Evithrom (human thrombin), a blood-clotting protein used to help control bleeding during surgery, has been approved by the United States Food and Drug Administration, the first since 1954 and the only product currently licensed. Evithrom is derived from human plasma obtained from carefully screened and tested donors and has undergone steps to further reduce the risk for transfusion-transmitted diseases.
Evithrom is indicated as an aid to stop oozing and minor bleeding from capillaries and small veins and when control of bleeding by standard surgical techniques is ineffective or impractical. The product is applied to the surface of bleeding tissue and may be used in conjunction with an absorbable gelatin sponge. Evithrom must not be injected into blood vessels, which would result in serious clinical complications and may even be fatal.
"The approval of Evithrom offers an important additional option for surgeons and their patients to help control surgical bleeding," said Dr. Jesse Goodman, director of the FDA center for biologics evaluation and research. "Surgeons will now be able to choose between human thrombin and thrombin derived from cattle plasma."
In a clinical trial involving several hundred subjects, Evithrom was found comparable to cattle-derived thrombin in both safety and effectiveness.
Evithrom is manufactured by Omrix Biopharmaceuticals Ltd. of Israel and will be distributed by Johnson & Johnson Wound Management, a division of New Jersey-based Ethicon Inc.
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Europe okays Avastin for NSCLC
BASEL, Switzerland
Bevacizumab (Avastin) has been approved in Europe for use in combination with platinum-based chemotherapy as first-line treatment of patients with advanced nonsmall-cell lung cancer (NSCLC).
William Burns, chief executive of Roche's pharmaceuticals division said the approval represents a "massive breakthrough" for the treatment of individuals with advanced lung cancer. "We will continue to work with European authorities to make Avastin available to as many patients with NSCLC as possible."
The approval was based on data from the pivotal phase-III trial (E4599) In the United States and the Avastin in Lung (AVAIL) phase-III trial, which both demonstrate that Avastin is effective for the treatment of patients with NSCLC in combination with platinum-based chemotherapy.
Avastin is to be used at a dose of 7.5 or 15 mg/kg in combination with platinum-based chemotherapy to treat patients with unresectable advanced, metastatic, or recurrent NSCLC other than predominantly squamous-cell histology. The broad label allows the combination of Avastin with any platinum-based chemotherapy regimens (for example, together with taxanes or gemcitabine) at the choice of the physician.
Prof. Christian Manegold of the Heidelberg University, University Medical Center Mannheim, Germany, principal investigator of the AVAIL trial, said: "Lung cancer is an extremely difficult disease to treat and Avastin has proven that it can prolong the life of patients with NSCLC. A treatment like Avastin that breaks through the one-year survival barrier is a big step forward. The European approval for Avastin means we can reassess our expectations for lung-cancer patient survival."
Results of E4599, which involved 878 patients, showed that median survival of patients treated with Avastin at a dose of 15 mg/kg every three weeks plus chemotherapy was 12.3 months vis-à-vis 10.3 months for patients treated with chemotherapy alone. Patients receiving Avastin in combination with paclitaxel and carboplatin had a 25-percent improvement in overall survival compared with patients who received chemotherapy alone. Side effects were generally manageable.
The AVAIL study involved more than 1,000 patients worldwide with previously untreated advanced NSCLC. The results showed that by adding Avastin to a cisplatin/gemcitabine regimen progression-free survival was significantly prolonged by 20 to 30 percent compared with chemotherapy alone.
Avastin, the first treatment that inhibits angiogenesis, targets a naturally occurring protein called vascular-endothelial growth factor, a key mediator of angiogenesis, thus choking off the blood supply that is essential for the growth and spread of the tumor.
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"Diluted" vaccine against bird flu
PARIS
A novel vaccine against the H5N1 bird flu could mean that far more people will be protected against the deadly disease in case of a worldwide pandemic. In clinical trials, results of which were published in The Lancet, the new drug not only required fewer scarce antigens, it also triggered a far more effective immune response.
The new drug-which combines a standard vaccine with a patented oil-in-water emulsion-produced up to six times as many antibodies capable of neutralizing the bird-flu virus as the same dose without the emulsion. Even in weaker doses the drug, produced by GlaxoSmithKline, which also funded the study, proved highly effective.
"The number of pandemic vaccine doses can be stretched 20- to 25-fold," commented virologists Suryaprakash Sambhara of the United States Centers for Disease Control and Prevention in Atlanta, and Gregory Poland of the May Vaccine Research Group in Rochester, Minnesota.
