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Brain Cancer News for June 2004

Risky Procedure Saves A Life

June 29 — Each year, more than 15,000 people will find out they have a brain tumor. With the most deadly form, few survive two years. Dr. Dean Edell reports on one woman who is beating the odds.

Maria Elena Hartmann: "My son, right now, he's in Iraq. This is my favorite picture, right here. He's making history right here." Maria is also making history. She had surgery to remove a grade-four malignant brain tumor -- the deadliest type of brain cancer. That was seven years ago.

Maria Elena Hartmann, brain cancer patient: "I went to surgery with make-up and with my nails done and everything. I wasn't going there to die. I trusted them completely. They are completely heroes to me." She means that literally. The heroes – Dr. Roberto Heros, a neurosurgeon, and his wife Deborah, a neuro-oncologist. Their last name makes patients think they have a superhero on their side.

Dr. Deborah Heros, neuro-oncologist: "When some patients do make that joke, I kind of have to step back and think, 'Oh, if only we could do more.'" For Maria, they did do more. After Dr. Heros removed Maria's tumor, he implanted chemotherapy wafers into the cavity. He took a risk that day. The wafers were only approved for cancer recurrences - not as first-line treatment.

Dr. Roberto Heros, neurosurgeon: "We're here to do what we think is best for the patient and the rest of the considerations are really trivial if you're thinking about being afraid that we're going to get sued." Maria says they told her about the risks involved, but it was an easy decision to make. Maria: "My son, he always tells me, 'Mom, you're my hero.' I tell him that he's my hero."

Maria continues to beat the odds, and she says she's not going anywhere until her son comes home. Recently the chemo wafers were approved for use as a first-line treatment, yet surgeons have been slow to start using them because their success-rate is still unproven. But many patients think it's worth the risk.

Peregrine Pharmaceuticals Announces Patent Grants for Vascular Targeting Agents

TUSTIN, Calif., June 28 /PRNewswire-FirstCall/ -- Peregrine
Pharmaceuticals, Inc. (Nasdaq: PPHM) announced today the grant of European Patent No. EP 0988056 B1, entitled "Tissue Factor Methods and Compositions for Coagulation and Tumor Treatment" and the issuance of U.S. Patent No. 6,749,853, entitled "Combined Methods and Compositions for Coagulation and Tumor Treatment." Both patents cover agents that occlude (coagulate) tumor blood vessels for therapeutic applications. The U.S. patent is part of Peregrine's Vascular Targeting Agent (VTA) technology platform. Peregrine's VTAs specifically bind to tumor blood vessels and shut down blood flow to the tumor resulting in tumor cell death. Peregrine is currently evaluating the use of VTAs incorporating Tissue Factor for the treatment of cancer.

"The issuance of the European patent is a particularly important extension of coverage for Tissue Factor based therapeutics since Europe represents a major worldwide market for cancer therapeutics," said Steven King, president and CEO of Peregrine. "We believe there will be a number of licensing and co-development opportunities for compounds that may fall under our patent portfolio, so any extension of our already broad coverage is beneficial." Peregrine's VTA patent estate includes more than 190 issued or pending U.S. and foreign patents and patent applications.

About Vascular Targeting Agents
VTAs developed by Dr. Thorpe and his team represent the next generation of cancer therapy that works by a novel mechanism of action. Essentially, all detectable tumors rely on blood vessels to obtain oxygen and nutrients. Peregrine's VTAs localize within the tumor vasculature by selectively binding to the flat endothelial cells that line tumor blood vessels. Once the VTA binds to its target, it occludes the tumor vessels. Because blockage of a single capillary results in the destruction of thousands of tumor cells, only a small quantity of VTAs localized in the tumor's vascular system may cause an avalanche of tumor cell death.

There are thought to be a number of advantages of VTAs over other cancer therapies making them potentially powerful anti-cancer treatments. By targeting receptors unique to tumor cell vasculature, VTAs can kill tumors by cutting off oxygen and nutrients without causing damage to surrounding healthy tissue. VTAs produce a characteristic pattern of necrosis after administration to mice and rats with solid tumors. They cause a widespread central necrosis that can extend to as much as 95% of the tumor. Additionally, VTAs reduce the
risk of potential side effects by operating at lower dosages than raditional cancer therapies because they do not need to penetrate the innermost part of a tumor to take effect. Lastly, while drug resistance caused by the instability and mutability of cancer cells is a significant problem with conventional therapies that target tumor cells, the cells targeted by VTAs do not mutate to become drug resistant. Peregrine believes that VTAs will be most effective when used in combination with existing anti-cancer therapies, providing a powerful "1-2 punch" for the effective treatment of various solid tumor cancers.

About Peregrine Pharmaceuticals, Inc.
Peregrine's research and development efforts focus on discovering and
developing products that affect blood flow to tumors. Peregrine's vascular research programs fall under several different proprietary platforms including Anti-Phospholipid Therapy (APT), Vascular Targeting Agents (VTAs), Anti-Angiogenesis and Vasopermeation Enhancement Agents (VEAs). The company has research collaborations with pharmaceutical and biotechnology companies to develop its VTA platform for therapeutic and diagnostic applications and expects to enter its first APT compound into clinical trials for cancer therapy during calendar year 2004.

