konisys Inc., a New Haven, Conn.-based developer of automated cell-based diagnostic products, announced in January that the FDA cleared the company’s bladder cancer diagnostic test oncoFISH™ Bladder for marketing in the US. The diagnostic application, together with the company’s robotic digital microscopy platform, aids in the detection of bladder cancer by  automated testing of cells found in urine specimens.

	Ikonisys’ products automate a time-consuming laboratory technique called fluorescence in situ hybridization (FISH), which is used routinely to identify chromosomal abnormalities associated with various diseases. The oncoFISH bladder application looks for abnormalities in chromosomes 3, 7, 9, and 17 in the cells found in urine sediment. The goal of the test is initial diagnosis of bladder cancer in patients with hematuria (blood in the urine) and monitoring for tumor recurrence in patients who have been diagnosed with bladder cancer.

	Petros Tsipouras, the Chariman and CEO of Ikonisys said that “oncoFISH bladder is expected to significantly reduce the time required to process test results while improving the accuracy of bladder cancer diagnosis.”

string of important announcements have recently come from Tustin, CA-based Peregrine Pharmaceuticals, Inc., a biopharmaceutical company developing targeted therapeutics for the treatment of cancer, positively confirming the value of the company’s proprietary technology in China’s growing market even as the company handles a domestic lawsuit.

	On January 18, Peregrine reported that Shanghai Medipharm Biotech (Medipharm) has launched an iodine-131 labeled Tumor Necrosis Therapy (TNT) antibody for lung cancer treatment in the People’s Republic of China. Earlier in January, Peregrine  reported that it has filed a lawsuit alleging breach of contract against its licensee Cancer Therapeutics Laboratories, Inc. (CTL), a California company that licensed certain rights to Peregrine’s TNT platform for development and commercialization in China. Peregrine also simultaneously announced that it has established a wholly foreign-owned enterprise, Peregrine Beijing Pharmaceuticals Technology Development Ltd., in Beijing.

	Peregrine’s TNT anti-cancer platform consists of therapeutic radioactive isotopes attached to monoclonal antibodies that are specifically designed to bind to a type of DNA that is exposed on the dead and dying  TNT compound targets tumors and delivers its anti-cancer radioactive agent to the center of the mass, killing the tumor from the inside out and avoiding damage to the surrounding healthy tissue. The TNT platform also includes the investigational drug Cotara®, which is undergoing phase II trials for treating malignant brain tumors (glioblastoma multiforme) in the US and India.

	In 2003, Medipharm reported results of a clinical study of advanced lung cancer patients in China. After treatment with the TNT agent, 4% of patients underwent complete remissions, almost 31% has partial remissions involving more than 50% tumor shrinkage, 55% experienced no change in their tumor masses, and about 10% showed progressive disease. These  encouraging results prompted a market launch of the treatment in China.

	But the Chinese company is in a sublicense agreement with CTL, which had licensed certain rights to Peregrine’s TNT  technology, and is now being sued by Peregrine under various alleged breaches of contract. The lawsuit was filed in the Superior Court of the State of California for the County of Orange against CTL and cites breaches of contract that include: failing to provide sufficient clinical data to Peregrine regarding the TNT agent; failure to account for an alleged sublicense agreement with Medipharm despite repeated attempts by Peregrine to obtain evidence of such an agreement; and failure to provide any substantive accounting of revenue, equity and data obtained from the above purported sublicense agreement.

	Following the CTL lawsuit, Peregrine is exploring options regarding other avenues for the technology’s commercialization in China. The company plans to pursue development and commercialization on its own through its new wholly owned subsidiary in Beijing.

iopharmaceutical company Introgen Therapeutics Inc., located in Austin, TX, has reported positive news on two of its targeted molecular therapeutic products for the treatment of cancer.

	First, the company was invited to present biomarker data on its ADVEXIN p53 tumor suppressor therapy, which is now  undergoing phase III clinical trials for head and neck cancer treatment, at an international cell and gene therapy conference.

	Introgen’s ADVEXIN therapy combines the p53 tumor suppressor gene with a nonreplicating adenoviral gene delivery system. The company has previously reported that for recurring head and neck cancers, the therapy leads to tumor responses and median survival rates comparable to those obtained with other more toxic therapies. The new expanded biomarker studies show that recurrent head and neck cancer patients with the abnormal p53 biomarker had the most survival benefits when treated with ADVEXIN and least likely to benefit from conventional therapies. Patients with tumors abnormally expressing the p53 biomarker had a median survival of11.6 months, while the other patients had a median survival of 3.5 months. Further, tumor control was seen in 75% of the patients with the abnormal biomarker; in patients without the biomarker, 18% experienced tumor control. Introgen is currently seeking to register the therapy in the US and Europe and plans to use the updated biomarker studies to help in obtaining licensure.