The highly pathogenic strain of influenza known as H5N1 has caused widespread outbreaks in birds-especially in Asia, Europe, and Africa-over the last decade, as well as oft-lethal infections in humans. The human body does a poor job of producing antibodies to defend itself against the virus, especially hemagglutinin H5.
In the study, researcher Geert Leroux-Roels of the Center for Vaccinology at Ghent University in Belgium gave four antigen doses ranging from 3.8 micrograms to 30 micrograms to 400 adults, aged 18 to 60, divided into eight groups of 50. Four groups received doses with the oil-water emulsion, and four groups without.
Even at the lowest dose of 3.8 micrograms, the adjuvanted drugs produced up to twice as many antibodies as the 30-microgram doses without the added solution.
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Vaccine against killer amoeba
VANCOUVER
Canadian scientists said they have made the first animal-tested vaccine against a nasty amoeba that infects 10 percent of the world population and kills 100,000 people each year. The vaccine against Entamoeba histolytica is a breakthrough, said lead scientist Kris Chadee, because currently "there are no vaccines for any parasite ... we have the first animal-tested protective vaccine."
The vaccine is sprayed into the nose-a novel, noninvasive, and very promising method-and prompts the body's immune system to arm itself against the parasite, said Chadee.
Entamoeba histolytica is the only amoeba that kills humans. It affects people with poor immune systems, causing bloody diarrhea, dehydration, and in some cases abscesses on the liver.
Chadee and his team at the University of Calgary tested their vaccine on gerbils. All those who were vaccinated remained healthy, while the unprotected animals developed abscesses, they said in their report published in Infection and Immunity.
The next step is to test the vaccine on primates. With funding from pharmaceutical companies or a foundation, "we could see clinical trials [in humans] in five years," Chadee said, adding he would like his vaccine, once its developed, to target the population most at risk-children and poor people in developing countries. "That's the problem," he said, "because the pharmaceutical industry in North America and Europe, unless there is a profit margin, tends not to pursue it ... but I'm an optimistic scientist."
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Boxed warning for glitazones
The United States Food and Drug Administration announced that manufacturers of certain drugs approved to treat type 2 diabetes have agreed to add a stronger boxed warning on the risk of heart failure. After a review of postmarketing adverse-event reports, the FDA determined that an updated label with a boxed warning on the risks of heart failure was needed for the entire thiazolidinedione class of antidiabetic drugs.
This class includes rosiglitazone (Avandia), pioglitazone (Actos) rosiglitazone and glimepiride (Avandaryl), rosiglitazone and metformin (Avandamet), and pioglitazone and glimepride (Duetact). These drugs are used in conjunction with diet and exercise to improve blood-sugar control in adults with type 2 diabetes. The FDA had asked their manufacturers, GlaxoSmithKline and Takeda, to address these concerns.
"Under the FDA's postmarketing surveillance program, we carefully monitor new safety information for marketed drugs and take appropriate action when necessary to inform patients and health-care providers of new information," said Dr. Steven Galson, director of the FDA center for drug evaluation and research.
The FDA's review of adverse-event reports found cases of significant weight gain and edema-warning signs of heart failure. In some reports, continuation of therapy has been associated with poor outcomes, including death, the FDA noted.
The strengthened warning advises health-care professionals to observe patients carefully for the signs and symptoms of heart failure, including excessive and rapid weight gain, shortness of breath, and edema after starting drug therapy.
Patients with these symptoms who then develop heart failure should receive appropriate management of the heart failure and use of the drug should be reconsidered. People who have questions should contact their health-care providers to discuss alternative treatments.
The warning also states that these drugs should not be used by people with serious or severe heart failure who have marked limits on their activity and who are comfortable only at rest or who are confined to bed or a chair.
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Cervarix trial extended to 9 years
GlaxoSmithKline (GSK) recently announced the extension of a long-term prospective clinical trial to assess the long-term efficacy, immune response, and safety of Cervarix for three more years for a total of nine years. The trial, a blinded long-term follow-up study of a subset of women who participated in the initial efficacy study and subsequent follow-up study of Cervarix, will continue to evaluate the efficacy of the cervical-cancer vaccine in preventing infection with human papillomavirus (HPV) types 16 and 18, which are most commonly associated with cervical cancer. Additionally, the study will continue to examine the long-term efficacy of Cervarix in preventing infection for other virus types, as well as examine its long-term immune response and safety profile.
