Most of the “affected” positions (3750) will be in selling, general, and administrative areas. One change already underway at the company is the simplification of its global commercial organisation structure by reducing the number of its sales and marketing regions from five to three. Small countries have also been clumped together in a move that AstraZeneca hopes will optimise its resources by increasing shared services and reducing cost bases.

Another 2200 positions will come from R&D. The statement says, “The R&D function will accelerate its transformation, which the company unveiled in January 2010. Under the new programme announced today, further changes will create a simpler and more innovative R&D organization with a lower and more flexible cost base. Excess capacity in certain R&D functions will be reduced, matching resources to AstraZeneca’s more focused R&D portfolio.”

One of the main focuses for R&D restructuring will be in the company’s neuroscience area. Although AstraZeneca recognises that there is much need in this area for better medicines, it adds that advances have been “elusive”. In response, the company will close one R&D site in Montreal (Canada) and wind down R&D activity at its Södertälje (Sweden) site.

In a more positive note for neuroscience, however, the company added that it will continue to pursue innovation in this area by combining internal expertise with “innovative external science” using a virtual neuroscience Innovative Medicines (iMed) unit. The unit will be made up of around 40–50 AstraZeneca scientists, who will conduct discovery and development externally using a global network of academia and industry.

Martin Mackay, president of Research and Development, AstraZeneca, said: “We’ve made an active choice to stay in neuroscience though we will work very differently to share cost, risk and reward with partners in this especially challenging but important field of medical research,” Martin Mackay, AstraZeneca’s president of research and development, said in the statement. “The creation of a virtual neuroscience iMed will make us more agile scientifically and financially – we will be able to collaborate flexibly with the best scientific expertise, wherever it exists in the world.”

The remaining job cuts will be in operations as AstraZeneca seeks to make its supply chain more efficient. In particular, the company says it will be looking at its support functions.

The restructuring is expected to deliver around $1.6 billion in annual benefits by the end of 2014, but that will be little consolation for those losing their jobs. An article in the Wall Street journal estimates that around 30000 jobs have been lost at AstraZeneca over the past five years.

Today, the FDA approved Kalydeco (ivacaftor) to treat a specific subgroup of patients with cystic fibrosis (CF). Cystic fibrosis is an inherited genetic disease that affects a person’s lungs and other organs and may lead to an early death. What makes the availability of Kalydeco even more unique is that the drug’s developer, Vertex Pharmaceuticals, teamed up with the Cystic Fibrosis Foundation to develop and study the drug.

This success story began in 1989 when a team of researchers, including Francis Collins, now the director of the National Institutes of Health, discovered the gene that is involved in cystic fibrosis. This gene, known as CFTR, plays an important role in producing a protein that regulates the flow of salt and water out of the cells that line the cavities of the body. There are a number of different mutations that can cause the CFTR gene to produce a defective protein. This results in lung congestion and digestive problems.

Kalydeco targets a gene mutation that only occurs in about 4 percent of CF patients. Before using this medicine, doctors will test CF patients to determine whether they have this mutation (many CF patients have already been tested to understand what caused their CF). If the patient is a match, the drug may provide substantial benefits including improved lung function and weight gain.

Patients have played an important role in how new drugs are developed and studied since the HIV/AIDS activists in the 1980s and 1990s. But what the Cystic Fibrosis Foundation pioneered is a new form of patient power that some have called venture philanthropy. The Foundation helped with a portion of the drug’s development costs, provided researchers with useful insights about the CF patient population and helped in the recruitment of study participants – contributions that were critical to quickly bringing the innovative new therapy to patients.

The unique and mutually beneficial partnership that led to the approval of this new therapy for some CF patients serves as a great model for future drug development and patient group collaboration moving forward.

Here’s to innovation and continued cooperation and progress for patients!

This blog was originally published on the FDA blog, FDAVoice

Roche, perhaps, more than any other pharmaceutical company, is banking heavily on the combination of diagnostics and drug development to drive pharmaceutical innovation. In reporting its 2010 results in February 2011, Roche reported that it had 12 new molecular entities in late-stage development, of which six were potential personalized healthcare medicines with planned companion diagnostic tests, which included Zelboraf (vemurafenib) and its companion diagnostic for BRAF mutation-positive metastatic melanoma. FDA approved Zelboraf for treating BRAF V600E mutation-positive, inoperable, or metastatic melanoma and the cobas 4800 BRAF V600 Mutation Test, a diagnostic test developed by Roche, in August 2011.

