Publication of consensus recommendations for the use of positron emission tomography (PET) imaging–with the radiotracer fluorodeoxyglucose (FDG)–in National Cancer Institute trials will go a long way in helping physicians and scientists determine ways to manage cancer and promote drug development in the future. The recommendations, published in the June issue of the Journal of Nuclear Medicine, focus on the practical aspects of FDG PET (patient preparation; image acquisition, reconstruction and analysis; and quality assurance) and provide a valuable reference for incorporating PET into clinical trials.

“There should be less variability in the performance of FDG PET in clinical trials by enacting these recommendations,” explained principal author Lalitha K. Shankar, NCI medical officer at the Cancer Imaging Program. “This would help speed the evaluation of FDG PET as a biomarker. If FDG PET, as is hoped, proves to be a useful biomarker in certain cancers–such as lymphoma, lung and breast cancer among others–this could potentially result in shorter clinical trials in these malignancies and improved therapy for patients with these cancers,” she said. These guidelines, drafted by PET experts at various universities and institutes in the United States and abroad, represent a step toward qualifying FDG PET as a biomarker or biologic indicator to assess cancer treatment response.

“To date, there has been no significant agreement on the best methodology for obtaining or analyzing 18F-FDG PET. Standard protocols needed to be developed so that data about the effectiveness of FDG PET as an indicator of treatment response in patients could be collected and compared,” Shankar added. Publication of the consensus recommendations is the culmination of attempts to reach agreement between physician and scientist members of the imaging community on certain basic issues regarding the acquisition and analysis of these scans, she said.

The recommendations are the result of a workshop sponsored by NCI’s Cancer Imaging Program in Washington, D.C., in 2005. Participants reviewed the status of FDG PET technology and clinical experience in both diagnosis and in monitoring therapeutic response. More recently, NCI, the U.S. Food and Drug Administration and the Centers for Medicare and Medicaid Services entered into a memo of understanding to improve “the clinical utility of biomarker technologies as diagnostic and assessment tools that facilitate the development of safer and more effective cancer therapies.”

“Consensus Recommendations for the Use of 18F-FDG PET as an Indicator of Therapeutic Response in Patients in National Cancer Institute Trials,” appears in the June issue of the Journal of Nuclear Medicine, which is published by SNM. Besides Shankar, co-authors include Daniel Sullivan, Cancer Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Md.; John M. Hoffman, Division of Nuclear Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City; Steve Bacharach, Department of Radiology, University of California, San Francisco; Michael M. Graham, Division of Nuclear Medicine, Department of Radiology, University of Iowa, Iowa City; Joel Karp, Division of Nuclear Medicine, Department of Radiology, University of Pennsylvania, Philadelphia; Adriaan A. Lammertsma, Department of Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, the Netherlands; Steven Larson, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, N.Y.; David A. Mankoff, Division of Nuclear Medicine, University of Washington, Seattle; Barry A. Siegel, Mallinckrodt Institute of Radiology, St. Louis, Mo.; and Annick Van den Abbeele and Jeffrey Yap, Department of Radiology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass.

About SNM
SNM is an international scientific and professional organization of more than 16,000 members dedicated to promoting the science, technology and practical applications of molecular and nuclear imaging and therapy to diagnose, manage and treat diseases in women, men and children. Founded more than 50 years ago, SNM continues to provide essential resources for health care practitioners and patients; publish the most prominent peer-reviewed resource in the field; sponsor research grants, fellowships and awards; host the premier annual meeting for medical imaging; and train physicians, technologists, scientists, physicists, chemists and radiopharmacists in state-of-the-art imaging procedures and advances. SNM members have introduced–and continue to explore–biological and technological innovations in medicine that noninvasively investigate the molecular basis of diseases, benefiting countless generations of patients. SNM is based in Reston, Va.; additional information can be found online at snm//.

Contact: Maryann Verrillo

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A drug used to treat kidney cancer also targets a genetic mutation active in about one third of patients with acute myeloid leukemia (AML), the most common and lethal form of adult leukemia, researchers at The University of Texas M. D. Anderson Cancer Center report in the Jan. 29 edition of the Journal of the National Cancer Institute.

In a Phase I clinical trial, the drug sorafenib reduced the median percentage of leukemia cells circulating in the blood from 81 percent to 7.5 percent and in the bone marrow from 75.5 percent to 34 percent among AML patients whose leukemia includes the FLT3-ITD mutation. Two patients had circulating leukemia cells, or blasts, drop to zero.

“AML patients with this mutation have a particularly poor prognosis, so this highly targeted drug appears to be a significant step forward in leukemia therapy,” says senior author Michael Andreeff, M.D., Ph.D., professor in M. D. Anderson’s Department of Stem Cell Transplantation and Cellular Therapy and Department of Leukemia.

The JNCI paper reports the drug’s effect in lab experiments, a mouse model of the disease, and in a Phase I study of 16 patients with relapsed or resistant AML known to have the FLT3-ITD mutation.

There have been no major side effects in the clinical trial to date, so no maximum tolerated dose has been reached, Andreeff notes. The drug has little effect on cells with normal versions of the gene and does not interfere with normal blood cell formation.

A Phase I/Phase II clinical trial for AML is open at M. D. Anderson that combines sorafenib with the standard of care chemotherapy combination for AML, idarubicin and cytosine arabinoside. Presently, the trial is open for relapsed patients and those newly diagnosed with high-risk disease, says study co-author Jorge Cortes, M.D., professor in M. D. Anderson’s Department of Leukemia. As safety and dose escalation research progress, sorafenib will be made available to other patients and assume a role in frontline therapy.

About 14,000 new cases of AML are diagnosed annually in the United States and the disease kills about 9,000 people each year. AML is characterized by swift proliferation of immature white blood cells in the blood and bone marrow that crowds out normal cells, leaving patients exposed to infection, severe anemia, and bleeding.

While major progress has been made treating some forms of leukemia and lymphoma, acute myeloid leukemia has seen less improvement in recent years. Andreeff says that’s because AML exploits multiple molecular pathways and that these pathways differ from one type of AML to the next.

Andreeff and colleagues have shown that molecular pathways subverted and used by AML collude with each other, so when one pathway is blocked, the others redouble their efforts to fuel the disease.

“Here we have a great response against an important mutation, but sorafenib alone will not cure patients,” Andreeff notes. Combination therapy will be required. Andreeff and colleagues are planning to examine other sorafenib combinations against FLT3-mutant disease.

After in vitro tests showed that sorafenib inhibited the growth of FLT3 mutant leukemia cell colonies, the research team tested the medication in a mouse model of the disease. Sorafenib-treated mice had a median survival of 36.5 days compared with 20.5 days in untreated mice. Bioluminescence imaging showed widespread cancer growth in untreated mice and barely detectable disease in those that had received the drug.

