Pharma News

[GodFather]

Placebo effects of different therapies not identical


Not all placebos are equal, and patients who respond to one placebo don't always respond to others, according to research published July 31 in the open access journal PLOS ONE by Jian Kong from Massachusetts General Hospital, Harvard Medical School and colleagues from other institutions.

The researchers tested the analgesic effects of genuine acupuncture, sham acupuncture and a placebo pill on healthy participants' pain sensitivity. Participants were not told what treatment they were receiving, but were informed that the pill was Tylenol, a well-known painkiller and different schools of acupuncture: electroacupuncture and manual acupuncture (sham acupuncture). A control group received no treatment at all. Shortly before and after each treatment, a warm electrode was placed on participants' forearms and the temperature gradually increased. They were asked to indicate when the heat first became painful and when it became too hot to tolerate to identify pain thresholds and tolerance.

No significant associations were found between participants' responses to the different treatments, suggesting that none of these individuals could be identified as placebo 'responders' or 'non-responders'. However, participants' expectations that the treatment would help relieve pain correlated with their pain thresholds and tolerance.

According to the authors, these and other parameters in their study suggest that responses to a placebo depend on diverse factors including the route of administration (pills or acupuncture), environmental cues, and learning based on verbal suggestions or conditioning. Kong adds, "It implies that placebo responses may not be dependent on stable individual traits but rather are more a characteristic of the circumstances of individuals or a combination of both trait and state."

In addition, they also found subjects' responses to sham acupuncture correlated significantly with their response to genuine acupuncture. This suggest that people who responded to genuine acupuncture were significantly more likely to experience pain relief from sham acupuncture, but the authors clarify that this does not indicate the two are the same. Instead, they suggest that acupuncture may have non-specific pain-relieving effects that may contribute to this observation.

Kong J, Spaeth R, Cook A, Kirsch I, Claggett B, et al. (2013) Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue Conditioning and Their Association. PLOS ONE 8(7): e67485. doi:10.1371/journal.pone.0067485

[GodFather]

AstraZeneca PLC second quarter and half year results 2013


AstraZeneca has announced that the revenue in the second quarter declined by 4 percent at constant exchange rates (CER), as the impact from products with recent loss of exclusivity has moderated from the levels experienced in recent quarters. Revenue for the rest of the portfolio was up 4 percent, fuelled by a double-digit increase from the five growth platforms. The pipeline was further strengthened by the addition of three promising late-stage assets in core therapeutic areas of cardiovascular/metabolism and respiratory diseases.

Pascal Soriot, Chief Executive Officer, commenting on the results, said: "We have made real progress in the second quarter against our strategic priorities despite the anticipated impact on revenue of the loss of exclusivity for some brands. We continue to invest in distinctive science, our pipeline projects, products and key markets and our five key growth platforms delivered a double-digit increase in revenue contribution. Despite the fostamatinib disappointment, the late-stage pipeline in our core therapy areas is growing, and has been further strengthened with the acquisitions of Omthera Pharmaceuticals and Pearl Therapeutics and the recently announced collaboration with FibroGen. In announcing the Cambridge Biomedical Campus as the location of our new UK strategic centre, we also reaffirmed our commitment to invest in research and development productivity."

Revenue for the second quarter was $6,232 million, down 4 percent at CER.

Loss of exclusivity on several key brands accounted for approximately $500 million in revenue decline in the quarter.
Five growth platforms (Emerging Markets, Japan, Brilinta, diabetes franchise and respiratory franchise) contributed more than $400 million in CER revenue growth in the second quarter.

Core operating profit in the second quarter was down 10 percent at CER to $2,056 million.

Core EPS was $1.20 in the second quarter, a 21 percent decline at CER, due to a higher tax rate.

Core EPS in the second quarter 2012 benefited by $240 million ($0.19 per share) due to the tax settlement of a cross border transfer pricing issue.
Reported EPS in the second quarter was $0.66, down 44 percent at CER.

Acquisitions of Omthera Pharmaceuticals and Pearl Therapeutics and the recently announced collaboration with FibroGen add three late-stage assets to the pipeline.

Revenue guidance for the full year unchanged; with investment in growth platforms and acquired development projects, Core operating costs now expected to increase in the range of low-to-mid single digits at CER compared with 2012.

The New Drug Application for Forxiga (dapagliflozin) was filed with the US FDA in July 2013.

The Board has recommended a first interim dividend of $0.90.

About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.