Earlier this month, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended that Zelboraf be granted full marketing authorization as a monotherapy for treating adult patients with BRAF V600 mutation-positive unresectable or metastatic melanom. The corresponding European Commission decision on the marketing authorization of Zelboraf is expected in February 2012. Marketing authorization submissions for Zelboraf also are under review by health authorities in Australia, New Zealand, Brazil, India, Mexico, Canada, and other countries worldwide.

Roche also is using its diagnostic strategy to support new indications for existing drugs. Last month, Roche reported that the cobas EGFR Mutation Test was CE-marked, an indicator of a product’s conformity with EU requirements, and is now commercially availabile in Europe and other countries that recognize the CE mark. The cobas EGFR Mutation Test is a companion diagnostic to identify patients with non-small-cell lung cancer (NSCLC) who harbor mutations in the EGFR (epidermal growth factor receptor) gene and who may benefit from treatment with anti-EGFR tyrosine kinase inhibitors, such as Roche’ Tarceva (erlotinib). Tarceva, an oral EGFR inhibitor, was first approved in September 2004 to treat locally advanced or metastatic NSCLC after failure of at least one other chemotherapy treatment. It later was approved by the European Commission in September 2011 as a first-line monotherapy in people with locally advanced or metastatic NSCLC with EGFR-activating mutations.

Other companies also are reporting success with certain personalized medicines. In August 2011, FDA approved Pfizer’s Xalkori (crizotinib) for treating locally advanced or metastatic NSCLC that expresses the abnormal anaplastic lymphoma kinase (ALK) as detected by an FDA-approved test. The agency approved the drug along with a diagnostic test for the ALK gene abnormality, Abbott Molecular’s Vysis ALK Break Apart FISH Probe Kit. Up to 7% of those patients with NSCLC, typically patients without a history of smoking, have the gene abnormality.

Although personalized medicines will likely hold only a small part of the overall pharmaceutical market by value and volume in the near term, these successes portend of a changing paradigm in drug development.

In April 2011, the EMA’s Committee for Medicinal Products for Human Use recommended a label update for Biogen and Elan’s multiple sclerosis drug Tysabri (natalizumab). Late in January 2012, the FDA also approved the label change in the US.

Although touted as an effective treatment, Tysabri has also been associated with the risk of developing a serious and, often fatal, brain infection called progressive multifocal leukoencephalopathy (PML). The new label identifies that a certain antibody status (presence of anti-JCV antibodies) is a risk factor for developing PML. A test to detect these antibodies can identify at-risk patients, which is a development that marks a step towards personalised medicine — matching the right treatments with the right patients to maximize therapeutic effect.

In their press statement, Biogen and Elan added that Quest Diagnostics will be producing the STRATIFY JCV Antibody ELISA testing service in the US, which is the first blood test authorised by the FDA for the qualitative detection of JCV antibodies. When used with other clinical data from the patient, the test can help healthcare providers determine the risk for developing PML. Such testing has already been used in Europe since the label was updated last year.

Biogen and Elan have also identified two other PML risk factors: over two years of treatment with Tysabri, and previous treatment with medicines known to weaken the immune system.

Tysabri has had a rickety life. It was voluntarily withdrawn from the US market in 2005 because of concerns over PML, but relaunched in 2006 with a black box warning and a strict monitoring plan. In Europe, Tysabri was approved in 2006 but has been under close scrutiny by the EMA. The EMA has also kept a tight watch and finalised a review of the medicine in January 2010, concluding that the benefits of the medicine outweigh the risks.

As well as improving the safety of patients, the new label could also help to boost Tysabri sales. According to an article by Bloomberg, financial analysts have forecast that Tysabri could see its global sales grow to as much as $3 billion by 2016. Without the label change, the drug may only have seen sales of $1.5 to 2 billion.

The JCV diagnostic test is a good example of how pharma companies can improve their medicines. All drugs, unfortunately, have side effects but a lot can be gained by understanding how those effects occur—and in which patients. Biogen and Elan are not the only companies making efforts to personalise their medicines. As was well publicised last year, Sanofi’s Avastin had its breast cancer indication removed in the US. However, Sanofi is looking hard at the drug in order to evaluate a potential biomarker that could help identify which people might derive more substantial benefit from the drug. Interestingly, Avastin was in the headlines yesterday with Bloomberg running a news piece about how Avastin studies have pointed to potential benefits when used in early-stage breast cancer.

No doubt there is more to come in the world of biomarkers, diagnostics and personalized treatments.