Sorafenib, known commercially as Nexavar® and co-developed by Bayer AG and Onyx Pharmaceuticals, already is approved for advanced renal cell carcinoma and inoperable liver cancer by the U.S. Food and Drug Administration. It is being tested against other solid tumors.

The drug targets both tumor cell growth and angiogenesis new blood vessels woven by cancer to sustain itself – by targeting two classes of kinases, which are enzymes that affect proteins by attaching phosphate groups to them.

Sorafenib’s antileukemia effects appear to be superior to early results of new therapies under development that more narrowly target the FLT3 gene. Andreeff says the drug’s ability to hit multiple kinases probably accounts for this, but the exact molecular mechanisms involved require further study.

Co-authors with Andreeff and Cortes are lead author Weiguo Zhang, M.D., Ph.D., who conducted most of the project’s laboratory research, Marina Konopleva, M.D., Ph.D., Yue-xi Shi, Teresa McQueen, Xiaoyang Ling, Ph.D., all of the department of Stem Cell Transplantation and Cellular Therapy; David Harris, Zeev Estrov, M.D., and Alfonso Quintas-Cardama, M.D. all of the Department of Leukemia; and David Small, M.D. of Johns Hopkins University School of Medicine.

Research was funded by grants from the National Cancer Institute, a Leukemia SPORE Career Development Award, and the Cancer Therapy Evaluation Program.

About the University of Texas M. D. Anderson Cancer Center

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 39 Comprehensive Cancer Centers designated by the National Cancer Institute. For five of the past eight years, M. D. Anderson has ranked No. 1 in cancer care in “America’s Best Hospitals,” a survey published annually in U.S. News and World Report.

University of Texas M. D. Anderson Cancer Center
1515 Holcombe Blvd., Box 229
Houston, TX 77030
United States
mdanderson

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New data demonstrate that GlaxoSmithKline’s (NYSE: GSK) cervical cancer candidate vaccine, CERVARIX provides significant protection for women against the four most common cancer-causing human papillomavirus types for nearly six and a half years, the longest duration of protection reported to date. Over this time, the cervical cancer candidate vaccine showed 100 percent efficacy in preventing precancerous lesions due to cancer-causing virus types 16 and 18 and also provided substantial protection against infection caused by virus types 31 and 45.

These data show that virtually 100 percent of women in the study, 15-25 years of age, maintained high levels of antibodies against both virus types 16 and 18 at every time point for nearly six and half years. This signifies the longest duration of consistently high antibody levels demonstrated by a cervical cancer vaccine. Antibody levels remained several times higher than natural infection levels over the extended period of time.

“With this trial, we continue to see high levels of antibodies that lasted over time in virtually all women studied, which is critical for the prevention of cervical cancer,” said Diane Harper, MD, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, NH. “These data are remarkable as they show the potential for this cervical cancer vaccine to protect women over the long term.”

The study also confirmed substantial cross-protection for nearly six and a half years against incident infection caused by virus types 45 and 31. Specifically, the vaccine showed 78 percent efficacy in preventing incident infection caused by virus type 45, and 60 percent efficacy in preventing incident infection caused by virus type 31.

Virus types 18 and 45 are responsible for a significant percentage of a particularly aggressive and deadly form of cervical cancer known as adenocarcinoma. This type of cervical cancer tends to occur in younger women and is not well detected by routine screening methods.

“We specifically designed our cervical cancer vaccine with the goal of providing long-lasting protection from cervical cancer,” said James Tursi, MD, Director of Medical Affairs, North America, GlaxoSmithKline. “These study results are important because women remain at risk for infection with cancer-causing virus types throughout their lives, and long-term protection will be an essential component of a successful vaccination strategy.”

The results also include safety data from nearly six and a half years, showing that the candidate vaccine had no meaningful differences between the study groups and had a favorable overall safety profile.

These data were presented today at the Society of Gynecologic Oncologists (SGO) annual meeting in Tampa, FL.

About the study

This was an extended follow-up (EFU) analysis of women who participated in the initial efficacy study of GSK’s cervical cancer candidate vaccine. The initial study was a double-blind, controlled trial of 1,113 young women between 15-25 years of age, randomized to receive three doses of the GSK candidate vaccine for cervical cancer formulated with the AS04 adjuvant system, or three doses of placebo on a 0, 1 and 6 month schedule.

This extended follow-up study looked at study endpoints for 776 women from the same cohort of women for a period of up to 76 months. The trial was conducted in 28 centers in Brazil, Canada and the U.S. and evaluated the efficacy, safety and immunogenicity of GSK’s cervical cancer candidate vaccine for the prevention of infection with cancer causing virus types 16 and/or 18, and other cancer-causing virus types, as well as associated Pap smear abnormalities and cervical precancerous lesions. In the extended follow up study, women were evaluated for the presence of human papillomavirus DNA by PCR using cervical samples and annual cervical cytology evaluations were performed. Women were referred for colposcopy following protocol guidelines. Women were also assessed for long-term immunogenicity and safety.

About cervical cancer and its progression

Approximately 100 types of human papillomavirus have been identified to date and, of these, approximately 15 virus types are known to cause cervical cancer. Virus types 16, 18, 45 and 31 are responsible for approximately 80 percent of cervical cancers globally. Infection with cancer-causing virus types can lead to the formation of abnormal cells in the cervix, which, over time, may become precancerous or cancerous. It is a necessary precursor of cervical cancer. Throughout their lifetime, women may be exposed to cancer-causing virus types and are potentially at risk of developing cervical cancer.

Worldwide, more than 500,000 women will be newly diagnosed with cervical cancer and over 280,000 women will die from it each year. In the United States, after breast cancer, cervical cancer is the second leading cause of cancer death in women ages 20 to 39.

About the GSK Cervical Cancer Vaccine

To date, CERVARIX has been approved in 55 countries around the world including the 27 member countries of the European Union, Mexico, Australia, Singapore and the Philippines. Licensing applications have been submitted in 28 additional countries including Japan. GSK also submitted CERVARIX to the World Health Organization (WHO) for prequalification in September 2007.

GSK submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for its cervical cancer candidate vaccine in March 2007.

About GlaxoSmithKline

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. For company information, please visit gsk/media.

GSK Biologicals (GSK Bio), one of the world’s leading vaccine manufacturers, is headquartered in Rixensart, Belgium, where the majority of GlaxoSmithKline’s activities in the field of vaccine research, development and production are conducted. GSK Bio employs more than 1,500 scientists, who are devoted to discovering new vaccines and developing more cost-effective and convenient combination products to prevent infections that cause serious medical problems worldwide. In 2006, GSK Bio distributed more than 1.1 billion doses of vaccines to 169 countries in both the developed and the developing world – an average of 3 million doses a day. Of those vaccine doses, approximately 136 million were doses of combination pediatric vaccines which protect the world’s children with up to six diseases in one vaccine.