[GodFather]

Scientists discover potential new way to treat anxiety


Chemically modified inhibitors of the COX-2 enzyme relieve anxiety behaviors in mice by activating natural "endocannabinoids" without gastrointestinal side effects, Vanderbilt University scientists will report next week. Endocannabinoids are natural signaling molecules that activate cannabinoid receptors in the brain, the same receptors turned on by the active ingredient in marijuana.

These receptors are also found in the gastrointestinal system and elsewhere in the body, and there is evidence that they play a role in wide range of physiological and pathological processes, in addition to modulating stress and anxiety.

If the "substrate-selective" COX-2 inhibitors developed at Vanderbilt also work in humans without side effects, they could represent a new approach to treating mood and anxiety disorders, the researchers conclude in a paper to be posted online Sunday in the journal Nature Neuroscience.

Clinical trials of some of these potential drugs could begin in the next several years, said Lawrence Marnett, Ph.D., director of the Vanderbilt Institute of Chemical Biology and the paper's co-senior author with Sachin Patel, M.D., Ph.D.

The Vanderbilt scientists are pursuing other potential applications of activating endocannabinoids by substrate-selective COX-2 inhibition, including relieving pain, treating movement disorders, and possibly preventing colon cancer.

"The door is really wide open," said Patel, assistant professor of Psychiatry and of Molecular Physiology & Biophysics. "We've just scratched the surface."

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) relieve pain and inflammation by blocking either or both of the cyclooxygenase (COX) enzymes, which produce pro-inflammatory prostaglandins.

It has been known for several years that COX-2 inhibition also activates endocannabinoids.

Because the "substrate selective" inhibitors developed at Vanderbilt increase endocannabinoid levels in the mouse without blocking prostaglandin production, "we think (they) will not have the gastrointestinal and possibly cardiovascular side effects that other NSAIDs do," said Marnett, University Professor and Mary Geddes Stahlman Professor of Cancer Research.

"We thought we knew everything there was to know about (COX-2 inhibitors) until about five years ago when we discovered the substrate selective inhibition," he added. The approach used by the Vanderbilt team "is a really powerful way to help design the next generation of drugs."

Daniel Hermanson, a graduate student in Chemistry, was first author of the paper. Other co-authors were Nolan Harley, Joyonna Gamble-George, Naoko Brown, Brian Shonesy, Ph.D., Phillip Kingsley, Roger Colbran, Ph.D., and Jeffrey Reese, M.D.

The three-year-long study was supported by National Institutes of Health grants CA089450, GM015431, NS064278, DA031572, HL096967, HL109199, MH063232, NS078291 and MH065215.

[GodFather]

Injectable 'smart sponge' holds promise for controlled drug delivery

Researchers have developed a drug delivery technique for diabetes treatment in which a sponge-like material surrounds an insulin core. The sponge expands and contracts in response to blood sugar levels to release insulin as needed. The technique could also be used for targeted drug delivery to cancer cells.

"We wanted to mimic the function of health beta-cells, which produce insulin and control its release in a healthy body," says Dr. Zhen Gu, lead author of a paper describing the work and an assistant professor in the joint biomedical engineering program at North Carolina State University and the University of North Carolina at Chapel Hill. "But what we've found also holds promise for smart drug delivery targeting cancer or other diseases." The research team includes Daniel Anderson, the senior author and an associate professor of chemical engineering and member of the Koch Institute for Integrative Cancer Research at MIT, and researchers from the Department of Anesthesiology at Boston Children's Hospital.

The researchers created a spherical, sponge-like matrix out of chitosan, a material found in shrimp and crab shells. Scattered throughout this matrix are smaller nanocapsules made of a porous polymer that contain glucose oxidase or catalase enzymes. The sponge-like matrix surrounds a reservoir that contains insulin. The entire matrix sphere is approximately 250 micrometers in diameter and can be injected into a patient.

When a diabetic patient's blood sugar rises, the glucose triggers a reaction that causes the nanocapsules' enzymes to release hydrogen ions. Those ions bind to the molecular strands of the chitosan sponge, giving them a positive charge. The positively charged chitosan strands then push away from each other, creating larger gaps in the sponge's pores that allow the insulin to escape into the bloodstream. In type 1 and advanced type 2 diabetes, the body needs injections of insulin, a hormone that transports glucose - or blood sugar - from the bloodstream into the body's cells.

As the insulin is released, the body's glucose levels begin to drop. This causes the chitosan to lose its positive charge, and the strands begin to come back together. This shrinks the size of the pores in the sponge, trapping the remaining insulin.

