Invega in extended-release form
One of the challenges in the management of patients with schizophrenia is ensuring that the efficacy and safety features of a drug is maximized. But since a number of atypical antipsychotics come in immediate-release form, patients may experience significant fluctuations in peaks and troughs. Now, with the use of OROS extended-release technology in Janssen Pharmaceutica's paliperidone ER (Invega), patients can be assured that the active ingredient of the drug they are taking is consistently released over a 24-hour period, thus reducing peaks and troughs in the plasma concentrations of the drug. The OROS technology, which was developed by Alza (a Johnson and Johnson subsidiary), makes use of the advanced osmotic drug-delivery system. This includes a liquid-drug compartment (osmotic drug core), an osmotic-push compartment, a semipermeable membrane, and a drug-delivery orifice. With osmotic pressure as driving force, smooth plasma drug concentration and consistent drug plasma levels are ensured. This permits an ideal and convenient once-a-day dosing, which is a factor that may significantly improve patients' adherence to the treatment. Results from several studies proved paliperidone ER's efficacy, safety, and tolerability profiles. The extensive clinical program through which this new drug was tested and approved involved 1,700 patients who had participated in three pivotal studies in the United States and many other countries. The superiority of paliperidone ER over placebo was demonstrated in the pooled analysis of these trials. It showed significant improvements across all doses (ranging from three to 12mg) in the mean total score of the five factor scores of the Positive and Negative Syndrome Scale (PANSS), the primary tool used to measure efficacy. Such improvement in symptoms of patients on paliperidone ER was seen as early as day four. Similarly, results further demonstrated significant improvements in patient functioning compared with placebo, this time with the use of the Personal and Social Performance Scale (PSP scale), a validated, clinically rated scale that looks into four domains of behavior-socially useful activities, personal and social relations, self-care, and disturbing and aggressive behaviors. Adverse events such as extrapyramidal symptoms, weight gain, changes in lipid levels at recommended dose (six mg), as well as discontinuations due to these adverse events for all doses, were found to be comparable to placebo. Moreover, serious adverse events were found to be more evident in placebo. Schizophrenia, one of the leading mental-health problems in the world, is seen in one out of every 100 persons. Mabelle Aban
The Bureau of Food and Drugs (BFAD) on January 18 ordered Novartis Healthcare Philippines to pull the painkiller lumiracoxib (Prexige) from the market amid fears the drug could cause liver damage. A bureau advisory said it has "determined that the risks of lumiracoxib-containing medicines are greater than their benefits," citing "reports of cases from abroad concerning potential serious liver-related side effects." "Patients who are using lumiracoxib are advised to stop taking the drug and to immediately consult their physicians for information regarding their alternative treatments," the advisory added. The antiinflammatory drug is used to treat symptoms of osteoarthritis and dysmenorrhia as well as in dental and orthopedic surgery, the bureau said. "Novartis is in the process of recalling the drug from its distribution outlets," a BFAD spokesperson said, adding that the bureau had no data on the number of people using the drug in the country and there were no reports of any patients showing the same symptoms as those reported in other countries. AFP
WASHINGTON A small trial of a malaria vaccine in Mali showed promising results, according to results published in the United States. The vaccine elicited a strong immune response among 40 adults who received it, all of whom tolerated the vaccine "very well," the United States National Institute of Allergy and Infectious Diseases (NIAID) said. It was the first trial on the candidate vaccine, designed to block the malaria parasite from entering human blood cells. A second trial involving 400 Malian children aged one to six years old is now underway. Malaria is one of the deadliest diseases in Africa and in developing countries. It kills more than one million people each year, most of them children. Research for the study was led by Mahamadou Thera at the University of Bamako, Mali, with support from the NIAID, part of the US National Institutes of Health. The researchers recruited study participants in Bandiagra, a small town in northeastern Mali where malaria is prevalent. At the peak of the rainy season in August and September, people in this part of Mali typically get up to 60 malaria-transmitting mosquito bites per month, the researchers said. Volunteers received three injections, spaced one month apart, of the vaccine or a licensed rabies vaccine, as a control. At the start of the study, all volunteers had high levels of antibodies against malaria in their blood, showing they had had prior exposure to the parasite, the researchers said. Those who received the candidate vaccine showed up to a sixfold rise of vaccine-specific antibodies, while the levels of antibodies declined among those who received the rabies vaccine. AFP