	The other good news came for the company’s INGN 241 therapy in a preclinical study done at the MD Anderson Cancer Center, which showed INGN 241 in combination with Avastin® resulted in complete lung cancer tumor inhibition and regression.

	Like the ADVEXIN therapy, INGN 241 also employs a tumor suppressor gene called the mda-7 gene, which induces cell death. The new study published in 

showed that the combination of INGN 241 and Avastin blocked the formation of new blood vessels in a tumor very effectively—tumors completely regressed within the first four weeks of therapy. In contrast, when the animals were treated only with Avastin, they experienced minor tumor regression and the tumors were not eradicated.

	INGN 241 is currently being tested in phase III clinical trials combined with radiation therapy for the treatment of head and neck tumors.

Debiopharm Procures Cancer Therapy from Kirin Brewery

ebiopharm will gain exclusive rights for the development and commercialization of Debio-0719, an LPA inhibitor. The drug, which was discovered by Kirin Brewery, has applications as a therapy for local and metastatic cancer. Kirin will maintain these rights in Asia, and relinquish the rest to Debiopharm.

	Kirin Brewery signed a deal with Debiopharm, a biopharmaceutical development company that specializes in oncology. The deal is an exclusive research and development and commercialization agreement for Debio-0719, a local and metastatic cancer therapy. Under the terms and agreements, Debiopharm will be responsible for all aspects of the development of Debio-0719. After the development, Debiopharm maintains the rights to out-license the therapy to sales and marketing  partners, excluding Asia where Kirin will keep both development and commercialization rights. Kirin will also be eligible for milestone payments, as well as royalties based on Debiopharm’s sales.

	Debio-0719 is an inhibitor of Lysophosphatidic acid (LPA) signaling. LPA plays an important role in controlling tumor growth through signal transduction pathways, which makes it a significant target against cancer. Debio-0719 is currently being tested in preclinical trials against local and metastatic cancer.

	Debiopharm has successfully developed and marketed two cancer therapies. Decapeptyl® is a luteinizing hormone releasing hormone agonist, which can be used to treat sex hormone-dependent diseases, including prostate cancer. The company has also developed Eloxatin®, an anticancer chemotherapeutic. The drug is a part of the platinum complex series, which targets testicular, ovarian, bladder, and lung carcinomas.

Articles

Additional breaking news from the biotech industry. In this issue:  1) FDA OKs Ikonisys' Bladder Cancer Test 2) Good News From China for Peregrine 3) Introgen Sees Advances on Two Fronts 4) Debiopharm Procures Cancer Therapy from Kirin Brewery 

The Industry Insider: March 2007

National Human Genome Research Institute Announces Genome Sequencing Centers

	for The Cancer Genome Atlas Pilot Project

he announcement of the fourth and final component of The Cancer Genome Atlas (TCGA) Pilot Project came on November 20, when the National Human Genome Research Institute (NHGRI) designated three leading research and cancer centers as TCGA Genome Sequencing Centers. The Genome Sequencing Centers (GSC) form one of four integrated components of the TCGA Pilot Project. The others, seven Cancer Genome Characterization Centers, the Data Coordinating Center, and the Biospecimen Core Resource were announced earlier. (see the last issue of 

 for more at http://www.nxtbook.com/nxtbooks/intellisphere/obn1106/.)

	The NHGRI and the National Cancer Institute announced that the three sequencing centers will devote a significant part of their DNA sequencing efforts to the TCGA project, strengthening the project’s endeavors to identify the genomic changes involved in three types of tumors: brain (glioblastoma), lung, and ovarian.

	The three GSCs are the Broad Institute of MIT and Harvard University, the Genome Sequencing Center at the Washington University School of Medicine in St. Louis, and the Human Genome Sequencing Center at Baylor College or Medicine. These research centers were selected from more than 20 organizations and institutes that have contributed to the Human Genome Project. For fiscal year 2007, the NHGRI has awarded these centers funds of $48 million, $41 million and $27.6 million respectively.