While this work created hydrogen ions by using enzymes that are responsive to glucose, the technique could be simplified to target cancers by eliminating the enzymes altogether. Tumors are acidic environments that have high concentrations of hydrogen ions. If the sponge reservoir were filled with anticancer drugs, the drugs would be released when the chitosan came into contact with the hydrogen ions in tumor tissues or cancer cells.

"We can also adjust the size of the overall 'sponge' matrix as needed, as small as 100 nanometers," Gu says. "And the chitosan itself can be absorbed by the body, so there are no long term health effects."

In tests using diabetic laboratory mice, the researchers found the sponge matrix was effective at reducing blood sugar for up to 48 hours. However, the researchers published a separate "smart system" for insulin delivery in May that maintained normal blood sugar levels for 10 days.

"But we learned a lot from the promising 'sponge' research and will further optimize it. Meanwhile, we are already exploring applications to combat cancer," Gu says.

The paper, "Glucose-Responsive Microgels Integrated with Enzyme Nanocapsules for Closed-Loop Insulin Delivery," is published online in ACS Nano. The research was supported by a grant from the Leona M. and Harry B. Helmsley Charitable Trust Foundation, and a gift from the Tayebati Family Foundation.

[GodFather]

New drugs to find the right target to fight Alzheimer's disease

The future is looking good for drugs designed to combat Alzheimer's disease. Ecole Polytechnique Fédérale de Lausanne (EPFL) scientists have unveiled how two classes of drug compounds currently in clinical trials work to fight the disease. Their research suggests that these compounds target the disease-causing peptides with high precision and with minimal side-effects. At the same time, the scientists offer a molecular explanation for early-onset hereditary forms of Alzheimer's, which can strike as early as thirty years of age. The conclusions of their research, which has been published in the journal Nature Communications, are very encouraging regarding the future of therapeutic means that could keep Alzheimer's disease in check.

Alzheimer's disease is characterized by an aggregation of small biological molecules known as amyloid peptides. We all produce these molecules; they play an essential antioxidant role. But in people with Alzheimer's disease, these peptides aggregate in the brain into toxic plaques – called "amyloid plaques" - that destroy the surrounding neurons.

The process starts with a long protein, "APP", which is located across the neuron's membrane. This protein is cut into several pieces by an enzyme, much like a ribbon is cut by scissors. The initial cut generates a smaller intracellular protein that plays a useful role in the neuron. Another cut releases the rest of APP outside the cell - this part is the amyloid peptide.

For reasons not yet well understood, APP protein can be cut in several different places, producing amyloid peptides that are of varying lengths. Only the longer forms of the amyloid peptide carry the risk of aggregating into plaques, and people with Alzheimer's disease produce an abnormally high number of these.

The two next-generation classes of compound that are currently in clinical trials target an enzyme that cuts APP, known as gamma secretase. Until now, our understanding of the mechanism involved has been lacking. But with this work, the EPFL researchers were able to shed some more light on it by determining how the drug compounds affect gamma secretase and its cutting activity.

In most forms of Alzheimer's, abnormally large quantities of the long amyloid peptide 42 – named like that because it contains 42 amino acids – are formed. The drug compounds change the location where gamma secretase cuts the APP protein, thus producing amyloid peptide 38 instead of 42, which is shorter and does not aggregate into neurotoxic plaques.

Compared to previous therapeutic efforts, this is considerable progress. In 2010, Phase III clinical trials had to be abandoned, because the compound being tested inhibited gamma-secretase's function across the board, meaning that the enzyme was also deactivated in essential cellular differentiation processes, resulting to side-effects like in gastrointestinal bleeding and skin cancer.

"Scientists have been trying to target gamma secretase to treat Alzheimer's for over a decade," explains Patrick Fraering, senior author on the study and Merck Serono Chair of Neurosciences at EPFL. "Our work suggests that next-generation molecules, by modulating rather than inhibiting the enzyme, could have few, if any, side-effects. It is tremendously encouraging."

During their investigation, the scientists also identified possible causes behind some hereditary forms of Alzheimer's disease. Early-onset Alzheimer's can appear as early as thirty years of age, with a life expectancy of only a few years. In vitro experiments and numerical simulations show that in early-onset patients, mutations in the APP protein gene modify the way by which APP is cut by the gamma-secretase enzyme. This results in overproduction of amyloid peptide 42, which then aggregates into amyloid plaques.