Peregrine's vascular agents may also have applications in other
angiogenesis-dependent diseases besides cancer such as diabetes, arthritis, skin disorders and eye diseases. Peregrine currently has exclusive rights to over 190 U.S. and foreign patents and patent applications that broadly cover its vascular programs. In addition, the company is currently evaluating its proprietary technology for use in treating non-angiogenesis dependent diseases such as viral infections. The company believes that the pre-clinical data generated by the company and the broad nature of its intellectual property may provide many opportunities for product development, partnering and licensing.
Peregrine's most clinically advanced therapeutic program is based on a
targeting platform outside vascular biology. This technology platform is known as Tumor Necrosis Therapy (TNT) and targets dead or dying tumor cells that are common to the majority of different tumor types. Cotara(TM), the most clinically advanced TNT program, is currently in a Phase I clinical trial for the treatment of colorectal carcinoma at Stanford University Medical Center.

In addition, we have received protocol approval from the U.S. Food and Drug Administration ("FDA") to initiate a registration clinical study for the treatment of brain cancer. The company is currently seeking a development or funding partner to move the brain cancer program forward. The company believes that continuing the clinical development of Cotara(TM) in tumor types other than brain cancer will add significant value to the program. The company has a research collaboration to develop immunocytokines based on the TNT platform and a TNT based agent has been developed and approved for the treatment of
lung cancer in China under a licensing agreement.

Los Angeles, CA, Jun. 22 (UPI) -- Laminin-8 genes and their resulting protein may be effective targets in fighting malignant brain tumors, an international research team has found.

Researchers led by the Cedars-Sinai Maxine Dunitz Neurosurgical Institute found over-expression of laminin-8 can predict a tumor's grade, recurrence and the patient's survival chances.

The thin membrane under the surface of blood vessels contains proteins called laminins. Researchers found during tumor progression, laminin-9, which is weakly expressed in normal brain tissue and low-grade tumors, switched to laminin-8, whose expression increased significantly with progression.

Researchers analyzed normal brain tissue and brain tumor tissue and found higher laminin-8 levels in more advanced tumors, which related to faster tumor recurrence after tumor-removal surgery and shorter patient survival times.

Affitech AS and Peregrine Pharmaceuticals Announce Research Milestone Achievement by Affitech

TUSTIN, Calif., and OSLO, Norway, June 24 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM - News) and Affitech AS today announced that they have achieved the first research milestone in one of their research collaborations. The milestone involved the identification of an initial panel of fully human antibodies that bind to the blood vessel growth factor Vascular Endothelial Growth Factor (VEGF) with a defined specificity. As part of the collaboration, Affitech will further optimize the panel of antibodies using its proprietary discovery and selection systems. The antibodies are intended to be used in Peregrine's Vascular Targeting Agent (VTA) and anti-angiogenesis programs.

"With this significant accomplishment, Affitech has demonstrated to be a reliable partner for antibody discovery and development," commented Martin Welschof, Ph.D., Chief Executive Officer of Affitech. "The quality of our human antibody libraries in combination with a tailor-made screening process was instrumental in achieving this milestone. We are delighted to have reached this important milestone in building a human antibody-based product portfolio for Peregrine."

Commenting on the collaboration, Steven King, Peregrine's president and CEO said, "Our mutual goal as we entered into the collaboration with Affitech was to identify a number of fully human monoclonal antibodies that could be used for our VTA and anti-angiogenesis technology platforms. We have been working very closely with Affitech on the anti-VEGF program and are pleased to have met an important milestone that brings us one step closer to identifying new clinical candidates for our anti-angiogenesis and VTA programs. We look forward to continuing a successful collaboration with Affitech as we expand our clinical pipeline."

About Affitech AS

Affitech AS is a human antibody therapeutics company based in Oslo, Norway, having its U.S. subsidiary in the San Francisco Bay Area. The Company's primary focus is in the discovery and development of human therapeutic antibodies for cancer, infectious and other diseases of unmet medical needs. Affitech's technology portfolio includes its worldwide patents of a phagemid system for antibody and antibody fragments, as well as its proprietary AffiScreeN(TM) method that utilizes patient-derived antibody repertoires in a high-throughput screening platform. More significantly, Affitech's recent implementation of the C.B.A.S. system, which is an integrated functional cell-based screening approach for simultaneous discovery of human antibodies and cognate targets, further emphasizes its ongoing focused efforts in "advancing antibody therapeutics." Affitech's business strategy is to generate short-term revenue through customer-based projects and out-licensing of technology assets and early stage products, and in addition to build a proprietary product pipeline through collaborations and partnerships. Affitech has concluded deals with NatImmune, Peregrine and Viventia. Most recently Affitech and the Norwegian Radium Hospital were awarded NOK 6.2 million from FUGE (the Norwegian national FUnctional GEnomics program) to carry out research on the development of new cancer therapeutics, vaccines and diagnostics. Further information can be found at http://www.affitech.com.

About Peregrine Pharmaceuticals, Inc.