References:

1. Harper D, Gall S, t al. HPV-007 Efficacy Abstract. “Sustained Immunogenicity and high efficacy against HPV-16/18 related cervical neoplasia: Long-term follow-up through 6.4 years in women vaccinated with CERVARIX (GSKS HPV 16/18 AS04 Candidate vaccine)” To be presented at: SGO’s Annual Meeting on Women’s Cancer. March 10, 2008 Tampa Convention Center.

2. Wieting S., et al. HPV-013 Month 18 Extension Abstract. Presented at the European Society of Paediatric Infectious Diseases (ESPID) annual meeting on 2-4 May 2007

3. GSK Data on File

4. Schuind A. HPV-007 Final Analysis. To be presented at: SGO’s Annual Meeting on Women’s Cancer. March 10, 2008

5. Bulk S, Berkhof J, Bulkmans NW, et al. Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands. Br J Cancer. 2006;94:171-175.

6. Liu S, Semenciw R, et al. Cervical cancer: the increasing incidence of adenocarcinoma and adenosquamous carcinoma in younger women. CMAJ 2001; 164: 1151-1152.

7. Harper DM, Franco EL et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from aluminium control trial. The Lancet 2006; 367: 1247-1255.

8. Gall, S., et al. Sustained Efficacy up to 5.5 years in women vaccinated with an AS04 Adjuvanted HPV 16/18 L1 VLP Vaccine. Presented at AACR Medical Meeting. April 17, 2007

9. Gravitt PE, Jamshidi R. Diagnosis and management of oncogenic cervical human papillomavirus infection. Infect Dis Clin North Am, 2005; 19:439-458

10. Mu?±oz N, Bosch FX, de Sanjose S,et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348: 518-527

11. Mu?±oz N, Bosch FX, Castellsague X et al. Against which human papillomavirus types shall we vaccinate and screen? The international perspective. Int. J. Cancer 2004; 111; 278-285

12. Harper DM, Franco EL, et al, for the GlaxoSmithKline HPV Vaccine Study Group. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomized controlled trial. Lancet 2004; 364: 1757-1765.

13. Baseman JG, Koutsky LA. The epidemiology of human papillomavirus infections J Clin Virol 2005; 32 Suppl 1; S16-24

14. World Health Organization. Initiative for Vaccine Research. Accessed on May 2, 2007

15. Jemal A, Murray T, Ward E, Sammuels A et al. Cancer Statistics, 2007. Cancer Journal for Clinicians 2007; 57:43-66.

GlaxoSmithKline

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The number of lymph nodes that contain evidence of cancer is the best predictor of the effectiveness of adding chemotherapy and radiation to a treatment plan prior to surgery in individuals with oesophageal cancer, according to a study published last month in the Annals of Surgery. The authors say their finding is particularly important because the focus of recent pathological studies of response to neoadjuvant therapies has been on the primary tumour rather than nodal sites.

Multimodal neoadjuvant therapy—where suitable patients are given several cycles of drugs and radiation therapy before undergoing surgical procedures to remove their tumour—is increasingly being used by oncologists as a way to boost survival rates from oesophageal cancer which, even with the most radical surgery, remain low: only 50% of patients survive for 3 years. However, the evidence for which additional therapies work best is confusing and conflicting. What is more, although it is widely accepted that there is a group of patients in whom this approach works well, identifying who these patients are is no easy task.

To help find ways of pinpointing individuals who might respond best to neoadjuvant treatment, John Vincent Reynolds and colleagues followed the progress of 243 patients who were treated with chemotherapy and radiation before surgery over 5 years. They paid particular attention to the histomorphological responses of patients—changes in the structure and appearance of tissue samples when viewed under a microscope—in addition to assessing prognosis using the traditional TNM method of staging, which takes into account tumour size, involvement of lymph nodes (nodal status), and presence or absence of metastases.

The study group consisted of all patients undergoing neoadjuvant treatment for oesophageal cancer at St James’ Hospital in Dublin , Ireland . Patients with oesophageal cancer were deemed suitable for multimodal therapy if they fulfilled a list of pre-set criteria, including being younger than 77 years, fit for surgery, and having a tumour of resectable size and location. The patients were given a standard protocol of radiation therapy and concurrent chemotherapy with fluorouracil and cisplatin before undergoing thoracotomy with lympadenoctomy and nodal dissection; the extent of surgery and lymph node dissection depended on the exact location of the tumour. 30 patients did not proceed to surgery because of disease progression or deterioration in performance status.

Several tissue samples from each patient were extracted during surgery and were subsequently examined for extent of residual cancer, depth of invasion, and lymph node metastasis. The patients were also assigned a tumour stage according to the TNM staging system. All patients were followed up with 6 monthly endoscopy and annual CT scans.

Of the 213 patients who underwent surgery, 41 (19%) had a complete pathological response to the pre-surgery therapy, meaning there was no sign of cancer in the tissue samples. 31 (15%) of the remaining patients were classed as having stage 1 disease (the least advanced), 69 had stage 2 disease, and 72 (35%) had stage 3 disease. After a median follow up of 60 months, median survival for the whole group was 18 months. But for the group of patients who achieved a complete pathological response, 5-year survival was 50%, with median survival of 56 months. “The achievement of a complete pathologic response following neoadjuvant chemotherapy alone or in combination with radiotherapy for oesophageal tumours is a surrogate marker of survival advantage,” explain the authors.

However, the study established that it was nodal status rather than attainment of pathological response that was the most significant determinant of prognosis. When individuals with complete pathological responses were compared with those who had no nodal involvement after neoadjuvant therapy, there was no significant difference in the 1, 3, and 5 year survival rates. And within the node-negative group, the combination of complete response with a low tumour stage conferred better survival: individuals with stage 1 disease and no involved nodes (n=65) had a median survival of 67 months and 5-year survival of 53%, compared with 25 months and 30% for people with stage 2 and 3 tumours and no nodal involvement after neoadjuvant treatment. Interestingly, pretreatment clinical stage had no predictive value on histomorphological response.

The authors concluded that because the study suggests nodal status after neoadjuvant treatment is the strongest determinant of outcome, there is no evidence that an assessment of histomorphological response should be incorporated into a revised TNM system or that traditional methods of assessing prognosis should be altered. However, they added, histomorphological response might be a surrogate for nodal status and residual tumour volume therefore presenting the option of a non-operative approach in cases where the likelihood of nodal disease is small. According to the authors, the study also raises the question that if patients have no nodal involvement is neoadjuvant chemoradiotherapy justified at all?

“Long-term outcomes following neoadjuvant chemoradiotherapy for esophageal cancer”
John Vincent Reynolds, Cian Muldoon, Donal Hollywood, Narayanasamy Ravi, Suzanne Rowley, Ken O’Byrne, John Kennedy, Thomas J Murphy
Annals of Surgery 2007; 245:707-716

Cancer Research Summaries are overviews of important cancer research findings that have been reported in leading cancer publications. The Cancer Research Summaries are provided by the Cancer Media Service (CMS) in collaboration with Nature Clinical Practice Oncology.