This research illuminates much that is unknown about Alzheimer's disease. "We have obtained extraordinary knowledge about how gamma secretase can be modulated," explains co-author Dirk Beher, scientific director of Asceneuron, a spin-off of Merck Serono, the pharmaceutical division of Merck KGaA, Darmstadt, Germany. "This knowledge will be invaluable for developing even better targeted drugs to fight the disease."

[GodFather]

Chocolate may help keep brain healthy


Drinking two cups of hot chocolate a day may help older people keep their brains healthy and their thinking skills sharp, according to a study published in the August 7, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study involved 60 people with an average age of 73 who did not have dementia. The participants drank two cups of hot cocoa per day for 30 days and did not consume any other chocolate during the study. They were given tests of memory and thinking skills. They also had ultrasounds tests to measure the amount of blood flow to the brain during the tests.

"We're learning more about blood flow in the brain and its effect on thinking skills," said study author Farzaneh A. Sorond, MD, PhD, of Harvard Medical School in Boston and a member of the American Academy of Neurology. "As different areas of the brain need more energy to complete their tasks, they also need greater blood flow. This relationship, called neurovascular coupling, may play an important role in diseases such as Alzheimer's."

Of the 60 participants, 18 had impaired blood flow at the start of the study. Those people had an 8.3-percent improvement in the blood flow to the working areas of the brain by the end of the study, while there was no improvement for those who started out with regular blood flow.

The people with impaired blood flow also improved their times on a test of working memory, with scores dropping from 167 seconds at the beginning of the study to 116 seconds at the end. There was no change in times for people with regular blood flow.

A total of 24 of the participants also had MRI scans of the brain to look for tiny areas of brain damage. The scans found that people with impaired blood flow were also more likely to have these areas of brain damage.

Half of the study participants received hot cocoa that was rich in the antioxidant flavanol, while the other half received flavanol-poor hot cocoa. There were no differences between the two groups in the results.

"More work is needed to prove a link between cocoa, blood flow problems and cognitive decline," said Paul B. Rosenberg, MD, of Johns Hopkins School of Medicine in Baltimore, who wrote an editorial accompanying the study. "But this is an important first step that could guide future studies."

The study was supported by the National Institute on Aging and the National Heart, Lung, and Blood Institute. The cocoa was provided by Mars Inc.

[GodFather]

Novartis study of Afinitor® in advanced liver cancer does not meet primary endpoint of overall survival

Novartis has announced that results of a global Phase III study showed that Afinitor® (everolimus) did not extend overall survival compared to placebo in patients with locally advanced or metastatic hepatocellular carcinoma (HCC) after progression on or intolerance to sorafenib[1]. Hepatocellular carcinoma, an aggressive and debilitating cancer, is the most common type of liver cancer[2].Novartis will not proceed with regulatory filings of Afinitor in this indication.

"While we are disappointed with these results, Novartis remains committed to studying everolimus through a robust research and development program to address unmet needs in different types of cancer," said Alessandro Riva, Global Head, Oncology Development & Medical Affairs, Novartis Oncology. "To date, Afinitor has proven efficacy in a number of tumor types, including hormone receptor positive advanced breast cancer, advanced pancreatic neuroendocrine tumors and advanced renal cell carcinoma."

The results of the HCC trial do not impact the worldwide approvals of Afinitor for these other indications. Everolimus is also in Phase III development in other diseases, including gastrointestinal and lung neuroendocrine tumors (NET), HER2 positive breast cancer, lymphoma and tuberous sclerosis complex (TSC). Results of these trials are expected during 2014 and 2015.

Study details
The Phase III study, EVOLVE-1 (EVerOlimus for LiVer cancer Evaluation-1), is a randomized, double-blind, placebo-controlled trial examining the efficacy and safety of everolimus versus placebo, plus best supportive care (BSC), in adult patients with advanced HCC whose disease progressed after treatment with or who were intolerant to sorafenib, a targeted therapy[3]. The study results continue to be evaluated and will be presented at an upcoming medical conference.

EVOLVE-1 involved 546 patients and was conducted at 156 sites worldwide. Patients in the trial were randomized (2:1) to receive therapy with everolimus 7.5 mg/day orally plus BSC or placebo plus BSC. The primary endpoint was overall survival. Secondary endpoints included time to tumor progression, disease control rate,time to deterioration of performance status, safety and quality of life[1][3].

About everolimus
Afinitor (everolimus) tablets is approved in more than 100 countries, including the United States and throughout the European Union, in the oncology settings of advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy, and in the United States and European Union for locally advanced, metastatic or unresectable progressive neuroendocrine tumors of pancreatic origin.