Peregrine's research and development efforts focus on discovering and developing products that affect blood flow to tumors. Peregrine's vascular research programs fall under several different proprietary platforms including Anti-Phospholipid Therapy (APT), Vascular Targeting Agents (VTAs), Anti- Angiogenesis and Vasopermeation Enhancement Agents (VEAs). The company has research collaborations with pharmaceutical and biotechnology companies to develop its VTA platform for therapeutic and diagnostic applications and expects to enter its first APT compound into clinical trials for cancer therapy during calendar year 2004.

Peregrine's vascular agents may also have applications in other angiogenesis-dependent diseases besides cancer such as diabetes, arthritis, skin disorders and eye diseases. Peregrine currently has exclusive rights to over 190 U.S. and foreign patents and patent applications that broadly cover its vascular programs. In addition, the company is currently evaluating its proprietary technology for use in treating non-angiogenesis dependent diseases such as viral infections. The company believes that the pre-clinical data generated by the company and the broad nature of its intellectual property may provide many opportunities for product development, partnering and licensing.

Peregrine's most clinically advanced therapeutic program is based on a targeting platform outside vascular biology. This technology platform is known as Tumor Necrosis Therapy (TNT) and targets dead or dying tumor cells that are common to the majority of different tumor types. Cotara(TM), the most clinically advanced TNT program, is currently in a Phase I clinical trial for the treatment of colorectal carcinoma at Stanford University Medical Center. In addition, we have received protocol approval from the U.S. Food and Drug Administration ("FDA") to initiate a registration clinical study for the treatment of brain cancer. The company is currently seeking a development or funding partner to move the brain cancer program forward. The company believes that continuing the clinical development of Cotara(TM) in tumor types other than brain cancer will add significant value to the program. The company has a research collaboration to develop immunocytokines based on the TNT platform and a TNT-based agent has been developed and approved for the treatment of lung cancer in China under a licensing agreement.

The company also operates a cGMP contract manufacturing facility for monoclonal antibodies and recombinant proteins through its wholly owned subsidiary Avid Bioservices, Inc. (http://www.avidbio.com). Avid produces clinical trial materials to support Phase I through Phase III clinical trials for biotechnology companies including Peregrine. Copies of Peregrine press releases, SEC filings, current price quotes and other valuable information for investors may be found on the website http://www.peregrineinc.com.

Medicare to Extend Access to Certain Drugs for Beneficiaries with Serious and Chronic Illnesses

FOR IMMEDIATE RELEASE Thursday, June 24, 2004
HHS Secretary Tommy G. Thompson today announced a new Medicare demonstration program that will save seniors and persons with disabilities substantial money -- up to 90 percent in some cases -- on the life-enhancing medicines they take for serious diseases, including cancer, multiple sclerosis and rheumatoid arthritis.

The demonstration program, created as part of the Medicare Modernization Act, will extend Medicare coverage to prescription medicines that can be self-administered rather than administered by a health care provider. The demonstration will help up to 50,000 beneficiaries with serious illnesses who do not have comprehensive prescription drug coverage today.

"This demonstration will provide access and affordability to life-saving medicines for people fighting serious diseases," Secretary Thompson said.  "Through this coverage, seniors will save thousands of dollars on essential medicines that they can take at home. It will relieve some of the burden of battling a debilitating disease."

The initiative, known as the Medicare Replacement Drug Demonstration, was mandated under Section 641 of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA). As set by Congress, enrollment in the demonstration will be open to 50,000 people and total spending on the covered drugs will be up to $500 million.

Under this initiative, Medicare will pay for certain drugs and biologicals that can be taken by the patient at home and that replace drugs which are currently covered under Medicare Part B when given in a doctor’s office.  In addition, newer, more effective medications that replace some currently covered oral anti-cancer drugs will also be covered.

"Covering drugs that you can administer yourself improves access to high-quality care", said Mark B. McClellan, M.D., Ph.D., administrator of the Centers for Medicare & Medicaid Services (CMS). "In some cases, by avoiding the need for doctor visits and intravenous injections, costs and medical complications may be reduced and access and ease of treatment will increase. And many beneficiaries will get literally tens of thousands of dollars worth of help in purchasing these critical medicines right away, ahead of the Medicare drug benefit in 2006."

Drugs for treatment of such diseases as rheumatoid arthritis, multiple sclerosis, pulmonary hypertension and a variety of cancers will be included in the demonstration. The drugs were selected based on criteria developed after extensive input from physicians and other experts.  The drugs and the diseases that are covered are listed below.

Beneficiary cost sharing for these drugs will mirror the "standard" Medicare Part D prescription drug benefit when it is implemented in 2006 (participants will not pay the monthly premium in the demonstration, however).  Beneficiaries with limited resources and incomes of less than 150 percent of the federal poverty level (FPL) will have even lower cost sharing requirements.

The demonstration will give Medicare beneficiaries a glimpse of the significant savings coming their way when the Part D prescription drug benefit is fully implemented in 2006.

Examples of estimated savings over a year include:

• Patients with Chronic Myelogenous Lymphoma (a cancer) using Gleevec could save nearly 90 percent or $40,654 annually. Gleevec has an estimated annual cost of $45,952, but patients in the demo would o

nly pay $5,298.

• Patients with Multiple sclerosis could save 75 percent or $12,260 annually off medicines that cost an estimated $16,298 annually. They would pay only $4,038.