In a rare response to those findings, the Department of Health and Human Services, acting on advice from The National Science Advisory Board for Biosecurity (NSABB) asked the authors of the papers and the editors of the journals to publish the papers in redacted form, where the conclusions would be published, but the methodology would not be made public. HHS also asked that language be added to the publications outlining the goals and potential health benefits of the research and detailing the safety measures taken to protect the laboratory workers and the public. In a press release issued by the National Institutes of Health, the agency said “Recognizing the significant potential benefit of the information about the experimental details to the global influenza surveillance and research communities, the US government is working to establish a mechanism to allow secure access to the information to those with a legitimate need in order to achieve important public health goals. The US government is also developing a proposed oversight policy that would augment existing approaches to evaluating research that has the potential to be misused for harmful purposes.”

The authors agreed to the government’s request, and went a step further. In open letters published in Science and Nature, the authors of the papers jointly called for a 60-day moratorium on the creation of new H5N1 strains, to allow time for public discourse on the merits of the research as well as its risk. In the letter, the authors state: “We recognize that we and the rest of the scientific community need to clearly explain the benefits of this important research and the measures taken to minimize its possible risks. We propose to do so in an international forum in which the scientific community comes together to discuss and debate these issues. We realize that organizations and governments around the world need time to find the best solutions for opportunities and challenges that stem from the work.”

Scientists are divided on whether redaction of the data is really in the public interest. Nonetheless, the willingness to pause for an open discussion about the risks versus benefits of this type of research will go some way towards balancing public safety with public health goals.

As a doctoral student at Harvard Medical School, Moshe Pritsker asked to recreate a method of culturing embryonic stem cells that had been reported by researchers in the United Kingdom. He tried following the steps in a related article but could not get the experiment to work, so he ended up flying to the UK to spend time with the scientists who authored the article to watch how they conducted the experiment. With a first-hand look, Pritsker was able to replicate the method—but not everyone has the resources to fly around the world to get an in-person perspective on a particular lab’s methods.
Based on that experience, Pritsker, along with Nikita Bernstein and Klaus Korak, founded the Journal of Visualized Experiments (JoVE). The site provides step-by-step video demonstrations of experimental techniques and procedures. The site was established in 2006 and today, contains many detailed descriptions of advanced research methods through videos. Each video is published together with a peer-reviewed article to explain the video’s scientific quality, applicability, and technical details.

To date, Harvard, MIT, Yale, Oxford, Cambridge, Max Planck, and others have participated in the online journal. About 50 video articles are published per month.

Although journal articles and training workshops provide scientists with insight into how others do something, not every step comes across. “Even if they had the time, experimenters would probably not bother to document many of these nuances or tricks because they are a personal habit or established practice at the lab they are working at,” says JoVE about why the site is useful.  And yet, “these details can often mean the difference between success and failure,” JoVE adds.

The industry has been talking about the idea of sharing information for some time. JoVE offers a new way to help share best practices and to help train train those new to the laboratory or new to certain manufacturing methods.

On Jan. 4, 2012, the HealthCare Institute of New Jersey (HINJ) published a press release which evaluated the results of the 2011 biopharmaceutical and medical technology economic impact survey, a study (conducted by Deloitte) which concluded that the life-sciences industry continued to make up a key sector of New Jersey’s overall economy.

Although the responses of five fewer companies—24 in the 2010 survey compared to 19 the following year—generated less meaningful findings for the most recent survey, HINJ President and CEO Dean J. Paranicas pointed to the strong continued growth in New Jersey’s bio/pharmaceutical sector. “Although we had 20% fewer companies participating in this year’s survey, those that did supply data demonstrate that the life-sciences industry continues to be a major economic driver in New Jersey,” said Paranicas. “However, New Jersey continues to face stiff competition from around the world and within the US for our industry’s investment. If anything, this data reinforces the need for our leaders in Trenton and Washington to continue to pursue policies that create a more competitive and attractive business climate here, and we look forward to continuing to work with them to achieve this objective.”

The study also cited (factoring in the decrease in participation) a total economic impact from reporting HINJ member companies of $24.2 billion in calendar year 2010, as compared to $29.3 billion in calendar year 2009.

Paranicas went on to laud the recent actions taken by Governor [Chris] Christie and the state legislature to make New Jersey more competitive and attractive for life-sciences investment. They include an aggressive and competitive business recruitment and retention program, adopting the single sales factor as the basis for calculating New Jersey’s corporate business income tax, and enhancing the Business Employment Incentive Program (BEIP) to promote greater private sector collaboration with New Jersey’s universities and colleges.