Everolimus is approved as Afinitor in the European Union for the treatment of hormone receptor-positive, HER2 negative (HR+/HER2 negative) advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a non-steroidal aromatase inhibitor. In the United States, Afinitor is approved for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2 negative breast cancer (advanced HR+/HER2 negative breast cancer) in combination with exemestane after failure of treatment with letrozole or anastrozole.

Everolimus is also available from Novartis for use in certain non-oncology patient populations under the brand names Afinitor® or Votubia®, Certican® and Zortress® and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Indications vary by country and not all indications are available in every country. The safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world.

About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 131,000 full-time-equivalent associates and operate in more than 140 countries around the world.

1. Data on file.
2. Faloppi L. et al. Evolving strategies for the treatment of hepatocellular carcinoma: from clinical-guided to molecularly-tailored therapeutic options. Cancer Treat Rev. 2011; 37(3):169-77.
3. US National Institutes of Health. Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma (EVOLVE-1). Available at clinicaltrials.gov/ct2/show/NCT01035229?term=EVOLVE-1&rank=1. Accessed August 2013.

[GodFather]

GSK launches $50 million venture capital fund to invest in pioneering bioelectronic medicines and technologies

GlaxoSmithKline has announced the launch of Action Potential Venture Capital (APVC) Limited, a new $50 million strategic venture capital fund that will invest in companies that pioneer bioelectronic medicines and technologies. The fund's first investment will be in SetPoint Medical, a California company considered a trailblazer in creating implantable devices to treat inflammatory diseases.

The fund complements the work of GSK’s Bioelectronics R&D unit, which was established in 2012 after a two-year effort to seek out and engage the most promising researchers in this emerging area of science. The name of the fund comes from electrical signals called action potentials that pass along the nerves in the body. Irregular or altered patterns of these impulses may occur in association with a broad range of diseases.

GSK believes that miniaturised devices, or bioelectronic medicines, can be designed to read these patterns. The devices could be designed to interface between the peripheral nervous system and specific organs to read, change or generate electronic impulses that help treat disorders as diverse as inflammatory bowel disease or rheumatoid arthritis; respiratory diseases such as asthma and COPD and metabolic diseases including Type 2 diabetes.

The field of bioelectronic medicines is in its very early stages. GSK's ambition, through collaboration with scientists globally, is to have the first medicine that speaks the electrical language of our body ready for approval by the end of this decade.

"We want to help create the medicines of the future and be the catalyst for this work," said Moncef Slaoui, chairman of R&D and architect of GSK's early stage investment strategy. "GSK can play the integrating role that is needed to drive this new type of medical treatment all the way from the bench to the patient and this fund is a key part of our efforts."

Action Potential Venture Capital intends to build a portfolio of five to seven companies over the next five years. The fund will focus investments in three areas:

New start-up companies that aim to pursue the vision of bioelectronic medicines
Existing companies with technologies that are interacting with the peripheral nervous system through first-generation devices that can stimulate or block electrical impulses
Companies advancing technology platforms that will underpin these treatment modalities

Action Potential Venture Capital will be based in Cambridge, Massachusetts and managed by a small, dedicated team. The fund has named Imran Eba as its first partner. Imran will move from GSK's Worldwide Business Development organisation and work closely with the Bioelectronics R&D unit.

Taking a three-pronged approach to bioelectronics research
GSK's Bioelectronics R&D unit will be supporting the development of a new bioelectronics research community in three ways over the coming months.

In addition to working with the new venture fund, the unit is in the process of offering up to 20 new exploratory research grants and creating a network of investigators. Discovery work has begun on the relationship between the nerves in the body and a range of diseases; the particular pattern of impulses along these nerves; and new technologies that can interface with individual nerve fibres. The unit is also seeking to integrate a broader research community and is engaging with other major funding and research organisations interested in the field. This broader community will be invited to meet at customised summits, including the first global summit to be announced shortly, where Bioelectronics R&D is committed to launching a million dollar innovation prize.

"The Action Potential Venture Capital fund is the third strand in our approach to galvanising a new research community," Imran said. "Together, these three mechanisms will contribute to bolster an ecosystem in which exploratory research as well as product translation is supported, and from which we expect a major wave of new medicines to emerge and benefit patients in future decades."

First APVC investment in SetPoint Medical
GSK's first investment will be in SetPoint Medical, based in Valencia, CA. SetPoint is developing a highly novel and potentially transformative approach to treat inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, by using implantable devices that stimulate the body's vagus nerve. The treatments have been developed based on new understanding that the immune system can be influenced by the nervous system; inflammatory diseases were previously thought to be accessible only by molecular medicines.