• Patients with rheumatoid arthritis could save 75 percent or $11,975 annually off medicines that cost an estimated $16,000. They would pay only $4,025.

• And patients with pulmonary hypertension using Tracleer could save 86 percent or $31,255 off of a cost that otherwise could reach $36,136. They would pay only $4,881.

Low–income beneficiaries in the demonstration would save significantly more.  Using the above examples, for those between 135 and 150 percent of the FPL estimated savings would be: for Gleevec they would pay $638, for MS and rheumatoid arthritis patients they would pay $628, and for someone taking Tracleer their annual cost would be $638.  For those between 100 and 135 percent of the FPL, they would pay at most $60 per year for any of the drugs covered in the demonstration program, and seniors below 100 percent of FPL could pay less.

"Seniors are going to save substantial money on their prescription medicines thanks to the new drug benefit under Medicare, and this demonstration will give them a sense of the savings that are on the way," Secretary Thompson said. "For seniors currently without drug coverage, this new benefit will help strengthen their health and their pocketbook. It provides substantial savings on the out-of-pocket costs they currently pay for medicines."

As directed by Congress in creation of the demonstration, approximately 40 percent of the funding will be allocated for oral anti-cancer medications. If more beneficiaries apply than Medicare is able to serve, CMS will select participants among the cancer and non-cancer groups randomly from the applications received, on an alternating basis between the two groups.

To be eligible for the demonstration, a beneficiary must be enrolled in Medicare Part A and Part B, Medicare must be their primary payer, and the beneficiary may not have comprehensive drug coverage through other sources (such as TriCare, Medicaid, or an employer or union sponsored plan). A beneficiary must also have a signed certification from a doctor that he or she requires one of the drugs covered under the demonstration for the indicated disease. 

"We intend to work with our state and local partners, and with patient organizations and others, to help beneficiaries with these serious diseases find out about how to take advantage of this program -- and about the additional help now available to assist with drug costs," Dr. McClellan said.

CMS is conducting an Open Door Forum on June 29 with patient advocacy groups, physician specialty groups, physicians and drug manufacturers so they can help beneficiaries in applying for the program.

To enroll in the demonstration program, beneficiaries should complete an application, get their physician to complete the required form certifying their need for the covered drug, and submit both forms to CMS’ demonstration contractor, TrailBlazer Health Enterprises.

Participants in the demonstration will be able to get their drugs at a local retail pharmacy or by home delivery through Caremark, Trailblazer’s subcontractor for administering the drug benefit.

The demonstration will run through Dec. 31, 2005, at which time all beneficiaries will be able to enroll in the new Medicare Part D drug benefit.

Starting immediately, applications may be downloaded from the CMS Web site at http://www.cms.hhs.gov/researchers/demos/drugcoveragedemo.asp.  Starting July 6, customer service representatives will be available at 1-866-563-5386, TTY Number: 1-866-536-5387 to answer questions about the demonstration and assist beneficiaries in obtaining and completing the application forms.  Between now and July 6, beneficiaries who have questions can call 1-800 MEDICARE. Applications will be accepted for consideration beginning July 6 through Sept. 30.

Those beneficiaries who are able to get their applications in by Aug. 16 will be in an "early selection" process that will give them coverage by Sept. 1.

Applications will be accepted through Sept.30, at which time another selection process will be held.  As long as the application is received by Sept.30, all applicants will have an equal chance to get into the demonstration.  If enrollment slots are still available, applications will continue to be accepted after that date. 

Contact: CMS Public Affairs
(202) 690-6145

Note: All HHS press releases, fact sheets and other press materials are available at http://www.hhs.gov/news.

Protein Shift Predicts Brain Cancer Grade, Recurrence, Patient Survival

A molecular change that occurs as brain tumors progress may give clinicians a way to more precisely evaluate tumor grade and more effectively predict time to recurrence and length of patient survival.

Tue 22-Jun-2004
Newswise — Study results published in the August issue of the journal Cancer reinforce previous findings that the laminin-8 genes and the resulting protein may be highly valuable targets in the fight against malignant brain tumors.

Researchers at Cedars-Sinai’s Maxine Dunitz Neurosurgical Institute report that over-expression of laminin-8 can be used as a predictor of a tumor’s grade, its potential for recurrence, and the patient’s length of survival. This follows their earlier findings that laminin-8 is up-regulated in the most aggressive brain tumors, glioblastoma multiforme (GBM), and that the gene promotes the tumor cells’ ability to invade neighboring tissue.

The thin “basement membrane” that lies beneath the surface layer of blood vessels contains proteins called laminins. Fifteen laminins have been identified to date. The Cedars-Sinai researchers found that during tumor progression, laminin-9, which is expressed weakly in normal brain tissue and low-grade glial tumors, switched to laminin-8, and the level of expression of the laminin-8 increased significantly, depending on brain tumor grade.

Gliomas develop from glial cells, which make up the supportive tissue of the brain. Different forms of gliomas are further classified by their specific cells of origin and characteristics. The average survival time for patients with Grade 1 or Grade 2 gliomas is six to eight years. For anaplastic astrocytomas (Grade 3 gliomas), survival time decreases to three years, and for Grade 4 astrocytomas, called glioblastoma multiforme (GBM), survival length typically ranges from 12 to 18 months. GBM cells proliferate uncontrollably, aggressively infiltrating nearby tissue. As a GBM progresses, portions of the tumor often outgrow the blood supply but new blood vessels form. The development of these new vessels, a process called angiogenesis, enables the tumor to grow unchecked.

