move data around among various trial sites, comparing the data as it is being created, according to Erich Clementi, vp of strategy and GM of enterprise initiatives at IBM. Additionally, for projects that require heavy data crunching, cloud computing enables vast amounts of processing at a lower cost. For example, Jeffrey T. Leek, Ph.D., assistant professor at Johns Hopkins Bloomberg School of Public Health, and colleagues used an internally developed, open-source cloud-computing platform called Myrna for calculating differential gene expression in large RNA sequencing datasets. Running an analysis for a single RNA sequence on one laptop could take up to three weeks to complete, Dr. Leek explained. In contrast, by renting computers for cloud computation services for $65, Dr. Leek said he could get results back in an hour and 45 minutes.  Continued....


Recent News Concerning HPV in Men, HPV is now linked to causing Throat Cancer

Throat Cancer Linked to HPV

A sharp rise in a type of throat cancer among men is increasingly being linked to HPV, the sexually transmitted human papillomavirus that can cause cervical cancer in women.

A new study from the National Cancer Institute warns that if recent trends continue, the number of HPV-positive oral cancers among men could rise by nearly 30% by 2020. At that rate, it could surpass that of cervical cancers among women, which are expected to decline as a result of better screening.

The study is to be presented this week at the annual American Society of Clinical Oncology meeting.

Between 1988 and 2004, the researchers found, the incidence of HPV-positive oropharynx cancers—those that affect the back of the tongue and tonsil area—increased by 225%. Anil Chaturvedi, a National Cancer Institute investigator who led the research, estimates there were approximately 6,700 cases of HPV-positive oropharynx cancers in 2010, up from 4,000 to 4,500 in 2004, and cases are projected to increase 27% to 8,500 in 2020. 

Find out more about HPV  Currently, Merck markets the vaccine Gardisil