BASEL, Switzerland Menveo (MenACWY-CRM), a vaccine in development by Novartis Pharma, may protect infants using a schedule beginning at two months of age against four of the most common causes of meningococcal disease. Menveo is the only meningococcal vaccine shown to generate protection against a broad range of serogroups in infants, potentially filling a large unmet medical need. New data, published in the Journal of the American Medical Association, show that Menveo was well tolerated and generated high levels of immunogenicity in infants against meningococcal serogroups A, C, W-135, and Y with a standard infant-vaccination dosing schedule. Infants have the highest rate of meningococcal disease, a potentially deadly bacterial infection. However, no currently available quadrivalent vaccine has demonstrated a strong and lasting immune response for this age group. "These important data show that this new MenACWY vaccine has the potential to protect infants as part of the routine infant-vaccine schedule, expanding the potential serogroup coverage of currently available vaccines," said study investigator Dr. Andrew Pollard, honorary consultant pediatrician at Children's Hospital in Oxford, England. "Infants have the highest rate of meningococcal disease, and to date no quadrivalent vaccine has been immunogenic in this high risk age group," said Dr. Steve Black, adjunct professor of pediatric infectious disease at Stanford University. "These new data are encouraging and offer promise that we will soon have a vaccine to protect all children against a broad range of serogroups that cause meningococcal disease." These new results build on numerous other clinical-trial findings, which support that Menveo generates a strong immune response across all age groups. Novartis plans to seek regulatory approval for Menveo in the European Union and the United States this year. "Novartis is making great progress toward our goal of protecting all age groups from all causes of meningococcal disease," said Joerg Reinhardt, Novartis chief executive for vaccines and diagnostics. A rare but potentially vaccine-preventable disease, invasive meningococcal disease is an acute, contagious and possibly fatal disease that causes sepsis and meningitis, an infection of membranes around the brain and spinal cord. Each year, approximately 500,000 cases occur around the world, causing about 50,000 deaths. Meningitis symptoms-which can include sudden onset of fever, rash, headache, and stiff neck-can progress rapidly. Even with early and appropriate treatment, patients can die, typically within 24 to 48 hours. Up to 20 percent of those who survive infection are left with life-long disability, such as deafness, neurological damage, or limb loss.
BASEL, Switzerland The combination of aliskiren and hydrochlorothiazide (Tekturna HCT) has been approved by the United States Food and Drug Administration (FDA) as a single-tablet treatment for hypertension. Tekturna, the first new type of antihypertensive in more than a decade, is a direct renin inhibitor while HCT is a diuretic. The two medicines in this single-tablet formulation work together to lower blood pressure, with clinical data showing that the combination offers greater blood-pressure reductions than either component alone. This is the first regulatory approval of a single-tablet combination therapy involving Tekturna, known as Rasilez outside the US, which has been shown to consistently lower blood pressure for 24 hours and beyond. HCT, sometimes called a "water pill," is one of the most commonly used antihypertensive. Tekturna HCT is approved for patients not controlled by either medicine alone. The approval was based on clinical trials involving more than 2,700 patients treated with Tekturna and HCT. The efficacy of Tekturna for 24 hours and beyond is important because many medicines for high blood pressure fail to work around the clock, especially during the early morning hours when blood pressure often surges. Tekturna has also been shown to maintain blood pressure reductions for up to four days after the last dose. "Current guidelines call for aggressive treatment of high blood pressure and many patients are still not controlled," said Dr. Alan Gradman of Western Pennsylvania Hospital in Pittsburgh. "Tekturna HCT offers patients an effective new treatment option with significant blood-pressure reductions and improved convenience, by combining the complementary mechanisms of action of the first direct renin inhibitor and a diuretic in one tablet." Hypertension is estimated to affect nearly one in four adults worldwide and remains uncontrolled in nearly 70 percent of patients, most of whom require two or more medicines to reach their target blood pressure. Single-tablet combinations simplify hypertension management by reducing the number of pills patients take daily. Tekturna works by targeting renin and decreasing the activity of the renin system as measured by plasma renin activity (PRA). By reducing the effects of renin, Tekturna helps blood vessels to widen so blood pressure is lowered. Diuretics work to lower blood pressure by ridding the body of unneeded water and salt, but are also known to increase PRA. "Most patients need at least two medicines to control their high blood pressure," said Dr. James Shannon, chief medical officer at Novartis Pharma AG. "The rationale for combining a diuretic, which raises plasma renin activity, with Tekturna, which counters this increase, is compelling and unique, and Novartis is very proud to introduce this innovative combination."
