MonoSol Rx, the developers of PharmFilm(R) technology and a drug delivery company specializing in dissolving thin film pharmaceutical products, announced that the new drug application (NDA) for ondansetron orally dissolving film strip (ODFS) has been accepted for review by the U.S. fda.gov/” rel=”nofollow”>Food and Drug Administration (FDA). Ondansetron ODFS was developed using MonoSol Rx’s proprietary PharmFilm(R) technology to deliver the anti-emetic therapy ondansetron in a thin film strip that rapidly dissolves on the tongue.

MonoSol Rx and its partner Strativa Pharmaceuticals, the proprietary products division of Par Pharmaceutical Companies, Inc. (NYSE: PRX), are seeking FDA approval of ondansetron ODFS for the prevention of nausea and vomiting associated with highly- and moderately-emetogenic chemotherapy, radiotherapy and surgery. The NDA is supported by positive data from successfully completed pivotal bioequivalence studies against ondansetron ODT (orally disintegrating tablets), both with and without water. Pursuant to Prescription Drug User Fee Act (PDUFA) guidelines, the FDA is expected to respond to the NDA by the first quarter of 2010.

A. Mark Schobel, president and chief executive officer of MonoSol Rx, stated, “The FDA’s acceptance of the NDA for our ondansetron orally dissolving film strip further validates the acceptance of thin film as a new prescription dosage form. With our licensing partner Strativa we are one step closer to providing a promising new formulation of an anti-emetic therapy that leverages our PharmFilm(R) drug delivery technology. By delivering the drug orally through a rapidly dissolving film strip that requires no water, ondansetron ODFS has advantages over tablets or liquid medications, which can exacerbate nausea in these patients.”

The anti-emetic market totaled 4.1 million prescriptions in 2008. Ondansetron was the prescription leader in the category, accounting for 95% of prescriptions.

About MonoSol Rx

MonoSol Rx is a specialty pharmaceutical company leveraging its proprietary PharmFilm(R) technology to deliver drugs in quick dissolving films. PharmFilm(R) is designed to benefit patients by improving the convenience, efficacy, and compliance of new and currently marketed drugs. The Company’s leadership in thin film drug delivery is supported by strong intellectual property, a portfolio of commercialized over-the-counter (OTC) drug products, and a development pipeline of prescription formulations based on PharmFilm(R) technology. With a vertically integrated development and production infrastructure, MonoSol Rx has the capacity to manufacture OTC drug products for near-term revenues that fund prescription product development programs that will generate long-term value.

The Company’s commercialization strategy for all PharmFilm(R) products is to partner with the innovator, other specialty pharma or leading consumer products companies that can sell-in and manage product sales and marketing. For existing and future partners, PharmFilm(R) formulations represent revenue-life cycle extensions for products with patent lives that have expired or are approaching expiration. PharmFilm(R) is also a tool to help sales and marketing partners differentiate in competitive markets while offering unique advantages over drugs dosed by traditional tablets, capsules and orally disintegrating tablets (ODTs).

About Strativa Pharmaceuticals

Strativa Pharmaceuticals is the proprietary products division of Par Pharmaceutical, Inc. Strativa is committed to developing and marketing novel prescription drugs. Its initial focus is on supportive care therapeutics in HIV and oncology. Drawing on the specialty products expertise of its staff, Strativa possesses the resources to prepare products for commercialization and to help ensure their success after launch.

About Par Pharmaceutical

Par Pharmaceutical, Inc. develops, manufactures and markets generic drugs and innovative branded pharmaceuticals for specialty markets.

Source: MonoSol Rx

Although most gallbladder (GB) polyps are benign, some early carcinomas of the GB share the same appearance as benign polyps. Currently, GB polyps larger than 1 cm should be surgically removed because of the increased risk of malignancy. On the other hand, patients with smaller polyps usually require repeated US and follow-up. Distinguishing among non-neoplastic, neoplastic, and potentially malignant lesions is a major diagnostic dilemma, and the therapeutic options for these lesions remain controversial.

A research article published in the World Journal of Gastroenterology addresses this problem.

EUS is considered to be superior to conventional US for imaging GB lesions, because EUS can provide high-resolution images of small lesions at higher ultrasound frequencies (7.5-12 MHZ vs 3.5-5 MHz). Many studies have investigated the relationship between the neoplastic nature of GB polyps and their morphological characteristics such as the number of polyps, the polyp shape, the diameter of the largest polyp, the echo level and internal echo pattern, and the polyp margin. Among these variables, size is the most significant predictor of neoplastic polyps.