In this study, Cedars-Sinai researchers, in conjunction with colleagues in Japan, Sweden and Germany, analyzed a variety of gliomas of both high and low grades, as well as normal brain tissue samples. Low-grade astrocytomas and normal brain tissue were found to express very low levels of laminin-9 and virtually no laminin-8. The levels of expression of both variants increased in Grade 3 gliomas, and as gliomas progressed to Grade 4, laminin-8 expression increased significantly and laminin-9 levels tended to decline.

The particular isoform (laminin-8 or laminin-9) predominantly expressed in Grade 4 gliomas appeared to correlate with time to recurrence after tumor-removal surgery. Among patients with high laminin-8 expression, tumors recurred about 4 months after surgery, compared with more than 11 months among patients whose tumors expressed laminin-9 predominantly. Patients with higher levels of laminin-8 also had shorter lengths of survival, averaging about 11 months, compared to 16.7 months when laminin-9 was predominant.

“Historically, the diagnosis of glioblastoma multiforme has come with an extremely poor prognosis, and traditional treatments have had very limited impact on patient survival,” said Keith L. Black, MD, director of the Maxine Dunitz Neurosurgical Institute, Cedars-Sinai’s Division of Neurosurgery and the Comprehensive Brain Tumor Program.

“Only in recent years have we begun to see progress, which is coming from a better understanding of genetic, molecular and immunologic changes that enable these deadly tumors to grow,” said Dr. Black, who holds the Ruth and Lawrence Harvey Chair in Neuroscience at the medical center. “Although a number of genes and proteins have been identified as having altered expression in glial tumors, few have become reliable indicators that can be used to improve diagnosis, prognosis and treatment.”

Julia Y. Ljubimova, MD, PhD, research scientist at the Institute and first author of the Cancer article, said the over-expression of laminin-8 may prove to be one of those important markers. Taken in consideration with other genes known to support tumor growth, it may give clinicians measurable clues for predicting recurrence and survival times of patients with high-grade gliomas.

“The switch from laminin-9 to laminin-8 expression, with its gradual increase from a low level of expression in low-grade tumors to a moderate level of expression in Grade 3 gliomas to a significantly high level of expression in 74 percent of GBMs, may be associated with the development of new tumor-feeding blood vessels, contributing to tumor aggressiveness,” she said. “Therefore, laminin-8 appears to be a promising marker of tumor progression. Perhaps more importantly, we hypothesize that if laminin-8 plays a major role in tumor progression and recurrence, it could be an important target for the development of new therapies.”

Cedars-Sinai is one of the largest nonprofit academic medical centers in the Western United States. For the fifth straight two-year period, it has been named Southern California's gold standard in health care in an independent survey. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthroughs in biomedical research and superlative medical education. It ranks among the top 10 non-university hospitals in the nation for its research activities.

Citation: Cancer, August 2004, “Association between Laminin-8 and Glial Tumor Grade, Recurrence, and Patient Survival.”

SciClone's ZADAXIN Shows Promising Effects in Treating Brain Cancer in Animal Model Study

SAN MATEO, Calif.--(BUSINESS WIRE)--June 15, 2004--SciClone Pharmaceuticals, Inc. (Nasdaq:SCLN) today announced the results of an animal model study evaluating its lead candidate ZADAXIN(R) in combination with carmustine (BCNU), a chemotherapy agent commonly used to treat brain tumors, as a potential therapy for glioblastoma multiforme (GBM), the most lethal form of brain cancer. Results from the study demonstrated that treatment with ZADAXIN plus BCNU led to significantly lower tumor burdens and increased cure rates as compared to treatment with BCNU alone. These results were presented today in an abstract at the 11th Annual International Symposium on Pediatric Neuro-Oncology conference in Boston, Massachusetts.

Dr. Suzanne de la Monte, a neuropathologist and Associate Professor of Pathology, and Dr. Jack Wands, Professor of Medicine and Director of the Liver Research Center, both of Brown University School of Medicine commented that they are excited about these data "that suggest the addition of thymosin alpha 1 (ZADAXIN) could significantly enhance the effectiveness of BCNU-mediated eradication of glioblastoma."

In addition, in vitro studies demonstrated that ZADAXIN served to increase both the levels of pro-apoptosis gene expression and tumor cell sensitivity to oxidative stress, thereby allowing the chemotherapeutic agent BCNU to function more effectively in destroying the cancerous cells.

About Glioblastoma multiforme (GBM)

The American Cancer Society estimates that in 2004 approximately 12,690 people will die from malignant tumors of the brain or spinal cord and 18,400 new cases will be diagnosed. Current treatment is inadequate as indicated by an average patient survival time of only 12 months. Treatment includes surgery, radiation therapy, and chemotherapy and has shown the ability to prolong patient survival. Glioblastoma is classified as a stage 4 malignant tumor and is considered to be the most common and aggressive of primary brain tumors.