In addition to the novel treatment approach, GSK believes SetPoint's new proprietary miniaturised device has important hallmarks of future bioelectronic medicines. Together, SetPoint's treatment approaches and technology promise to provide alternate, and possibly more precise, ways of treating some major diseases.

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

[GodFather]

Novartis first company accredited with global CEO Cancer Gold Standard

Novartis is the first company to earn global CEO Cancer Gold Standard accreditation by the non-profit organization CEO Roundtable on Cancer, a group of cancer fighting CEOs from a variety of industries, including healthcare. The designation recognizes the company's efforts to provide support to Novartis associates in the prevention, diagnosis and treatment of cancer.

"At Novartis, we believe that everyone should have access to early screening programs and innovative therapies," said Joseph Jimenez, CEO of Novartis. "Our efforts for our associates, which are recognized by this designation, are an extension of our goal to redefine cancer for all patients."

Novartis is passionate about the discovery and development of innovative medicines to help provide a broad range of new therapies and practical solutions to advance care of patients. The company's research is driven by a distinctive scientific and clinical strategy focusing on unmet medical needs and knowledge of disease pathways. The Novartis research strategy leverages biomarkers and targeted drug development focused on individual patients. The company's extensive portfolio of access-to-treatment projects adapts to patients' needs, products, collaborators and countries.

Novartis first achieved CEO Cancer Gold Standard designation in the US, and quickly extended these resources around the world. Since then, the company has offered programs such as:

adding preventive health services in Portugal
a yearlong plan on health promotion and its benefits in the Philippines
regular screenings for colon and breast cancers in Japan and Brazil

The impact has been significant. In fact, through the Novartis cancer screening program alone, the company has already documented cases of early cancer detection among our associates and has been able to offer the kind of support and treatment that helps to change lives. Novartis continues to expand the program to leverage the company's internal expertise and expand our cancer network and resources to support employees and their families with the best medical, emotional and physical support possible.

The CEO Roundtable on Cancer was founded in 2001, when former President George H.W. Bush challenged a group of executives to "do something bold and venturesome about cancer within your own corporate families." The CEOs responded by creating and encouraging the widespread adoption of the CEO Cancer Gold Standard which calls for organizations to evaluate their health benefits and workplace culture and take extensive, concrete actions in five key areas of health and wellness to fight cancer in the workplace.

About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 131,000 full-time-equivalent associates and operate in more than 140 countries around the world.

[GodFather]

Preclinical tests may lead to new approach to treat CNS lymphoma

A drug recently approved for use in multiple myeloma is now being tested for its ability to fight central nervous system (CNS) lymphoma, a deadly cancer of the immune system that can affect the brain, spinal cord and fluid, and eyes. The clinical trial, now open at the three campuses of Mayo Clinic - in Florida, Minnesota and Arizona - follows successful testing of the drug, pomalidomide, in mouse models of CNS lymphoma. Details of the preclinical testing are available in the science journal PLOS ONE.

Approximately 5,000 patients are diagnosed with the disease every year in the United States.

"We believe pomalidomide could be beneficial in patients with this cancer because it does two things that most anti-cancer drugs do not do," says Han Tun, M.D., an oncologist at Mayo Clinic in Florida. "The drug has excellent brain penetration, which is a requirement in treatment of brain tumors. The other interesting thing is that it is not only active directly against lymphoma cells but also alters the tumor microenvironment."

Dr. Tun is the senior investigator of the PLOS ONE study and the principal investigator for the clinical trial, which is accruing patients.

"Our preclinical study suggests pomalidomide is very promising. Treatment with pomalidomide in mouse models for CNS lymphoma significantly improved the survival and suppressed the tumor growth," he says. "The phase I clinical trial was developed based on these preclinical results."

Pomalidomide belongs to a class of drugs called immunomodulatory agents. Thalidomide was the first drug in this class and was approved in 2006 for treatment of multiple myeloma, a bone marrow cancer. Pomalidomide was approved for use in multiple myeloma in February.

Study co-authors include five researchers from Celgene, the manufacturer of pomalidomide. Other co-authors are Zhimin Li, Ph.D, Yushi Qiu, M.D., Peng Huang, M.D., Ph.D, David Personett, Brandy Edenfield, and John Copland, Ph.D., all from Mayo Clinic Florida.

Dr. Tun received a grant from Celgene to support this research.