The European Commission recently approved the use of the first continuous erythropoiesis receptor activator (CERA), developed by Roche, in the treatment of anemia associated with chronic kidney disease (CKD). The Commission's decision followed the "positive opinion" to grant Roche marketing authorization, which had been issued by the Committee for Medicinal Products for Human Use (CHMP) in May last year. William Burns, chief executive officer of the pharma division at Roche, welcomed CERA's approval, saying that the treatment "has the potential to deliver real clinical benefits in the management of renal anemia and provide the right frequency of treatment for all CKD patients." The aim of anemia management is to safely and smoothly increase low hemoglobin (Hb) levels to a desired target range and then to maintain patients in this range to avoid health complications. CERA is involved in stimulating red-blood-cell production at the receptor level, which more closely mimics the body's physiologic processes. This is believed to be instrumental in delivering predictable and stable hemoglobin levels. CERA is the first erythropoietin-stimulating agent (ESA) approved in the EU that offers a convenient dosing schedule of once every two weeks to correct previously untreated anemia patients. CERA is also the first ESA to directly convert all patients previously treated with any ESA to once-monthly dosing. The safety and efficacy of CERA in other indications has not been established. CERA's approval is based on efficacy and safety data from the largest clinical program ever carried out for a drug treating CKD-associated anemia. This program is composed of 10 global studies that involve more than 2,700 patients from 29 countries. CERA is the only drug to have compared itself in its registration program to three ESAs: epoetin alfa, epoetin beta, and darbepoetin alfa. Two correction and four maintenance trials were conducted in the program's third phase. Almost 3,000 CKD patients-1,789 patients treated with CERA and 948 with another ESA-were included in the analysis on safety. Approximately six percent of patients treated with CERA are expected to experience adverse reactions. The most frequent reported adverse reaction was hypertension. Globally more than 500 million people have some degree of CKD. People with CKD experience a progressive deterioration in kidney function, often over a period of years, until renal replacement therapy is needed.
Data recently published in the New England Journal of Medicine confirm the efficacy of oral chemotherapy tablet capecitabine (Xeloda) as a first-line treatment for advanced stomach cancer. The publication reinforces the drug's use for this difficult-to-treat disease, enabling clinicians to prescribe capecitabine in combination with platinum-based chemotherapy. "As an oral chemotherapy, capecitabine gives patients a valuable option over the current standard of intravenous treatment," said Prof. David Cunningham, head of the gastrointestinal and lymphoma units of the Royal Marsden National Health Service Foundation Trust, London. "Capecitabine is at least as effective as intravenous treatment and reduces the time patients need to spend in the hospital, allowing them to lead more routine lives and have more personal time. It may also avoid the need for a central intravenous line with its associated inconvenience and complications," Cunningham was one of the investigators of the phase-III REAL-2 (Randomized ECF for advanced and locally advanced esophagogastric cancer) trial, final results of which were published in the NEJM on January 3. The trial evaluated oral Xeloda and oxaliplatin as alternatives to infused fluorouracil and cisplatin in the treatment of advanced gastroesophageal cancer. Results showed both regimens to be similarly effective. Overall survival was improved in the capecitabine group (11.2 months) compared with the fluorouracil group (p = 0.02). Stomach cancer is the fourth most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide, claiming 911,000 lives a year worldwide. There is a growing consensus that oral therapies should replace intravenous treatment as long as they can demonstrate at least equivalent efficacy and don't compromise tolerability. More than 80 percent of US oncologists interviewed in a survey said that their key consideration in selecting an oral chemotherapy agent was efficacy at least equivalent to intravenous alternatives. Known as a "smart pill," Xeloda is designed to be activated by an enzyme present at higher levels in cancer cells, preserving more normal, healthy cells. This results in favorable tolerability and more convenient treatment, as compared with current standard intravenous chemotherapy. Xeloda is licensed for advanced gastric cancer, advanced breast cancer, and colorectal cancer including metastatic colorectal cancer, and colon cancer following potentially curative surgery for colon cancer.
TOKYO Japanese authorities have so far not proved assertions that oseltamivir (Tamiflu) causes neurological disorders but will keep a ban on the drug for teenagers as a precaution, the health ministry said. Tamiflu is prescribed for the common flu and has been stockpiled in some countries as a front-line drug in the event of a bird-flu pandemic. But Japanese authorities voiced alarm after more than 100 people who took Tamiflu, mostly young children and teenagers, behaved abnormally. Eight died by jumping off buildings, running into traffic or other rash action. Japan, the largest importer of Tamiflu, has suspended the drug from being administered to teenagers while studying any link between the medicine and the erratic behavior. A health-ministry panel could not prove the connection by the time it reported the interim results to the government in late December, but the ministry said it would keep its precautionary ban on the drug for teenagers. "The panel will come to a conclusion after more studies," a health- ministry official said. "This report is only something transient and we should not rush to any decision right now," he added, stressing that the panel will continue to study additional cases and collect data until March. One of the working teams of the panel studied some 10,000 cases of flu patients 17 years old and younger, of whom about 80 percent had taken Tamiflu. After studying the cases provisionally, the team found the risk of erratic behavior was greater among the patients who did not take the drug than those who did, the ministry said. