If you’re the CEO of Pfizer — which will face generic competition for Lipitor in 2011, and which holds cash and short term investments worth more than $20 billion — here’s how you put it: “The real goal is to grow revenues . . . We are open to opportunities and constantly looking at those which are big, small and in between.”

And: “We are always open to opportunities to enhance licensing, alliances and acquisitions, but whatever we do –- small or large -– has to meet the criteria of shareholder value.”

That, anyway, is what Pfizer CEO Jeff Kindler told the Financial Times.

Speculating on what multi-billion-dollar deal Pfizer’s going to make next — Bristol-Myers! No, ImClone! No, Amgen! — is a favorite parlor game among pharma nerds.

Still, at a time when it’s faddish for pharma leaders to say they prefer a series of smaller, more finely tuned deals, it’s bracing to hear a CEO say the old-school Big Acquisition is still on the table.

Source: The Wall Street Journal

Parkinson’s is characterized by clumps of aggregated proteins inside cells, which suggests underlying problems in protein recycling and waste disposal. The research team thus wanted to decipher how disrupting the process of recycling kills brain cells.

Some inherited forms of the disease have been linked to mutations in the gene for alpha-synuclein or triplications of the gene, which produce either a toxic form of alpha-synuclein or more alpha-synuclein than normal.

During chaperone-mediated autophagy (CMA), certain selected proteins are funneled into lysosomes. In a neuronal cell line, the investigators found that CMA regulated the activity of MEF2D, a transcription factor needed for proper development and survival of brain cells. MEF2D was continuously shuttled to the cytoplasm where it interacted with the chaperone Hsc70 and was degraded. Inhibition of chaperone-mediated autophagy caused accumulation of inactive MEF2D in the cytoplasm.

The research team also observed that MEF2D levels were increased in the brains of alpha-synuclein transgenic mice and patients with Parkinson’s disease. Investigating further, they found that wild-type alpha-synuclein and a Parkinson’s disease–associated mutant disrupted the MEF2D–Hsc70 binding and led to neuronal death.

Thus, chaperone-mediated autophagy modulates the neuronal survival machinery, and dysregulation of this pathway is associated with Parkinson’s disease.

Following the influence of alpha-synuclein on MEF2D may be a way to connect the various genetic and environmental risk factors for Parkinson’s, even if CMA is not the sole mechanism, says senior author Zixu Mao, Ph.D., associate professor of pharmacology at Emory University School of Medicine. “It may be that various stresses impact MEF2D in different ways,” he says. “We think this work provides an explanation that ties several important observations together.”

Researchers from Johns Hopkins University and the University of Alabama, Birmingham were also involved in this study. Their results are published in the January 2 edition of Science.

Source: GEN News

They showed cancer cells were able to recover even after exposure to a chemical cocktail which triggers suicide in normal cells.

The ability may help cancer cells to block the effect of chemotherapy drugs.

The study, by the Chinese University of Hong Kong, appears in the British Journal of Cancer.

Programmed cell suicide - or apoptosis - plays a key role in keeping the body healthy, by ridding it of damaged or defective cells.

If these cells are not destroyed, then they can may continue to divide, developing into a tumour.

The researchers treated human cervical, skin, liver and breast cancer cells each with three different chemicals - jasplakinolide, staurosporine and ethanol - which triggers apoptosis in normal cells.

They wanted to see if cancer cells could survive once they have passed the point of no return for normal cell death.

The researchers found the cancer cells recovered once the chemical cocktail had been removed - even after the cells had passed normal critical checkpoints.

Changing shape

When the chemicals were removed, the cancer cells regained their shape, function and continued to divide.

They only lost the ability to recover once the nucleus at the very heart of the cell containing key genetic material had started to disintegrate - an event right at the end of the normal cell suicide process.

Researcher Professor Ming-Chiu Fung said the study suggested that cancer cells could use this ability to survive assault by chemotherapy drugs.

He said the discovery could potentially help the development of new, more effective anti-cancer drugs.

Dr Lesley Walker, of the charity Cancer Research UK, said: “This eye-opening discovery has created an entire map of new routes to explore in the search for new therapy targets.

“It is an intriguing advance and one that we hope will play a useful part in our efforts to beat cancer.”

Source: BBC NEWS

The letter, posted late Wednesday on the Web site of the Food and Drug Administration, recommends that doctors consider alternatives to Innohep in patients with deep vein thrombosis, life-threatening blood clots in major veins such as in the legs.

The new warning comes after analysis of preliminary data from a study in Europe of patients 70 years old and older–a group often excluded from medical studies–who were diagnosed with deep vein thrombosis and also had failing kidneys.

The study, known by the acronym IRIS, was stopped in February 2008 after 350 of the patients had been followed for three months. By then, 13 percent in the group getting Innohep had died of various causes, versus 5 percent in a comparison group getting heparin, a widely used anticlotting drug.

“There is no clear pattern as to the causes of death,” the FDA said in a statement.

The agency said available data cannot rule out the possibility that patients in the Innohep group suffered another deep vein blood clot or that there was a problem in manufacturing of the drug.

Celgene, based in Summit, N.J., one of the country’s biggest biotech companies, sells Innohep, but it is manufactured by Leo Pharmaceutical Products of Denmark, according to the product’s package insert.

Innohep has been sold in Europe since 1991 and was approved for U.S. sales in 2000. From early 2001 through early 2007, more than 30 million people in 60 countries were treated with the drug, which is injected just under the skin.

The FDA said it had received 383 reports of side effects and complications worldwide, including 96 deaths, as of Oct. 15, 2008.

Late last July, Celgene sent another letter to doctors warning of an elevated risk of death in patients aged 90 and older. The new letter extends the warning to all elderly patients.

The FDA statement Wednesday said the agency has asked the company to revise the package insert, or label, “to better describe the overall study results which suggest that, when compared to (heparin), Innohep increases the risk of death for elderly patients” with failing kidneys.

The agency said it expects to get a final report from the study in January and will complete its review soon after that.

Source: IB Times

The underlying issue is that doctors usually don’t bother to report possible side effects to the FDA, largely because doing so requires lots of paperwork (just what docs need) and it’s often unclear if a drug caused a particular side effect.

Now, the WSJ reports, Pfizer’s funding a pilot project at Brigham and Women’s and Massachusetts General hospitals in Boston that aims to use electronic medical records to make it easier to catch drug safety risks.

The basic idea is pretty simple: Include brief adverse event reports as an option in the normal routine of filling out electronic charts. Serious events are sent automatically to an outside firm (minus personal information that could identify an individual patient), which sends the data to the FDA. Eli Lilly is funding a similar pilot in Indiana.

One internist at the Brigham told the WSJ he had submitted only a half-dozen reports in 32 years of seeing patients because it was such a hassle. Since the study began Dec. 9, the doc has filed at least a dozen. The report pops up when he says he’s stopped a drug because of side effects. He says the process takes 30 seconds or less. “It’s a blink,” he said.

Alongside this bottom-up process, the FDA is also going top down. The agency last year started working with the insurer WellPoint and scouring data from patients with the Medicare drug benefit to try to do a better job of detecting safety risks.

Source: The Wall Street Journal

For a product to be approved under the new rules, the drug should provide evidence of extended survival by at least three months for patients who have fewer than two years to live, NICE stated, specifying that the medication must also be licensed for treating a condition affecting less than 7000 patients in the UK. The agency indicated that it will improve the appraisal process in order to have guidance ready between three and six months following licensing of a drug. The new guidelines will not be retrospective, but will be valid for appraisals of treatments that are already under review by the agency.

Andrew Dillon, NICE chief executive, noted that agency officials are asking their advisors to give “greater weight” to life-extending drug treatments and stated that “the Institute is also conscious of its responsibility to support the development of novel treatments for smaller patient groups that provide innovative benefits over and above existing NHS care.”

Source: FirstWord

However, industry observers suggest that 2008 will also be remembered for delays in the approval process, with deadlines missed on 32 out of 159 applications through October 31, according to the agency. Notable delays included Eli Lilly’s and Daiichi’s Sankyo’s experimental oral antiplatelet agent prasugrel, which an FDA advisory panel is now scheduled to review on February 3, and Takeda’s diabetes drug alogliptin. Last week, the Japanese drugmaker said that the FDA will decide on alogliptin by June 26 after failing to meet a prior deadline of October 27 “due to internal resource constraints.”

John Jenkins, director of the agency’s Office of New Drugs, recently said that the FDA has “been struggling to meet [drug approval] goals for the past several years.” However, Jenkins noted that the agency bolstered its drug division last year with the addition of more than 800 employees, adding that the FDA hopes to be closer to its objective of reviewing 90 percent of drug applications on time in 2009.

Source: FirstWord

HIV-2 infections and HIV-1 Group O infections are predominantly found on the African continent. Some cases of infection with these two types of viruses have also been detected in the U.S.

The MPX test is designed for use with plasma specimens from human donors of whole blood and blood components but not for testing donated source plasma. It is also intended for screening tissue specimens obtained while the donor’s heart is still beating. The assay is not intended for use on specimens from donors whose heart no longer functions or as a diagnostic aid.

The cobas TaqScreen MPX Test runs on the fully automated cobas s 201 System.

Source: GEN News

“The lack of many signals with strong credibility that emerged from our analysis, despite an enormous amount of work in this area over the years, needs careful consideration,” the authors write in a synopsis published online December 30 in the Journal of the National Cancer Institute. “The ability of the candidate gene approach to identify genetic risk factors may have been overestimated.

“Alternatively, the importance of the DNA repair pathway may have been exaggerated. However, there is increasing recognition that genetic risks of cancer conferred by single variants are almost always very modest. This means that even if the DNA repair pathway is essential for carcinogenesis, extremely large-scale evidence would be necessary to establish with high confidence the presence of specific associations.”

The scientists identified 241 previously reported associations between gene variants and the risk of cancer and reexamined these associations from 1,087 data sets. Initially 31 of the 241 associations appeared to be statistically significantly associated with cancer risk in the meta-analysis. Only XRCC1 allele (-77 T>C) and an allele of ERCC2 (codon 751), however, remained statistically significant after the researchers adjusted for multiple comparisons.

Thirtyone nominally statistically significant (i.e., P < .05 without adjustment for multiple comparisons) associations were recorded for 16 genes in dominant and/or recessive model analyses (BRCA2, CCND1, ERCC1, ERCC2, ERCC4, ERCC5, MGMT, NBN, PARP1, POLI, TP53, XPA, XRCC1, XRCC2, XRCC3, and XRCC4). XRCC1, XRCC2, TP53, and ERCC2 variants were each nominally associated with several types of cancer.

Three associations were graded as having strong credibility, another four had modest credibility, and 24 had weak credibility based on Venice criteria.

Requiring more stringent P values to account for multiplicity of comparisons, only the associations of ERCC2 codon 751 (recessive model) and of XRCC1 –77 T>C (dominant model) with lung cancer had P less than or equal to 0.0001 and retained P   less than or equal to 0.001 even when the first published studies on the respective associations were excluded.

Source: GEN News

GlaxoSmithKline’s deal with Actelion valued at CHF 3.3 billion, or almost $3.2 billion, is the front-runner for alliances forged this year. The company put down 4.45% of this headline-making figure, or CHF 150 million, for exclusive, worldwide rights (excluding Japan) to Actelion’s late-stage drug for insomnia. If the treatment successfully completes the recently begun Phase III trials and wins approval, Acetelion will earn CHF 415 million. The clincher will be the further development of this compound in two other indications, with milestones reaching CHF 2.735 billion.

Second place goes to Celgene, which committed to pay Acceleron Pharma $1.87 billion, with $50 million upfront. The agreement covers an early-stage bone loss compound and three discovery programs in the same indication. Another $510 million will come in milestones for the Phase I candidate and $437 million for each of the discovery programs.

The number three spot belongs to Takeda, which paid Amgen $300 million upfront in an alliance worth $1.77 billion. The company gained Japanese rights to 13 Amgen molecules and became Amgen’s global partner for oncology candidate motesanib diphosphate. Phase III development in non-small-cell lung cancer (NSCLC) which was recently suspended due to higher early mortality rates in the study group, with a recommendation for squamous NSCLC patients to get off the drug. The upfront fee represents about 16.9% of the total value, making this one of the sweeter deals given that candidates are already in Phase I and II studies and there is still potential for motesanib diphosphate to be developed for nonsquamous NSCLC.

GSK fills the number four and five positions, investing about $2.85 billion totally in its inflammatory disease programs. The company paid Cellzome $25.31 million, out of a potential $1.45 billion to license candidates directed against seven targets. Cellzome is banking on achieving various development, regulatory, and commercial goals to earn the remaining $207.47 million per program.

Sneaking in another alliance just before year end, GSK agreed to shell out $1.4 billion to Archemix. For an initial fee of $27.5 million, Archemix will discover aptamers against seven targets in inflammatory diseases. Each program carries a milestone-dependent earn out of $200 million.

Source: GEN News