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Biotechnol Healthc. 2010 Summer; 7(2): 10–11.
PMCID: PMC2899800

Clinical Trials, Research, and FDA Actions

Amy Krajacic, Senior Editor

Late-stage successes

A phase 3 trial of Sanofi-Aventis’ lixisenatide (Lantus) found that once-daily doses of the glucagon-like peptide-1 agonist improved glycemic control in patients with type 2 diabetes, as well as reduced glucose levels. The 12-week trial involved 361 patients who were not currently receiving any glucose-lowering therapy and who had hemoglobin A1c (HbA1c) between 7 percent and 10 percent. HbA1c was significantly reduced in patients who received lixisenatide, with levels below 7 percent found in 46.5 percent to 52.2 percent of treated patients. Fasting plasma glucose also was improved and a pronounced decrease seen in 2-hour post-prandial glucose excursion.

Amgen investigators have used banked patient tumor samples from a randomized, phase 3 trial of panitumumab (Vectibix) to determine which colorectal cancer patients may respond best to the drug. Tumor samples from 288 patients were tested for mutations in nine genes. Investigators found that patients with KRAS mutations received no beneficial effects from the panitumumab, while those with wild-type KRAS mutations did.

Trial disappointments

Pfizer has terminated another trial of its monoclonal antibody figitumumab after failing to show any significant endpoint results. The drug was studied in conjunction with erlotinib (Tarceva) as a second/third-line treatment for patients with previously treated advanced nonadenocarcinoma nonsmall cell lung cancer. The discontinuation also was recommended by an independent safety monitoring committee after it became apparent that figitumumab in combination with erlotinib was unlikely to be superior to erlotinib alone in improving overall survival within the study population.

Human Genome Sciences’ belimumab (Benlysta), an experimental lupus drug, failed to meet its secondary endpoints in a late-stage trial. The BLISS-76 study sought to evaluate belimumab versus placebo, with both given in combination with standard therapies. The belimumab combination failed to show statistically significant improvement at 76 weeks. Although patients did show improvement at 52 weeks, the study’s main goal, the chronic nature of lupus makes long-term efficacy ideal.

Did you hear?

Researchers at Stanford University in California have implanted an inorganic device into a cell wall without causing damage to it, offering potential access for seeing the way cells communicate with each other. Current methods of probing a cell are so destructive that they usually allow only a few hours of observation before the cell dies, but the 600-nanomater-long metal-coated silicon probe was designed to slip into a cell wall and fuse with it, mimicking natural gateways. The design was based on a type of protein naturally found in cell walls that acts as a gatekeeper. The next step is to determine the probe’s functionality in living cells; researchers are currently examining human red blood cells and cervical cancer cells, as well as hamster ovary cells. With further study, the hope is that the probe might one day serve as a conduit for inserting medications into a cell’s guarded interior or provide an improved method of attaching neural prosthetics. The research was published in a recent issue of the Proceedings of the National Academy of Sciences.

In other nanotechnology news, researchers at Scotland’s University of Edinburgh have used implantable gold nanosensors, along with a laser light, to detect proteins within cells that could one day enable easy and highly sensitive monitoring tools for blood clots and other disorders. Aptamers, or short strands of nucleic acid designed to bind to specific molecular targets, are mounted on the gold shell of the sensor. When a laser is shone on the aptamer, the molecular target absorbs the light and remits it as a characteristic spectrum. When the aptamer binds with a protein, the emitted spectrum subsequently changes. This technology could ultimately offer continuous monitoring of protein concentrations in highrisk patients and, in the process, help prevent clot-related deaths.

By deactivating a key gene in the bacteria that enable Lyme disease, tick-borne transmission might be preventable. Although tested solely in mice to date, the finding could theoretically lead to vaccine development to reduce infection risk. Researchers at the bacterial diseases branch at the U.S. Centers for Disease Control and Prevention in Fort Collins, Col., focused on the bacteria’s “bba64” gene, identified in earlier research, and genetically altered the bacteria to disable the gene. After injecting the reengineered bacteria into test mice, blacklegged ticks fed on the inoculated rodents. Meanwhile, a separate group of 15 healthy mice was exposed to the ticks, which were newly infected with the altered bacterial strain. After eight weeks of exposure to the altered bacteria-carrying ticks, only two of the mice acquired Lyme disease. The researchers then extracted the altered bacteria from the same ticks and injected it directly into healthy mice. When injected with the altered bacteria — rather than having been bitten by ticks that carried it — the healthy mice acquired Lyme disease. Researchers concluded that Lyme disease could not be transmitted via normal tick bites when the bba64 gene was rendered nonfunctional, and that this step in disease transmission warranted further post-prandial glucose excursion.

SELECTED FDA BIOLOGIC DRUG APPROVALS, MARCH 2010–MAY 2010
Action dateManufacturerDrug (trade name)IndicationAdministration
Biologics license approval
March 4CSL Behring AGimmune globulin subcutaneous (human) 20% liquid (Hizentra)Primary immunodeficiencySubcutaneous infusion
April 29Dendreonsipuleucel-T (Provenge)Asymptomatic or minimally symptomatic metastatic, castrate-resistant (hormone refractory) prostate cancerIntravenous infusion
New indication
April 16Genentecherlotinib (Tarceva)Lung cancer that remains stable after chemotherapyOral (tablets)
SELECTED FDA ACTIONS, MARCH 2010–MAY 2010
ManufacturerDrug (trade name)Type of drugIndication soughtNotes
Biologics license application
Amgendenosumab (Prolia)Fully human monoclonal antibodyReduction of fractures and other skeletal-related events in patients with advanced cancerFDA is due to decide by late July on approval of denosumab as a treatment for postmenopausal osteoporosis
Orphan drug designation
Osiris TherapeuticsProchymalMesenchymal stem cellsType 1 diabetes mellitusGranted May 4
Denials or delays
InterMunepirfenidone (Esbriet)Orally active small molecule drugIdiopathic pulmonary fibrosisFDA asked for a new clinical trial
Bristol-Myers SquibbbelataceptSelective costimulation blocker (fusion protein)Kidney transplantationFDA requested 3-year data from ongoing phase 3 trials to further evaluate long-term effects

Sources: Manufacturers’ news releases, FierceBiotech, BIO SmartBrief, wire reports, and weblogs

In the hope of curing inflammatory bowel conditions such as Crohn’s disease and ulcerative colitis, scientists are focusing on genetic mutations with the goal of moving beyond treatment to a cure. Researchers at the National Institute of Allergy and Infectious Diseases, in Bethesda, Md., are looking to fix a genetic mutation known as NOD2 that is associated with Crohn’s disease by having the body repair itself through the growth of a corrected gene created through stem cell-based therapy. Induced pluripotent stem cells, or iPS cells, are made by reengineering adult specialized cells to an earlier stage where they can reproduce again. Scientists are working on correcting the genetic defect in the iPS cells so that the new cells can become fully functional. Testing on mice is expected to begin later this year.


Articles from Biotechnology Healthcare are provided here courtesy of MediMedia, USA