However, every rose has its thorn. The study pointed out that the number of full-time employees decreased from 55,366 in 2009 to 51,619 in 2010, and capital spending dwindled from $1.5 billion to $0.9 billion during that same span of time. The Whitehouse Station, New Jersey-based Merck & Co. announced the elimination of approximately 13,000 jobs following the second quarter of 2011 as part of a cost-cutting initiative. This continues a workforce-reduction trend for Merck in recent years. According to a July 30, 2011, article from The Wall Street Journal, “[Merck] will have eliminated about 30% of the work force it had at the end of 2009, in the wake of its $41.1-billion acquisition of Schering-Plough.”

This reflects the long-growing trend among the industry’s financially dominant companies. Expansion in the form of mergers and acquisitions (M&A), without a focused emphasis on R&D to maintain and add to a workable pipeline, will enable access to only a finite amount of prosperity constructed on a delicate foundation of borrowed time. Paranicas pointed out that global R&D spending increased by $6.1 billion—one of the factors that has contributed to the continued success of New Jersey’s biopharmaceutical sector, despite some overexpansive M&A miscalculations, and the consequences as a result.

The announcement was a disappointment to those who follow the field of regenerative medicine. Geron was the first to successfully bring a stem cell therapy through the regulatory process and to run an approved embryonic stem cell trial. In addition, the program was started at a time when a ban on federal funding for embryonic stem cell research was in place. As a result, Geron funded its research and the clinical trial through private money, and by funding obtained from the State of California, which stepped in to fund embryonic stem cell research when the federal government would not. Geron’s withdrawal from the field doesn’t signal the end of regenerative medicine, but it’s a setback for those waiting for the field to deliver.

Geron indicated in the press release that it hopes to find a partner to take over its stem cell program, which includes not only its cells for nervous system repair but also therapies in development for heart disease, diabetes, cartilage repair and dendritic cells as an immunotherapy vehicle. However, in these times of reduced R&D spending and wary venture capitalists it may be a hard sell. Everyone else will doubtless be doing the same financial calculations that Geron did when it decided to discontinue the program.

See related articles:

Regenerative Medicine: The Need for a National Strategy

New Challenges for Use of Embryonic Stem Cells

Topical formulations can be used to treat local and systematic indications, offer ease of delivery, facilitate patient compliance, and avoid the problem of first-pass metabolism. Successfully developing a topical formulation requires an understanding of the physiochemical properties, such as release characteristics, composition of the drug-delivery system, and the nature of the drug-delivery vehicle. Manufacturing a semisolid dosage requires implementing a CMC (chemistry, manufacturing, and controls) strategy to ensure stability, photosafety, avoidance of product degradation, and minimization of process impurities. The Pharmaceutical Technology webcast, “Optimizing Topical Drug Formulation and Manufacturing,” provides insight on recent advances in topical drug formulations, the latest regulatory/pharmacopoeial requirements in product quality and product performance, and strategies to optimize manufacturing for topical drug products.

Speakers include: Vinod Shah, PhD, chair of the Special Interest Group, Regulatory Science of the International Pharmaceutical Federation and distinguished pharmaceutical scientist and consultant to the US Pharmacopeia; Majella Lane, PhD, senior lecturer in pharmaceutics at the School of Pharmacy at the University of London; and Michael Lowenborg, R&D manager of formulation and process development at  DPT Laboratories.

Additional information and registration for the webcast may be found here.

The National Institutes of Health recently administered cancer vaccine PANVAC to 26 women with breast or ovarian cancer. PANVAC, a recombinant poxviral vaccine, produces two proteins associated with tumor cells to stimulate the body’s immune system to attack the cancer. During the trial, the median time it took for the breast-cancer patients’ condition to progress was 2.5 months, and the patients’ median survival time was 13.7 months. One breast cancer patient was still alive 37 months later. Median survival for the 14 ovarian-cancer patients was 15 months, and one woman went 38 months before her disease progressed. Although the trial was small and did not include a control group, these results seem encouraging.

Researchers from Oxford University also have attempted to fight cancer with the immune system. A team led by Paul Fairchild, codirector of the Oxford Stem Cell Institute, used stem-cell technology to create new dendritic cells from a patient’s skin. The dendritic cells, which organize part of the body’s immune response, carried the marker Melan A so that they would trigger an attack on melanomas. In the study, the team’s dendritic cells activated immune cells that produce antibodies and those that kill other cells. Previous studies using other dendritic cells had stimulated only part of the immune system.

Both of these techniques are still in their early phases. It will be some time before the studies lead to therapies from which patients can benefit, but they add to our knowledge of cancer and underscore the importance of oncology research. I take encouragement from these early steps, which I hope will inspire other drugmakers to take up the challenge of battling cancer.