	The centers will be responsible for sequencing several genes and selected genomic targets that are identified by two separate approaches. The first will be “genes of interest” such as tumor repressors or oncogenes that are identified from scientific literature and by consultation with oncology experts. The other will be genes and genomic regions that the TCGA’s Cancer Genome Characterization Centers identify as candidates. To conduct these sequencing activities, the centers will receive quality-controlled samples of tumor specimens from the Human Cancer Biospecimen Core Resource.

	The GSCs are also expected to test and implement a number of new technologies to increase the speed and bring down the cost of DNA sequencing. The long-term goal is to sequence the entire genome of individual tumor samples.

	The centers “will play a pivotal role in our systematic effort to assess the range of genomic changes associated with malignancy,” said Mark Guyer, director of NHGRI’s Division of Extramural Research. “This genomic information will provide the research community with a powerful tool for uncovering new therapeutic targets and developing better strategies for diagnosing, treating and preventing cancer.”

	Visit the TCGA website’s page on Genome Sequencing Centers at http://cancergenome. nih.gov/components/gsc.asp.

                                                                                                                                                                                                      —Prachi Patel 

Several States and Washington, DC Taking Lead in Promoting Cervical Cancer Vaccination

ore than half a dozen states and Washington, DC have introduced legislation that would mandate middle-school age girls to receive a vaccine against the human papilloma virus (HPV), a known cause of cervical cancer. Some states have announced plans to make Merck’s Gardasil vaccine available at no cost—the full regimen of three shots over six months costs $360. Many states offer parents and guardians the choice to opt out of the requirement.

	In clinical trials on more than 11,000 girls and women worldwide, Gardasil has been shown to be 100% effective in preventing infection with HPV strains 16 and 18, which together cause about 70% of cervical cancer cases. It also protects against vaginal and vulvar cancers, which are linked to HPV, according to the American Society of Clinical Oncology. Gardasil received its first validation in July 2006 when the FDA approved the vaccine for sale to girls and women ages nine to 26. The CDC followed close on the heels of the FDA’s decision when its Advisory Committee on Immunization Practices recommended that girls ages 11 and 12 receive the vaccine. Then came yet another reinforcement, this time from the American Cancer Society, which published its guidelines for the vaccine in the January 19, 2007 issue of its journal 

	But even as proponents are commending efforts by US states as a critical step in the fight against cervical cancer, the initiative has drawn fire from critics. Groups who oppose government vaccine requirements as well as many social conservatives are saying that giving Gardasil to young girls could encourage sexual promiscuity. The issue is further complicated because of social and racial issues—a disproportionately high number of cases are found to occur in minority and low-income women.

	Whether or not the above states pass their respective bills, many health experts and advocates support the idea and see this as the right step towards combating the deadliest cancer to afflict women. According to the ACS, more than 11,000 women will be diagnosed with cervical cancer in 2007 and about a third of those women will die from the disease. The new vaccines,  combined with information about the viral causes of cervical cancer, “present and unprecedented opportunity for global cervical cancer prevention,” the ACS guidelines say.

	In the seven months since the FDA approved Gardasil sales, there has been a flurry of HPV vaccine-related legislative actions at the state level. Here is a recap of these actions:

	In December, the California Assembly Speaker introduced a bill that would require all girls in the state entering sixth grade to receive a HPV vaccine. The bill would allow girls to be exempted if their parents file a letter saying that participation is against their beliefs.

	A bill recently presented in the state legislature would require girls 12 and older to either show proof that they received Gardasil or that their parents have declined the immunization.

	The new year for Kentucky started with a newly introduced bill that would require girls in public and private middle schools to receive an HPV vaccination. Kentucky law states that immunizations are not required for “any child whose parents are opposed to medical immunization against disease and who object by a written sworn statement to the immunization of such child on religious grounds.”

	In early January, the state planned to begin distributing Gardasil to doctors as part of its plan to provide the vaccine at no cost to female minors between 11 and 18 years of age. The state health department estimates that about 17,000 girls will receive Gardasil over the year. Some doctors will offer the vaccine on a first-come, first-serve basis while others will use waiting lists.

	The state Governor announced on January 8 that the state will provide Gardasil at no cost to girls ages 11 to 18, making it the second state after New Hampshire to provide the vaccine for free. About 44,000 girls in the state are eligible for the vaccine, and the state had plans to distribute enough vaccines to physician offices and health department clinics by January 22. In the future, the state health department plans to focus on girls ages 11 and 12.