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"This long-term trial demonstrates GSK's commitment to providing additional scientific knowledge about the potential of our vaccine to offer strong and sustained protection from cervical cancer, the second most common cause of cancer death among young women," said Dr. Barbara Howe, GSK vice president and director for North American vaccine development. "We are proud to extend our current study to look even further into the future with respect to our vaccine's potential to provide long-term protection."
The extended trial includes more than 400 young women initially vaccinated with Cervarix or placebo when they were 15 to 25 years of age. Results up to 5.5 years following the first dose of Cervarix were presented at the American Association for Cancer Research annual meeting in April.
GSK launched Cervarix in the Philippines in August following approval by the Bureau of Food and Drugs. Cervarix is indicated for the prevention of cervical cancer in both young and older women (10 years of age onwards). Studies have shown that Cervarix provides 100-percent protection against HPV types 16 and 18 which are responsible for over 70 per cent of cervical-cancer cases in the Asia-Pacific. It has also shown efficacy against persistent infection caused by 12 other oncogenic HPV types beyond.
Cervarix is the only cervical cancer vaccine formulated using the innovative adjuvant system called AS04, designed to enhance immune response and prolong protection against cancer-causing HPV types. In recent clinical trials, Cervarix demonstrated high levels of antibodies and 100-percent protection over 5.5 years against HPV types 16 and 18. Published data have shown that the AS04 adjuvant formulation provides a stronger and more sustained immune response compared with a traditional aluminum adjuvant alone.
In the Philippines, about 6,000 women develop cervical cancer and 4,300 die from the disease each year. With about two-thirds of cervical-cancer cases in the country diagnosed in the advanced stages when mortality is high, 56 percent of Filipino women with cervical cancer die within five years from the time of diagnosis.
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Herceptin for copositive BrCA
The European Commission recently approved the use of trastuzumab (Herceptin) in combination with an aromatase inhibitor for the treatment of postmenopausal patients with HER2-positive and hormone-receptor-positive metastatic breast cancer. The approval was based on data from the international phase-III TANDEM study which showed that adding Herceptin to hormonal therapy doubled the median progression-free survival (time patients live without their cancer progressing), from 2.4 months to 4.8 months.
"[The] approval means that for the first time a combination of targeted therapies is available for patients who suffer from a particularly aggressive form of breast cancer," said William Burns, chief executive of Roche's pharmaceuticals division. "Herceptin consistently benefits patients regardless of whether it is given in the early- or advanced-stage settings, or whether it is in combination with chemotherapy, hormonal therapy, or as a single agent."
Comprehensive reviews have suggested that approximately two thirds of breast tumors are hormone-receptor positive. Of these, up to 25 percent are also HER2-positive. TANDEM is the first randomized study to show that this specific subset of patients with "copositive" disease (both HER2- and hormone receptor-positive) are at an increased risk of relapse, making the positive results with Herceptin even more meaningful.
TANDEM was a randomized phase-III trial that evaluated Herceptin in combination with the hormonal therapy anastrozole versus anastrozole alone as first-line therapy (or second-line hormonal therapy) in postmenopausal women with advanced (metastatic) HER2-positive and hormone-receptor-positive breast cancer.
Median progression-free survival, the primary end point, was 4.8 months for patients who received the combination as against 2.4 months for those who received hormonal therapy alone (p = 0.0016). Patients in the combination arm also responded significantly better to treatment (overall response rate was 20.3 percent v. 6.8 percent; p = 0.018). There was also a positive trend in median overall survival (28.5 months v. 23.9 months; p = 0.325). This was despite the fact that in the hormonal therapy alone arm, more than half of patients (58/104) crossed over to receive Herceptin during the trial when their disease had progressed.
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Breakthrough drug v. schizophrenia
PARIS
The first new class of drugs in more than a decade for treating schizophrenia worked at least as well in a clinical trial as standard medications, a study published in Nature showed. The new treatment also reduced certain undesirable side effects.
Unlike current antipsychotic drugs, which block the uptake of dopamine, the new drug acts on a different neurotransmitter, glutamate. Imbalances in the brain of these chemicals are largely responsible for schizophrenia's disabling symptoms, which range from hallucinations and delusions to a severely impaired ability to express emotion.