EUS could not differentiate malignant lesions from benign polyps less than 1.0 cm in size, because such small polyps do not often show findings typical of cholesterol polyps, localized types of adenomyomatosis, or neoplastic lesions. Thus, EUS alone is not sufficient for determining a treatment strategy for benign polypoid lesion of less than 1.0 cm.

Reference: Cheon YK, Cho WY, Lee TH, Cho YD, Moon JH, Lee JS, Shim CS. Endoscopic ultrasonography does not differentiate neoplastic from non-neoplastic small gallbladder polyps. World J Gastroenterol 2009; 15(19): 2361-2366

Correspondence to: Dr. Young Koog Cheon, Institute for Digestive Research and Digestive Disease Center, Soon Chun Hyang University College of Medicine, 657 Hannam-Dong, Yongsan-Ku, Seoul 140-743, South Korea.

Source:
Jian-Xia Cheng

World Journal of Gastroenterology

Researchers have found links between an individual’s genetics and their response to treatment with chemotherapy. The findings, by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues, show how a genetic variation, located in the SOD2 gene, may affect how a person responds to the chemotherapy drug cyclophosphamide. Cyclophosphamide is used in the treatment of breast and other cancers.

The SOD2 gene produces a key protein that protects cells from damage by molecules known as reactive oxygen species, or free radicals. Reactive oxygen species are produced by normal cellular processes and the action of some chemotherapy drugs. The findings represent the first preliminary evidence pointing toward a mechanism and a potential biomarker for cyclophosphamide resistance in breast cancer patients. The study appeared online June 9, 2009, in Clinical Cancer Research.

“This study shows how, with the progress of individualized medicine, a diagnostic test may be developed that determines whether a patient has certain genetic variations that may modify the effect of certain chemotherapies,” said study author Sharon Glynn, Ph.D., of NCI’s Center for Cancer Research.

“In the future, such tests may be used to guide the treatment of patients with the SOD2 variation, ensuring that they receive a therapy that is more effective than cyclophosphamide-based therapies,” added senior author Stefan Ambs, Ph.D., also of the Center for Cancer Research.

Most genes in human cells are present in two copies-one inherited from the mother and the other inherited from the father. These gene copies can vary from one another. Some variations in genes play an important role in how a gene is expressed or how its protein product functions.

The variant identified by the researchers in the SOD2 gene affects both the structure and the function of the encoded protein, an enzyme known as manganese superoxide dismutase (MnSOD) and affects the ability of MnSOD to reach its proper location in the cell and its activity level. MnSOD normally functions inside cellular compartments known as mitochondria and helps protect cells from damage caused by reactive oxygen species formed during cellular metabolism. Excessive levels of reactive oxygen species can be toxic to cells. Indeed, some anticancer drugs depend on increased production of reactive oxygen species to kill cancer cells. Furthermore, some studies have indicated that, because MnSOD neutralizes reactive oxygen species, it can modify the effects of chemotherapy drugs. For example, in laboratory and animal models, increased activity of MnSOD protects cells against the toxic effects of doxorubicin, which is a widely used anticancer drug.

In the new study, the research team investigated whether the variation affected survival in two separate groups of women with breast cancer: 248 women in the United States and 340 women in Norway. Some of the women received chemotherapy, and some did not receive chemotherapy. The team first analyzed DNA from the women to determine their genotype, meaning which types of the SOD2 gene they had. The researchers found that, among patients who received chemotherapy, those who had one form had decreased survival and those with another form had the poorest survival. In contrast, the genotype of SOD2 did not affect survival among those who did not receive chemotherapy.

Next, the team looked at the relationship between SOD2 genotype and the type of chemotherapy the women received. The data were analyzed according to which of three types of commonly used chemotherapy drugs were administered: doxorubicin, 5-fluorouracil, or cyclophosphamide. Both doxorubicin and cyclophosphamide generate reactive oxygen species in cancer cells during treatment. The researchers determined that the presence of a particular variant was associated with decreased survival of patients treated with chemotherapy regimens that contained any of the three drugs. However, the most significant effects were found with the drug cyclophosphamide. Women with a distinct variant form of SOD2 and who received cyclophosphamide-containing chemotherapy had the poorest survival.

The research team says more work is necessary to confirm these findings and to examine the precise mechanism by which a genotype influences the response of cancer cells to cyclophosphamide. The team plans to examine the influence of several variations on the resistance to other chemotherapies.

For more information on Dr. Ambs’ research, please go here.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Reference: Glynn SA, Boersma BJ, Howe TM, et al. A Mitochondrial Target Sequence Polymorphism in MnSOD Predicts Inferior Survival in Breast Cancer Patients Treated with Cyclophosphamide. Online June 9, 2009. Clinical Cancer Res.

Source
National Cancer Institute