About SciClone

SciClone Pharmaceuticals is a biopharmaceutical company engaged in the development of therapeutics to treat life-threatening diseases. SciClone is currently evaluating its lead product ZADAXIN in several clinical trials, including two phase 3 hepatitis C clinical trials in the U.S., a completed phase 3 hepatitis B clinical trial in Japan, a phase 2 malignant melanoma clinical trial in Europe, two phase 2 liver cancer pilot studies in the U.S., a hepatitis C triple therapy open-label clinical trial in Mexico, and a hepatitis B combination therapy trial in Taiwan. SciClone recently announced plans for a ZADAXIN phase 3 hepatitis C triple therapy clinical trial in Europe. The company's other principal drug development candidate is SCV-07, a potentially orally available therapeutic to treat viral and infectious diseases. For more information about SciClone, visit www.sciclone.com.

This press release may contain forward-looking statements because the experimental or clinical data described may imply certain actual results in larger patient populations. Experimental data and clinical results derived from studies with animals or a limited group of patients may not be predictive of the results of larger studies and, therefore, such experimental or clinical data is not necessarily predictive of efficacy or safety or the results of larger studies and clinical trials.

Drug appears to improve survival from brain cancer

Associated Press Thursday, June 10, 2004
NEW ORLEANS--Early low-dose chemotherapy appears to substantially improve short-term survival in patients with the most aggressive and common form of brain cancer, offering the first significant advance against the disease in decades.

Whether the treatment can help cure brain cancer remains to be seen, but the approach at least seems to slow the often rapid progression of the disease for some.

The treatment, tested on a form of brain cancer called glioblastoma multiforme, involves the drug Temodar. Until now, the medicine has typically been used only after radiation to shrink the tumor.

A major international study released this week shows that giving low doses of the capsule at the very start -- for six or seven weeks during and after radiation -- doubles the chance of being alive two years later.

"This is the first trial that has been clearly positive in brain cancer in 30 years," said Dr. M.J. van den Bent of the Daniel den Hoed Oncology Center in Rotterdam, the Netherlands. "This is a great day."

Radiation and surgery are the first-line treatments for glioblastomas, but even with them the disease usually kills within a year or less. Intravenous chemotherapy available since the 1970s improves these odds only marginally and can have serious side effects.

Several doctors predicted that upfront Temodar will quickly become the standard of care, routinely offered to all victims of this disease.

"To be able to tell people they may have two or three years of survival rather than nine months is pretty major," said Dr. Adam Mamelak of City of Hope National Medical Center in Duarte, Calif., who was not involved in the study.

Drug extends lives of people with brain cancer

By Marilynn Marchione

Milwaukee Journal Sentinel - Thu, Jun. 10, 2004
NEW ORLEANS - For the first time, a drug has been shown to meaningfully extend life in people with the most deadly and common form of brain cancer - the biggest advance in treating the disease in 30 years.

Patients given low, daily doses of temozolomide along with radiation treatment were more than twice as likely to be alive two years later as those who got radiation alone, a new study found.

Experts predicted that the drug will become widely used for this type of tumor and tried on other types, too.

"It would be my new standard of care," said Harmon Eyre, the American Cancer Society's chief medical officer, who was not involved in the research.

Results were reported Monday to the American Society of Clinical Oncology at a meeting of 25,000 cancer experts in New Orleans.

The study involved nearly 600 patients at 85 hospitals throughout Europe, Canada and Australia. Half got daily pills of temozolomide during radiation treatment and for six months afterward. The others got radiation alone.

After two years, 26 percent who got the drugs were alive, vs. 10 percent who got just radiation, said Roger Stupp, a doctor at University Hospital in Lausanne, Switzerland, who led the study.

"This drug has some particular chemical properties that allow it to get to the target better. Many drugs do not get to where you want them to go. It crosses the blood-brain barrier," Stupp said of temozolomide.

That barrier has been the main hurdle to treating brain tumors, one of the few types of cancer that kill while still locally confined but that defy treatments typically used for locally confined cancers, Eyre said.

Temozolomide good in 'early' brain cancer

Tuesday, June 8, 2004
NEW ORLEANS, Jun 08, 2004 (United Press International via COMTEX) -- Swiss scientists have shown for the first time adding chemotherapy to radiation treatment prolongs life for people with the most common brain cancer.

Dr. Roger Stupp of the University Hospital of Lausanne, Switzerland, studied 573 brain cancer patients in Europe, Canada and Australia who had glioblastoma multiforme, the most common and aggressive of brain tumors, the New York Times reported Tuesday.

It is usually treated by surgery followed by radiation therapy.

In Stupp's trial, those who received the drug temozolomide during and after the radiation therapy lived a median of 14.6 months, compared with 12.1 months among those who got the radiation alone.

After two years, 26 percent of those who got the drug were still alive, compared with 10 percent of those who only got radiation.

Temozolomide, sold by Schering-Plough as Temodal in Europe and Temodar in the United States, is usually used to treat recurrent brain cancers, rather than for initial treatment, as in this trial.

Stupp's work was reported Monday at the annual meeting of the American Society of Clinical Oncology meeting in New Orleans.

Copyright 2004 by United Press International.