Dopamine is the chemical messenger in the brain mainly involved with thinking, emotions, behavior, and perception. Until now, the only drugs able to keep the most severe symptoms in check without debilitating side effects acted on dopamine receptors.
In a double blind clinical trial, a team led by Sandeep Patil, a researcher at Eli Lilly, which funded the study, administered the new drug-known as LY2140023-to 97 patients alongside smaller groups given placebo or olanzapine, a commonly prescribed antipsychotic medication. LY2140023 matched the effectiveness of olanzapine for both "positive" symptoms such as hallucinations as well as "negative" ones, including withdrawal. As important, it avoided some of the adverse effects associated with dopamine-targeting drugs: weight gain, increases in triglycerides, periodontitis, and inflammation of the gums.
Scientists have suspected for decades that improper neurotransmission of glutamate was linked to schizophrenia, but up to now the precise mechanism was not understood.
The researchers cautioned that this was only a "proof of concept" study to see whether the drug held promise in the treatment of schizophrenia, and that more trials to test LY2140023 against other drugs and over long time periods were needed.
M AFP
Australia recalls lumiracoxib
SYDNEY
Australia's drugs watchdog said it had ordered the recall of the antiinflammatory drug lumiracoxib (Prexige) after it was linked to two deaths. The Therapeutic Goods Administration (TGA) said Australia was the first country to withdraw the drug, which is in the same class of pharmaceuticals as rofecoxib (Vioxx), withdrawn by Merck in 2004.
Lumiracoxib is produced by Switzerland-based Novartis AG, which said it had contacted health authorities in 50 countries where the drug is sold about the withdrawal.
The move followed a review of eight cases where people suffered severe liver damage after using the drug. Two of those people died and another two required liver transplants. "As a result of those case reports we have taken this straight to our drug safety committee," said Rohan Hammett, the TGA's principal medical adviser. "They recommended that it immediately be deregistered."
Lumiracoxib, a cyclooxygenase-2 inhibitor, is taken by about 60,000 people in Australia and is prescribed for osteoarthritis, postoperative pain, pain related to dental procedures, and painful menstruation. The TGA recommended that people taking lumiracoxib seek an alternative medication and have liver-function blood tests.
Novartis said it supported the decision. "Cleary, patient safety is of the utmost importance," said Nick Kurstjens, the company's chief scientific officer for Australia.
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New drug v. Parkinson's disease
DARMSTADT, Germany
The addition of safinamide 50 to 100 mg once daily to dopamine agonist significantly improves therapy for patients with early Parkinson's disease, according to a posthoc analysis of data from a phase-III trial of the drug as an add-on treatment.
"These 18-month data suggest that at a dose of 50 to 100 mg once daily safinamide may delay the time to intervention for therapeutic adjustment and provide sustained [relief] of motor symptoms when added to dopamine agonist therapy," said Prof. Anthony Schapira of the Royal Free and University College London Medical School, one of the investigators.
Intervention was defined as a need to increase the dose of dopamine agonist, add another dopamine agonist, or discontinue treatment for lack of efficacy. Analysis of the primary efficacy measure indicated that safinamide treatment delayed intervention by 93 days as measured by the median time to event (559 v. 466 days; p = 0.334, not statistically significant).
As the risk of experiencing intervention was not constant over time (hazard ratio) a posthoc analysis permitting an evaluation of events beyond the initial phase (>240 days) indicated that patients receiving safinamide at a dose of 50 to 100 mg once daily experienced a significantly lower rate of intervention compared with patients receiving dopamine agonist monotherapy (25 v. 51 percent; p = 0.049).
Meanwhile, analysis of mean change in motor symptoms as measured by the Unified Parkinson's Disease Rating Scale part III Motor Score (UPDRS III) showed that the addition of safinamide resulted in a statistically significant reduction in motor symptoms over the 18-month treatment period (p = 0.019). This was accompanied by a statistically significant improvement in quality of life as measured by the Euro quality-of-life scale.
Side effects, electrocardiogram changes, and abnormalities in vital signs were reported with similar frequency among patients who received safinamide as an add-on to dopamine and those who received dopamine agonist alone. The most frequent adverse events, not different from placebo (dopamine agonist alone), were back pain, peripheral edema, cataract, scotoma, and dizziness.
Merck Serono has exclusive worldwide rights to develop, manufacture, and commercialize safinamide in Parkinson's disease, Alzheimer's disease, and other therapeutic applications, as per the agreement signed with Newron.
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