	On January 9, 2007, two DC city council members proposed a bill that would require girls entering the sixth grade to receive Gardasil. They would have to show proof of vaccination before enrolling in DC public schools, unless their parents or guardians opted out of the requirement. At 13.5 cases per 100,000 females, the cervical cancer rate in DC is much higher than the national average of 8.8. The Maryland senate and the Virginia General Assembly saw similar bills the week following the DC bill introduction.

	The state has the second highest cervical cancer mortality rate, after Washington, DC, with four women in 100,000 dying of the disease every year. On January 17, a state delegate announced that she would be introducing a bill that would mandate all girls to receive Gardasil by sixth grade. Georgia, New Jersey and Texas are now considering similar initiatives.

                                                                                                                                                                                                            —Prachi Patel 

Cervical Cancer Vaccine Sparks Scientific, Social Debate

Scientists and society disagree over routine HPV vaccination of girls and women

either leading cancer authorities nor the general public completely agree over whether and when girls and women should receive a new vaccine thought to prevent the most common forms of human papillomavirus (HPV). Left untreated, the sexually transmitted virus can develop, over time, into cervical cancer, considered one of the more preventable and curable of all cancers.

	The latest wrinkle in the vaccine debate came from the American Cancer Society, which recently said that, while it agrees with other cancer researchers that the vaccine is most effective when administered to girls as young as age nine, it does not agree the vaccine, Gardasil (quadrivalent human papillomavirus types 6, 11, 16, 18, recombinant vaccine) from Merck & Co., is effective in protecting women between the ages of 19 and 26 years old.

	“There are currently insufficient data to recommend for or against universal vaccination of females age 19 to 26 years in the general population,” according to the January/February 2007 issue of

. The ACS cited the article in their Jan. 19th position statement on the vaccine. “A decision about whether a woman age 19 to 26 years should receive the vaccine should be based on an informed discussion between the woman and her health care provider regarding

	her risk of previous HPV exposure and potential benefit from vaccination.”

	The ACS position is in conflict with several other recognized health authorities. The Food and Drug Administration approved the vaccine for use in girls and women ages nine through 26 years of age in early June. Later the same month, a US Centers for Disease Control Advisory Committee on Immunization Practices (ACIP) agreed with the FDA, saying women up to 26 years of age would still benefit from getting the vaccine. The Society of Gynecologic Oncologists concurred, supporting the ACIP’s recommendation for vaccinating women up to age 26, ideally before the onset of sexual activity. The American College of Obstetricians and Gynecologists also agreed with the ACIP recommendations.

	In addition to the scientific debate, there is societal debate over routine administration of the vaccine. Twenty-one states and the District of Columbia have reportedly already introduced legislation that would make the HPV vaccine mandatory for school-age girls, adding it to the list of other vaccines mandatory for school attendance. While most of these bills include a parental “opt-out” provision for the HPV vaccine, some parents resist the bill on principle. Several conservative religious groups, while supporting the availability of the vaccine for older women, say making the vaccine mandatory for school-aged children  undermines what they feel is the only way to avoid contracting HPV—abstinence. Some women’s health advocates say the vaccine may unintentionally cause women to skip routine PAP screenings, which they should continue to receive with or without the vaccine. Finally, the cost of the vaccine also concerns some groups. Gardasil must be administered three times over a six-month period at a cost of $120.00 per dose, which advocates for poor and uninsured women and children say puts it out of their reach.

                                                                                                                                                                                                           —Diane West

Cancer Deaths Drop, But So Do Mammography Screenings

t the same time they were cautiously celebrating a dramatic and historic drop in death rates from breast and other cancers in the United States, cancer researchers found themselves scratching their heads over the decline in the number of women  getting annual mammography screenings in recent years.

	The percentage of women over 40 who received an annual mammogram, considered a key component in detecting breast cancer in its earliest, treatable stages, dropped from 76.4 percent in 2000 to 74.6 percent in 2005, according to a US Centers for Disease Control report issued at the end of January. The data was gathered during a national telephone survey conducted from 2000 to 2005.

The Politics and Policy page provides a concise and timely round-up of key government-related oncology and biotechnology news. Content is focused upon the public sector activities that are most likely to impact the evolving oncology and biotech industries.

By Prachi Patel

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The Industry Insider: March 2007

Politics & Policy: March 2007