CMS is a resource for journalists operated by the European School of Oncology (ESO). The CMS aims to improve the quality of cancer journalism by helping to put news about cancer in context and explaining the science behind the stories.

The CMS also offers workshops and briefing sessions for journalists interested in learning more about cancer. Don??t miss our media forum – Cancer: Time for a Reality Check and our award for promoting journalism: The Best Cancer Reporter Award.

All Cancer Research Summaries can be viewed at: cancerworld/mediaservice

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Vitamin E has been heralded for its ability to reduce the risk of blood clots, heart attack, and sudden death. Yet in some people, vitamin E causes bleeding. Scientists have known for more than 50 years that excess vitamin E promotes bleeding by interfering with vitamin K, which is essential in blood clotting. However, they haven’t been able to pinpoint how the two vitamins interact. Nutrition researcher Maret Traber of Oregon State University reviews studies of possible explanations of the interaction in an article published recently in Nutrition Reviews.

One of the most compelling studies of the benefits of vitamin E is the Women’s Health Study, in which 40,000 healthy women, 45 and older, took 600 IU vitamin E supplements or a placebo every other day for 10 years. Women taking the supplements had 24 percent fewer deaths from heart disease. Vitamin E’s protective effect appeared even stronger in women 65 and older. Those taking the vitamin experienced a 26 percent reduction in cardiovascular events and a 49 percent reduction in cardiovascular deaths.

“That’s a significant benefit,” Traber said. Yet, she added, “In some people high doses of vitamin E increase the tendency to bleed. Women enrolled in the study had an increase in nose bleeds.”

To lessen the bleeding risk, the U.S.-based Food and Nutrition Board in 2000 set the upper tolerable limit for daily vitamin E intake at 1500 I.U.

Research Traber reviewed suggests that a shared metabolic pathway in the liver causes vitamins E and K to interact. Vitamin K in the liver appears to diminish as vitamin E increases.

“Several different explanations could account for the interaction between the two vitamins,” Traber said. “We need more research to understand the delicate balance between vitamins E and K.”

This study is published in the November 2008 issue of Nutrition Reviews.

To view the abstract for this article, please click here.

Maret Traber is affiliated with Oregon State University .

Nutrition Reviews is a highly cited journal devoted to keeping academic researchers, students, and professionals abreast of the latest research in the field with authoritative and critical reviews of significant developments in all areas of nutrition science and policy.

Wiley-Blackwell was formed in February 2007 as a result of the acquisition of Blackwell Publishing Ltd. by John Wiley & Sons, Inc., and its merger with Wiley’s Scientific, Technical, and Medical business. Together, the companies have created a global publishing business with deep strength in every major academic and professional field. Wiley-Blackwell publishes approximately 1,400 scholarly peer-reviewed journals and an extensive collection of books with global appeal. For more information on Wiley-Blackwell, please visit wiley-blackwell or interscience.wiley.
Wiley-Blackwell was formed in February 2007 as a result of the acquisition of Blackwell Publishing Ltd. by John Wiley & Sons, Inc., and its merger with Wiley’s Scientific, Technical, and Medical business. Together, the companies have created a global publishing business with deep strength in every major academic and professional field. Wiley-Blackwell publishes approximately 1,400 scholarly peer-reviewed journals and an extensive collection of books with global appeal. For more information on Wiley-Blackwell, please visit blackwellpublishing/ or interscience.wiley/.

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Data published in the New England Journal of Medicine show that Erbitux® (cetuximab) significantly increases overall survival when added to standard chemotherapy in the 1st-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN).1 Results from the EXTREMEa trial also show that the addition of Erbitux to platinum-based chemotherapy significantly increases both median progression-free survival and tumor response rate, supporting the use of Erbitux in combination with chemotherapy as a new standard for 1st-line treatment of recurrent and/or metastatic SCCHN.1

“These findings are very exciting as they represent the first breakthrough in the treatment of head and neck cancer in this disease setting in 30 years,” commented Professor Jan B. Vermorken, lead investigator of the EXTREME trial and head of the Department of Medical Oncology, Antwerp University Hospital, Belgium. “The inclusion of Erbitux as part of the standard 1st-line treatment regimen for SCCHN will give patients valuable time with prolonged symptomatic relief from the effects of this aggressive form of cancer that is so difficult to treat.”

EXTREME was an open-label, multicenter, randomized, controlled Phase III trial that studied a total of 442 patients with previously untreated recurrent and/or metastatic SCCHN, who were randomized to receive Erbitux plus cisplatin or carboplatin and 5-fluorouracil (5-FU), or chemotherapy alone.1 The study found that the addition of Erbitux led to the following statistically significant outcomes:1

- Increased median overall survival of nearly 3 months (10.1 vs. 7.4 months; p=0.04), equating to a 20% risk reduction of death (HR: 0.80) during the study period
- A 70% increase in median progression-free survival (5.6 vs 3.3 months (p

Erbitux is already approved for use in locally advanced SCCHN in combination with radiotherapy and the results of the EXTREME trial have been used to support an EMEA application to broaden the use of Erbitux to include 1st-line treatment of recurrent and/or metastatic SCCHN, submitted in June 2008.

Head and neck cancer

In Europe alone, it is estimated that there are around 140,000 cases of head and neck cancer, and more than 65,000 deaths due to the disease each year.3 About 40% of patients with head and neck cancer have recurrent and/or metastatic SCCHN. Head and neck cancer is the sixth-most frequently occurring cancer worldwide3,4 and includes cancers of the tongue, mouth, salivary glands, pharynx, larynx, sinus and other sites located in the head and neck area. About 90% of head and neck cancers are of the squamous cell variety5 and nearly all express EGFR, which is critical for tumor growth.6 Although there have been significant improvements in chemotherapy and surgical techniques, the disease is particularly challenging to treat since most patients present with advanced disease and often have secondary tumors, in addition to suffering from other co-morbidities.7 At least 75% of all head and neck cancers are attributed to its two major risk factors, smoking tobacco and alcohol consumption.8

a EXTREME: ErbituX in 1st-line Treatment of REcurrent or MEtastatic head & neck cancer

References

1. Vermorken JB, et al. N Engl J Med 2008; 359:1116-27.
2. Herrero FR, et al. ESMO 2008; Abstract No: 693.
3. GLOBOCAN 2002 (www-dep.iarc.fr), accessed August 2008.
4. Vermorken JB, et al. J Clin Oncol 2007;25:(18S).
5. Hunter KD, et al. Nat Rev Cancer 2005;Feb;5(2):127-35.
6. Bourhis J & Pinto H. Redefining ‘State of the Art’ in Head and Neck Cancer. Oral presentation, 6th International Conference on Head and Neck Cancer 7-11 August 2004.
7. Forastiere A, et al. N Engl J Med 2001;345(26):1890-1900.
8. Hashibe M, et al. J Natl Inst 2007;99:777-89.

About Erbitux

Erbitux® is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.

The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.

Erbitux has already obtained market authorization in 75 countries. It has been approved for the treatment of colorectal cancer in 74 countries so far: Argentina, Australia, Belarus, Canada, Chile, China, Colombia, Costa Rica, Croatia, Dominican Republic, Ecuador, El Salvador, the European Union, Guatemala, Honduras, Hong Kong, Iceland, India, Indonesia, Israel, Japan, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, Moldavia, New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, South Korea, Switzerland, Taiwan, Thailand, Ukraine, Uruguay, the US, and Venezuela for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy. Erbitux is also approved for single-agent use in: Argentina, Australia, Canada, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Japan, Lebanon, Mexico, Moldavia, New Zealand, Nicaragua, Panama, Peru, the Philippines, Russia, Singapore, Thailand, the US, and Venezuela. In the European Union, the license was updated in July 2008 for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type mCRC (metastatic colorectal cancer) in combination with chemotherapy and as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan.

In addition, Erbitux in combination with radiotherapy has been approved for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in 68 countries: Argentina, Australia, Belarus, Brazil, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Indonesia, Israel, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, Moldavia, New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, South Korea, Switzerland, Taiwan, Ukraine, Uruguay, the US, and Venezuela. In Argentina, Chile, Costa Rica, El Salvador, Guatemala, Hong Kong, Israel, Lebanon, Mexico, Moldavia, Nicaragua, Peru, the Philippines, Russia, and the US, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.

Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems Incorporated of New York in 1998. In Japan, ImClone Systems Incorporated, Bristol-Myers Squibb Company and Merck jointly develop and, upon approval, commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck has also acquired the rights for the cancer treatment UFT® (tegafur-uracil) – an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.

Merck is also investigating among other cancer treatments the use of Stimuvax® (formerly referred to as BLP25 Liposome Vaccine) in the treatment of non-small cell lung cancer. The vaccine was granted fast-track status in September 2004 by the FDA. Merck obtained the exclusive worldwide licensing rights from Oncothyreon Inc., Bellevue, Washington, USA.

About Merck Serono

Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. Its North American business operates in the United States and Canada as EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux®), multiple sclerosis (Rebif®), infertility (Gonal-f®), endocrine and cardiometabolic disorders (Glucophage®, Concor®, Saizen®, Serostim®), as well as psoriasis (Raptiva®).

With an annual R&D investment of around ?‚¬ 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.

For more information, please visit merckserono or merck.de

About Merck

Merck is a global pharmaceutical and chemical company with total revenues of ?‚¬ 7.1 billion in 2007, a history that began in 1668, and a future shaped by 31,946 employees in 60 countries. Its success is characterized by innovations from entrepreneurial employees. Merck’s operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

Merck

View drug information on Erbitux; Gonal-F; Rebif. Continue reading →

Biothera announced today that it
has successfully completed a Phase I clinical trial for Imprime PGG(TM),
its investigational new drug for the treatment of various cancers and the
enhancement of white blood cell mobilization and production.

The single-dose, dose-escalating Phase I study examined the safety and tolerability of a single injection of Imprime PGG in 24 healthy volunteers.

As anticipated based on previous research, Imprime PGG demonstrated a strong safety profile.

“We are very pleased to have successfully completed our first trial in
humans,” said Myra Patchen, Ph.D., executive vice president of
pharmaceutical development for Biothera. “We are on track for moving
quickly to proof of concept Phase II trials.”

Biothera plans to initiate a multiple-dose, dose-escalation Phase I
clinical study in June. The study is designed to generate additional safety
data, including pharmacokinetic and pharmacodynamic data. Biothera is also preparing to launch a Phase II clinical program that will include a series of trials featuring a combination of Imprime PGG and various monoclonal antibodies and growth factors to treat a number of indications.

“Completion of the single-dose Phase I trial is a milestone for
Biothera and this platform technology,” said Daniel Conners, Biothera
founder and chairman. “Our strategy is to complete multiple Phase II trials
and then license these specific drug combinations to large biotech or
pharmaceutical companies.”

Imprime PGG is a soluble/injectable beta 1,3/1,6 glucan derived from a
proprietary strain of yeast (Saccharomyces cerevisiae). Imprime PGG binds with specific receptors on neutrophils, the most abundant immune cell in the body, and primes them for heightened immune activity. Preclinical studies demonstrate that Imprime PGG-bound neutrophils attack and kill cancer cells when complement and antibodies are present. In effect, this novel mechanism engages the innate immune system in the fight against cancer.

About Biothera, the Immune Health Company

Biothera is a biotechnology company dedicated to improving immune
health. The company’s primary focus is developing pharmaceuticals that
engage the immune system to fight cancer and that produce white blood cells following chemotherapy or radiation. In addition, Biothera manufactures and markets food-grade ingredients that support healthy immune function to the nutritional supplement, functional food, cosmetic and animal nutrition markets.

Biothera
biotherapharma Continue reading →

Landmark TARGET study shows up to 79% reduction of ulcer complications with Prexige versus established NSAIDs1

No increase in cardiovascular risk and more favorable blood pressure profile of Prexige versus NSAIDs2

Novartis Pharma AG announced today that results from a landmark trial showed that Prexige (lumiracoxib), the structurally distinct and most selective COX-2 inhibitor, demonstrated a significant 79% reduction in the incidence of upper gastrointestinal (GI) ulcer complications without compromising cardiovascular (CV) safety.

The results were the basis for two papers published online in The Lancet on the findings of the landmark TARGET (Therapeutic Arthritis Research & Gastrointestinal Event Trial of lumiracoxib) study that further confirmed the safety benefit of Prexige1,2.

“The excellent GI and CV safety profile of Prexige demonstrated by the positive results of TARGET shows a favorable benefit/risk ratio for Prexige, even at multiples of the normal chronic dose. These findings may be linked to the different chemical and pharmacokinetic properties of Prexige which is the most selective COX-2 inhibitor,” said Joerg Reinhardt, Head of Development, Novartis Pharma AG.

“With up to an estimated 16,500 GI-related deaths in the U.S. each year, these convincing data from 18,325 patients with osteoarthritis (OA) builds on the body of evidence suggesting that Prexige is effective while offering substantial GI safety benefits. TARGET fully supports the approved label in the UK and builds a strong basis for the ongoing European Mutual Recognition Process (MRP), which was recently started,” Reinhardt said.

TARGET is the largest GI safety outcomes study performed to date and clearly demonstrates beneficial results specifically for the GI safety of Prexige. The TARGET data demonstrate that in patients not taking low-dose aspirin, Prexige had an overall statistically significant reduction of 79% versus the two comparator NSAIDs (non-steroidal anti-inflammatory drugs) naproxen and ibuprofen in the incidence of definite or probable upper GI ulcer complications (p

In addition to GI tolerability, TARGET investigated CV safety. Prexige did not increase the CV risk (defined as the combined Anti-Platelet Trialist Collaboration [APTC] endpoint) compared to the two NSAIDs. The APTC endpoint included confirmed or probable non-fatal myocardial infarction (MI) including silent MI (ECG-detected), non-fatal stroke (ischemic or hemorrhagic) and cardiovascular death.

For the APTC endpoint, no significant difference between Prexige and the comparator NSAIDs was observed in the overall population, or in the populations investigated separately for those taking or not taking low-dose aspirin.

Furthermore, there was no significant difference in the incidence of MIs, congestive heart failure and other thrombotic events observed in the overall population groups studied between Prexige and naproxen or ibuprofen2.

“TARGET demonstrates that Prexige has a CV profile similar to conventional NSAIDs with a more favorable blood pressure profile. These very important results show that Prexige offers GI benefits to patients without compromising their CV safety,” said Dr. Michael Farkouh, Director of the Cardiac Care Unit at New York University Medical Center and Chair of the TARGET Cardio-Cerebrovascular adjudication committee. “In TARGET, we found no difference in MIs, stroke or any of the other CV endpoints investigated between Prexige and ibuprofen or naproxen.”

For the pre-specified endpoint combining serious GI and CV events, Prexige at up to four times the recommended dose for OA showed a significant 35% reduction (p=0.001) versus the NSAID groups1. Importantly, mean changes in systolic and diastolic blood pressure from baseline for patients taking Prexige were significantly smaller (p?‰¤0.0001) than for those taking NSAIDs (systolic +0.4 mmHg vs. +2.1 mmHg respectively; diastolic -0.1 mmHg vs. +0.5 mmHg respectively)1,2.

Serious GI or CV events are more frequent side effects in patients treated with NSAIDs and
COX-2 selective inhibitors than serious hepatic events, as confirmed in TARGET with a more than ten times higher frequency of serious GI and CV events than hepatic events. In TARGET, there was no significant difference in serious hepatic events leading to jaundice between Prexige and the NSAID groups1. Of the approximately 9,000 patients using twice the maximum dose of Prexige for use in OA, six cases of jaundice were observed [0.07%], while two cases in the group using ibuprofen [0.05%] and one with naproxen [0.02%] at therapeutic doses with approximately 4,500 patients in each group. After discontinuation of therapy, all effects resolved fully. Less serious and transient hepatic enzyme elevations were recorded more often with Prexige compared to NSAIDs [2.6% versus 0.6% respectively], but were less frequent than seen with the most widely prescribed NSAID diclofenac [4%]8.

Recently completed studies with Prexige 100 mg daily in OA have shown hepatic enzyme elevations to be comparable to placebo at 13 weeks [0.25% 3xULN] (data on file).

About TARGET

TARGET was designed to answer questions about the overall safety of Prexige, building on the experience and shortcomings of previous GI outcomes trials of celecoxib (CLASS study) and rofecoxib (VIGOR study)3. In total, 18,325 patients participated in TARGET, randomized at more than 800 trial sites worldwide. The trial was designed to examine GI safety as the primary endpoint and CV safety as a secondary endpoint of Prexige 400 mg once daily – two or four times the indicated dose for use in OA – versus standard doses of ibuprofen 800 mg three times daily and naproxen 500 mg twice daily over 12 months. TARGET is also the first outcomes study designed to examine the impact of low-dose aspirin with Prexige on both GI and CV safety. In keeping with a “real-life” OA population, 24% of the randomized patients in TARGET included low-dose aspirin with their study medication for primary and secondary prevention of CV disease3.

TARGET had several key differentiating features. The large size of the trial (>18,000 patients), a high retention rate at one year (60%), the choice of homogenous study population with OA and stratifying at randomization 24% of the patient population for low dose aspirin use (75-100 mg daily) all contributed to providing the power necessary to investigate the serious GI events that can occur with regular NSAID use in a representative OA population. The study design also permitted an assessment of the influence of low-dose aspirin on the GI benefit, a comparison with two NSAIDs with different anti-thrombotic properties, and a prospective investigation of key cardiovascular endpoints in patients taking, or not taking, concomitant low-dose aspirin. The TARGET study began in late 2001 and enrolled patients in the US, Europe, South America, Canada, South Africa and Asia. The TARGET protocol was reviewed by the US Food and Drug Administration (FDA), and study data were evaluated on an interim basis by an independent data and safety monitoring board.

About Prexige

Prexige was developed for the treatment of the signs and symptoms of arthritis and management of pain. Prexige is the most selective cyclooxygenase-2 (COX-2) inhibitor with a non-sulfur containing structure distinct from existing selective COX-2 inhibitors4. Prexige has proven efficacy in an extensive phase III clinical trial program demonstrating rapid onset in acute pain with 400mg once daily (od) for short term use5 and efficacy in OA with 100mg od (data on file) and 200mg od6 and rheumatoid arthritis at 200mg od7.

Novartis has filed applications for regulatory approval throughout the world based on data from more than 40 pre-clinical and clinical studies in OA, rheumatoid arthritis, acute pain and primary dysmenorrhea involving more than 13,000 adult patients around the world. Prexige has been approved in 17 countries to date, including the United Kingdom, Australia and several countries in Latin America, including Argentina, Brazil and Mexico. Novartis have shared the TARGET data with all health authorities, including the UK Health Authority and the MHRA, and are currently initiating the Mutual Recognition Procedure (MRP) process in Europe.

About Osteoarthritis

Osteoarthritis (OA), the most common form of arthritis, is characterized by the breakdown of cartilage in joints, causing affected bones to rub against each other. This often leads to inflammation, pain and loss of movement. Globally, OA accounts for half of all chronic conditions in people age 65 and older, with an estimated 103 million Europeans and 20.7 million Americans affected. The economic impact of musculoskeletal diseases, including OA, is substantial, costing the US nearly $65 billion annually in direct expenses, lost wages and production. Risk factors associated with OA include accidents, age, joint injuries due to sports, obesity or work-related activity.

About Novartis

Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2003, the Group’s businesses achieved sales of USD 24.9 billion and a net income of USD 5.0 billion. The Group invested approximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 80,000 people and operate in over 140 countries around the world. For further information please consult novartis.

Disclaimer

The foregoing press release contains forward-looking statements that can be identified by terminology such as “may be”, “suggesting”, “builds a basis” or similar expressions, or by express or implied discussions regarding potential future regulatory filings, approvals or future sales of Prexige (lumiracoxib). Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that any future regulatory filings will satisfy the FDA’s and other health authorities’ requirements regarding Prexige, that Prexige will be approved by the FDA or by any other country’s health authorities for any indication, or that Prexige will reach any particular level of sales. In particular, management’s expectations regarding Prexige could be affected by, among other things, uncertainties relating to clinical trials and product development, including additional clinical trials which must be conducted in the future in order to satisfy FDA’s requirements; regulatory actions or delays or government regulation generally; the ability to obtain or maintain patent or other proprietary intellectual property protection; government, industry, and general public pricing pressures; and competition in general; as well as factors discussed in the Company’s Form 20F filed with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Novartis is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

References

1. Schnitzer TJ, Burmester G R, Mysler E, Hochberg MC, Doherty M, Ehrsam E, Gitton X, Krammer G, Mellein B, Matchaba P, Gimona A, Hawkey CJ, on behalf of the TARGET Study Group. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: a randomised controlled trial. Lancet 2004; 364(9435):665-674

2. Farkouh ME, Kirshner H, Harrington RA, Ruland S, Verheugt FWA, Schnitzer TJ, Burmester G R, Mysler E, Hochberg MC, Doherty M, Ehrsam E, Gitton X, Krammer G, Mellein B, Gimona A, Matchaba P, Chesebro JH on behalf of the TARGET Study Group. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: a randomised controlled trial. Lancet 2004; 364(9435):675-684

3. Hawkey CJ, Farkouh M, Gitton X, Ehrsam E, Huels J, Richardson P. Therapeutic Arthritis Research and Gastrointestinal Event Trial of lumiracoxib – study design and patient demographics. Aliment Pharmacol Ther 2004;20(1):51-63.

4. Brune K, Hinz B. Selective cyclooxygenase-2 inhibitors: similarities and differences. Scand. J. Rheumatol. 2004;33:1-6

5. Kellstein D, Ott D, Jayawardene S, Fricke J Jr. Analgesic efficacy of a single dose of lumiracoxib compared with rofecoxib, celecoxib and placebo in the treatment of postoperative dental pain. Int J Clin Pract 2004;58(3):244-250.

6. Tannenbaum H, Berenbaum F, Reginster J-Y, Zacher J, Robinson J, Poor G, Bliddal H, Uebelhart D, Adami S, Navarro F, Lee A, Moore A, Gimona A. Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a 13-week, randomized, double-blind study versus placebo and celecoxib. Ann Rheum Dis Published Online First February 27 2004. doi: 10.1136/ard.2003.015974.

7. Geusens P, Alten R, Rovensky J, Sloan V, Krammer G, Kralidis G, Richardson P. Efficacy, safety and tolerability of lumiracoxib in patients with rheumatoid arthritis: Results of a randomized double-blind study. Arthritis Rheum 2003;48(Suppl. 9):242 (Abstract 544).

8. Diclofenac US package insert Continue reading →

The Crohn’s Disease Activity Index (CDAI), which relies on patient symptoms to determine whether or not Crohn’s disease is active, may not reliably indicate whether a patient’s disease has returned after corrective surgery, according to a study published in this month’s issue of Inflammatory Bowel Diseases.

According to Miguel Regueiro, M.D., associate professor of medicine and co-director of the Inflammatory Bowel Disease Center at the University of Pittsburgh School of Medicine, the CDAI relies on patients reporting their symptoms to determine whether or not Crohn’s disease has recurred or gone into remission after surgery.
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“The natural course of Crohn’s disease often is symptom-free,” explained Dr. Regueiro. “The disease can present silently. In fact, many patients with Crohn’s may have had disease for years without having symptoms. Similarly, after surgery, most patients feel quite well for many years. We have found that most patients with recurrent Crohn’s disease after surgery also do not have symptoms. This is a concern because many patients with post-surgical Crohn’s disease recurrence will ultimately need another surgery and if they cannot feel their disease, adequate treatment may not be started. Because of this, we need to look for objective evidence of the disease instead of relying on patients to report how they feel.” ? 
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The study sought to discover whether disease recurrence detected by endoscopy agreed with patient symptom reports. Twenty-four patients with Crohn’s disease were randomly assigned to a post-operative clinical trial that assessed disease recurrence. According to the results, half of the patients went into remission after surgery while the other half did not, and there was little or no relationship between the return of the disease and the symptoms patients reported.
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“Because patient symptoms don’t indicate whether Crohn’s disease has returned, we need to change how we consider symptom-based care and begin utilizing objective evidence, such as endoscopy, to understand the course the disease takes in individual patients. This way, we can detect the disease early, begin the correct treatment, and potentially prevent future complications and the need for more surgery,” said Dr. Regueiro.
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Crohn’s disease is a form of inflammatory bowel disease that usually affects the intestines. Symptoms can range from mild to severe, and include crampy abdominal pain, fatigue, unexplained weight loss, diarrhea, liver inflammation and skin rash. Without proper treatment, Crohn’s can lead to bowel complications such as obstructions and infection, as well as problems outside of the intestines, like inflammation of the joints and vitamin deficiencies.
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Continue reading →

Nabi
Biopharmaceuticals (Nasdaq: NABI) today announced that it has secured an
agreement with Kedrion S.p.A., a global biopharmaceutical company, located
in Lucca, Italy. Under the terms of the agreement, Nabi Biopharmaceuticals
and Kedrion will pursue a common strategy to develop and commercialize
Civacir(R) [Hepatitis C Immune Globulin (Human)] in Europe and the U.S.,
with Kedrion being Nabi Biopharmaceuticals’ exclusive licensee to
commercialize Civacir in Europe. Civacir is Nabi Biopharmaceuticals’
plasma-derived, polyclonal antibody product candidate, which, when
approved, would be the first therapy for the prevention of the recurrence
of hepatitis C-related liver disease in HCV-positive liver transplant
recipients, or in patients who receive an HCV- positive liver. In addition
to milestone and royalty payments to be paid to Nabi Biopharmaceuticals,
Kedrion will assume development costs for the product candidate in both
Europe and the U.S. through at least Phase II clinical trials.

“This agreement represents a major funding event for Nabi
Biopharmaceuticals. It is also a validation of the clinical and commercial
potential of the Civacir program. This agreement marks a successful
achievement of a stated company objective to form strategic partnerships to
advance our pipeline programs,” stated Thomas H. McLain, chairman, chief
executive officer and president, Nabi Biopharmaceuticals. “Kedrion is the
recognized leader in plasma-derived products in Italy and is helping to
drive the evolution of the broader marketplace within Europe for these
products. Kedrion’s leadership role in this transformation provides us with
a rare and exciting opportunity to speed the clinical and commercial
advancement of Civacir across Europe and does so in a way that is
financially advantageous to Nabi Biopharmaceuticals. We are thrilled to
begin this partnership with Kedrion and believe that it may afford us the
chance to explore other, mutually beneficial collaborations between our two
companies.”