Approach extends brain cancer survival

Study: Chemotherapy helps with aggressive form of disease
By Jacqueline Stenson, MSNBC

June 07, 2004 NEW ORLEANS - Adding chemotherapy to standard radiation treatment can boost survival for patients with an aggressive form of brain cancer that usually kills within months of diagnosis, new study findings show.

Nearly three times as many patients were still alive after two years with the combination treatment than with radiation alone, according to results presented here Monday at the annual meeting of the American Society of Clinical Oncology.

“This treatment clearly improved overall survival,” said study author Dr. Roger Stupp of the University Hospital Mutidisciplinary Oncology Center in Lausanne, Switzerland.

The patients had glioblastoma multiforme, the most common and most aggressive type of brain cancer that is considered incurable. It is diagnosed in about 18,400 Americans each year and kills nearly 13,000 annually.

“Patients usually die within less than one year,” Stupp said.

Chemotherapy can make a difference
Radiation treatment after surgery to remove a tumor has been the standard treatment for these patients for three decades, Stupp noted. The new findings are the first to show that chemotherapy can make a difference when given in combination with radiation.

“This will probably change the standard of care,” Stupp said.

While not a cure, he said, the findings offer new hope for a notoriously difficult and deadly cancer.

“These are pretty good-looking data,” commented Dr. Frank Haluska, a cancer specialist at Massachusetts General Hospital in Boston.

The study involved almost 575 patients, ages 18 to 70, treated at more than 80 centers in Europe, Canada and Australia. Half were given standard radiation treatment after surgery to remove their tumors, while the other half were given both radiation and chemotherapy with the oral drug temozolomide.

Results showed that 26 percent of patients who received chemotherapy survived at least two years, compared with 10 percent in the other group. Patients on chemotherapy also saw their disease progress more slowly.

'It is progress'
While a 26 percent survival rate may not seem terrific, Haluska noted, it’s nearly three times as long as with standard treatment, and for a very deadly disease.

“It is progress,” he said.

Stupp said the chemo drug was well-tolerated by patients, generally only causing “mild to moderate” side effects such as fatigue and nausea.

Another study presented at the meeting showed that chemotherapy may also help patients with less common brain cancers called gliomas.

Researchers in the United States and Canada found that adding the drugs procarbazine, lomustine and vincristine to radiation therapy slowed the advance of the disease, which took about 2.6 years to progress in this group versus 1.9 years in the group receiving radiation alone.

But the chemo combination did not prolong overall survival in the study of almost 300 patients, who lived a median of about 4.5 years, reported Dr. Gregory Cairncross of the University of Calgary.

However, patients with certain genetic mutations in chromosomes 1 and 19 lived longer, regardless of their treatment.

Medicare to Extend Access to Certain Drugs for Beneficiaries with Serious and Chronic Illnesses

FOR IMMEDIATE RELEASE Thursday, June 24, 2004
HHS Secretary Tommy G. Thompson today announced a new Medicare demonstration program that will save seniors and persons with disabilities substantial money -- up to 90 percent in some cases -- on the life-enhancing medicines they take for serious diseases, including cancer, multiple sclerosis and rheumatoid arthritis.

The demonstration program, created as part of the Medicare Modernization Act, will extend Medicare coverage to prescription medicines that can be self-administered rather than administered by a health care provider. The demonstration will help up to 50,000 beneficiaries with serious illnesses who do not have comprehensive prescription drug coverage today.

"This demonstration will provide access and affordability to life-saving medicines for people fighting serious diseases," Secretary Thompson said.  "Through this coverage, seniors will save thousands of dollars on essential medicines that they can take at home. It will relieve some of the burden of battling a debilitating disease."

The initiative, known as the Medicare Replacement Drug Demonstration, was mandated under Section 641 of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA). As set by Congress, enrollment in the demonstration will be open to 50,000 people and total spending on the covered drugs will be up to $500 million.

Under this initiative, Medicare will pay for certain drugs and biologicals that can be taken by the patient at home and that replace drugs which are currently covered under Medicare Part B when given in a doctor’s office.  In addition, newer, more effective medications that replace some currently covered oral anti-cancer drugs will also be covered.

"Covering drugs that you can administer yourself improves access to high-quality care", said Mark B. McClellan, M.D., Ph.D., administrator of the Centers for Medicare & Medicaid Services (CMS). "In some cases, by avoiding the need for doctor visits and intravenous injections, costs and medical complications may be reduced and access and ease of treatment will increase. And many beneficiaries will get literally tens of thousands of dollars worth of help in purchasing these critical medicines right away, ahead of the Medicare drug benefit in 2006."

Drugs for treatment of such diseases as rheumatoid arthritis, multiple sclerosis, pulmonary hypertension and a variety of cancers will be included in the demonstration. The drugs were selected based on criteria developed after extensive input from physicians and other experts.  The drugs and the diseases that are covered are listed below.

Beneficiary cost sharing for these drugs will mirror the "standard" Medicare Part D prescription drug benefit when it is implemented in 2006 (participants will not pay the monthly premium in the demonstration, however).  Beneficiaries with limited resources and incomes of less than 150 percent of the federal poverty level (FPL) will have even lower cost sharing requirements.

The demonstration will give Medicare beneficiaries a glimpse of the significant savings coming their way when the Part D prescription drug benefit is fully implemented in 2006.

Examples of estimated savings over a year include:

• Patients with Chronic Myelogenous Lymphoma (a cancer) using Gleevec could save nearly 90 percent or $40,654 annually. Gleevec has an estimated annual cost of $45,952, but patients in the demo would o

nly pay $5,298.

• Patients with Multiple sclerosis could save 75 percent or $12,260 annually off medicines that cost an estimated $16,298 annually. They would pay only $4,038.

• Patients with rheumatoid arthritis could save 75 percent or $11,975 annually off medicines that cost an estimated $16,000. They would pay only $4,025.

• And patients with pulmonary hypertension using Tracleer could save 86 percent or $31,255 off of a cost that otherwise could reach $36,136. They would pay only $4,881.

Low–income beneficiaries in the demonstration would save significantly more.  Using the above examples, for those between 135 and 150 percent of the FPL estimated savings would be: for Gleevec they would pay $638, for MS and rheumatoid arthritis patients they would pay $628, and for someone taking Tracleer their annual cost would be $638.  For those between 100 and 135 percent of the FPL, they would pay at most $60 per year for any of the drugs covered in the demonstration program, and seniors below 100 percent of FPL could pay less.

"Seniors are going to save substantial money on their prescription medicines thanks to the new drug benefit under Medicare, and this demonstration will give them a sense of the savings that are on the way," Secretary Thompson said. "For seniors currently without drug coverage, this new benefit will help strengthen their health and their pocketbook. It provides substantial savings on the out-of-pocket costs they currently pay for medicines."

As directed by Congress in creation of the demonstration, approximately 40 percent of the funding will be allocated for oral anti-cancer medications. If more beneficiaries apply than Medicare is able to serve, CMS will select participants among the cancer and non-cancer groups randomly from the applications received, on an alternating basis between the two groups.

To be eligible for the demonstration, a beneficiary must be enrolled in Medicare Part A and Part B, Medicare must be their primary payer, and the beneficiary may not have comprehensive drug coverage through other sources (such as TriCare, Medicaid, or an employer or union sponsored plan). A beneficiary must also have a signed certification from a doctor that he or she requires one of the drugs covered under the demonstration for the indicated disease. 

"We intend to work with our state and local partners, and with patient organizations and others, to help beneficiaries with these serious diseases find out about how to take advantage of this program -- and about the additional help now available to assist with drug costs," Dr. McClellan said.

CMS is conducting an Open Door Forum on June 29 with patient advocacy groups, physician specialty groups, physicians and drug manufacturers so they can help beneficiaries in applying for the program.

To enroll in the demonstration program, beneficiaries should complete an application, get their physician to complete the required form certifying their need for the covered drug, and submit both forms to CMS’ demonstration contractor, TrailBlazer Health Enterprises.

Participants in the demonstration will be able to get their drugs at a local retail pharmacy or by home delivery through Caremark, Trailblazer’s subcontractor for administering the drug benefit.

The demonstration will run through Dec. 31, 2005, at which time all beneficiaries will be able to enroll in the new Medicare Part D drug benefit.

Starting immediately, applications may be downloaded from the CMS Web site at http://www.cms.hhs.gov/researchers/demos/drugcoveragedemo.asp.  Starting July 6, customer service representatives will be available at 1-866-563-5386, TTY Number: 1-866-536-5387 to answer questions about the demonstration and assist beneficiaries in obtaining and completing the application forms.  Between now and July 6, beneficiaries who have questions can call 1-800 MEDICARE. Applications will be accepted for consideration beginning July 6 through Sept. 30.

Those beneficiaries who are able to get their applications in by Aug. 16 will be in an "early selection" process that will give them coverage by Sept. 1.

Applications will be accepted through Sept.30, at which time another selection process will be held.  As long as the application is received by Sept.30, all applicants will have an equal chance to get into the demonstration.  If enrollment slots are still available, applications will continue to be accepted after that date. 

Contact: CMS Public Affairs
(202) 690-6145

Note: All HHS press releases, fact sheets and other press materials are available at http://www.hhs.gov/news.

Temozolomide good in 'early' brain cancer

Tuesday, June 8, 2004
NEW ORLEANS, Jun 08, 2004 (United Press International via COMTEX) -- Swiss scientists have shown for the first time adding chemotherapy to radiation treatment prolongs life for people with the most common brain cancer.

Dr. Roger Stupp of the University Hospital of Lausanne, Switzerland, studied 573 brain cancer patients in Europe, Canada and Australia who had glioblastoma multiforme, the most common and aggressive of brain tumors, the New York Times reported Tuesday.

It is usually treated by surgery followed by radiation therapy.

In Stupp's trial, those who received the drug temozolomide during and after the radiation therapy lived a median of 14.6 months, compared with 12.1 months among those who got the radiation alone.

After two years, 26 percent of those who got the drug were still alive, compared with 10 percent of those who only got radiation.

Temozolomide, sold by Schering-Plough as Temodal in Europe and Temodar in the United States, is usually used to treat recurrent brain cancers, rather than for initial treatment, as in this trial.

Stupp's work was reported Monday at the annual meeting of the American Society of Clinical Oncology meeting in New Orleans.

Copyright 2004 by United Press International.