Mr. McLain continued, “This agreement is aligned with our 2006 to 2008
growth strategy, focused on optimizing the value of current operations,
building incremental value through strategic partnerships and commercial
alliances, and demonstrating proof-of-concept through clinical studies for
key programs in our pipeline. We look forward to readily advancing this
program in collaboration with Kedrion.”

Paolo Marcucci, President and Managing Director, Kedrion S.p.A.,
stated, “While the number of vulnerable patients continues to rise, there
remains no commercially available products that can be dosed safely at the
time of transplant or immediately after transplant in hepatitis C-positive
liver transplant recipients. We believe that Civacir, if approved, would
fill a critical and growing void in viable treatment options for
HCV-positive liver transplant recipients and patients who receive an
HCV-positive liver.

We are looking forward to developing this clinically and commercially
important product with Nabi Biopharmaceuticals.”

Gary L. Davis, M.D., Director, Division of Hepatology, Medical
Director, Liver Transplantation, Baylor Regional Transplant Institute,
Baylor University Medical Center, stated, “There is an unmistakable need
for a new approach to preventing the recurrence of hepatitis C-related
liver disease in HCV-positive liver transplant recipients. It is well
established that currently approved therapies have minimal efficacy in
treating this population and that the inevitable re-infection of the liver
leads to an increase in a number of serious health risks, most concerning
of which is loss of the transplanted organ. The polyclonal antibody
approach of Civacir, either alone or in combination with new antiviral
agents that may be developed in the future, is a potential way to
neutralize the numerous strains of hepatitis C virus that exist and the
dire health consequences that they cause.”

Next Steps: Civacir Development Program

Under the terms of the agreement announced today, Nabi
Biopharmaceuticals and Kedrion will jointly oversee the development and
registration of Civacir in Europe and will work collaboratively on the
design and implementation of the Phase II clinical trial for Civacir, which
will be conducted in Europe and the U.S. The trial is planned to be
initiated in the second half of 2006.

With positive results from the Phase II trial, the two companies would
then collaborate on the development of a pivotal Phase III trial for
Civacir. The pivotal study would also be conducted in the U.S. and Europe.
It is expected that the results of this trial, if positive, would be
sufficient to obtain the regulatory approvals needed for Kedrion to market
Civacir in Europe and for Nabi Biopharmaceuticals to obtain regulatory
approval to market the product in the United States.

About Civacir

Civacir is an investigational human polyclonal antibody product that
contains antibodies to the hepatitis C virus (HCV). In February 2006, Nabi
Biopharmaceuticals announced that Civacir had been granted Fast Track
Designation by the U.S. Food and Drug Administration (FDA). This
designation facilitates the development of products that treat serious
diseases where an unmet medical need exists. Civacir has also gained Orphan
Medicinal Product (OMP) designation in Europe. If a product with OMP
designation is the first to receive marketing authorization in Europe for
its designated indication, the product will be entitled to 10-year market
exclusivity, thereby preventing a similar drug from receiving authorization
for the same indication during this period. Civacir also has Orphan Drug
Status in the United States. This provides a seven-year period of market
exclusivity in the United States when the product is approved.

About Nabi Biopharmaceuticals

Nabi Biopharmaceuticals leverages its experience and knowledge in
powering the immune system to develop and market products that fight
serious medical conditions. The company has three products on the market
today: PhosLo(R) (calcium acetate), Nabi-HB(R) [Hepatitis B Immune Globulin
(Human)], and Aloprim(TM) (allopurinol sodium) for Injection. Nabi
Biopharmaceuticals is focused on developing products that address unmet
medical needs and offer commercial opportunities in our core business
areas: Gram-positive bacterial infections, hepatitis and transplant, kidney
disease (nephrology) and nicotine addiction. For a complete list of
pipeline products, please go to: nabi/pipeline/index.php.
The company is headquartered in Boca Raton, Florida. For additional
information about Nabi Biopharmaceuticals, please visit our Website at:
nabi.

About Kedrion S.p.A.

Kedrion is a biotechnology company specializing in the development,
production and distribution of plasmaderivatives. In Italy, Kedrion is the
main reference point for the National Health Service as regards the
production of plasma-derived drugs. Moreover, its skills are also put to
use in strategic partnerships with overseas health services. The quality of
its products, its continuous commitment to research and development, its
consistent industrial capacity and its consolidated presence on the
national and international market are the company’s main areas of
competitiveness. Kedrion SpA is the parent company of a group comprising:
Hardis SpA, Haemopharm, Advanced Bioservices LLC. It is located in
Castelvecchio Pascoli, in the province of Lucca, Tuscany, and has two
production plants, Kedrion Bolognana, in the vicinity of Lucca and Hardis
S. Antimo, in the vicinity of Naples. Kedrion is characterized by its focus
on the international scene and its commitment to improving its local
plants. The specific assets of the various companies allow Kedrion to offer
partner companies and health institutes a complete and integrated approach
within the field of plasmaderivatives. Thanks to these assets, Kedrion is
able to manage the entire plasma processing cycle, from its acquisition to
the distribution of plasma-derived products, including logistical support
services. Kedrion’s operations cover three different areas of business:
production and distribution of plasma-derived products (it produces
plasma-derived drugs and virus deactivated plasma and it also distributes
flu vaccines), Contract Manufacturing (working with the National Health
Service, Kedrion receives the plasma from the regions and transforms it
into drugs that are redistributed to the regions in order to respond to the
population’s therapeutic requirements), transfer of technological know how
(by means of international partnerships, it offers its technological know
how concerning two main activities, the construction of plasma-derived
product production plants and the transfer of technological production
processes). Its Website is kedrion.

Forward-Looking Statement

Statements in this press release about the company that are not
strictly historical are forward-looking statements and include statements
about our products in development, the market for such products, and
regulatory approval of our product candidates. You can identify these
forward-looking statements because they involve our expectations, beliefs,
intentions, plans, projections, or other characterizations of future events
or circumstances. These forward-looking statements are not guarantees of
future performance and are subject to risks and uncertainties that may
cause actual results to differ materially from those in the forward-looking
statements as a result of any number of factors. These factors include, but
are not limited to, risks relating to the company’s ability to advance the
development of products currently in the pipeline or in clinical trials;
maintain the human and financial resources to commercialize current
products and bring to market products in development; obtain regulatory
approval for its products in the U.S., Europe or other markets;
successfully develop, manufacture and market its products; successfully
partner with other companies; realize future sales growth for its
biopharmaceutical products; maintain sufficient intellectual property
protection or positions; raise additional capital on acceptable terms;
re-pay its outstanding convertible senior notes when due. Many of these
factors are more fully discussed, as are other factors, in the company’s
Annual Report on Form 10-K for the fiscal year ended December 31, 2005 and
Quarterly Report on Form 10-Q for the Quarter ended April 1, 2006 filed
with the Securities and Exchange Commission.

Nabi Biopharmaceuticals
nabi Continue reading →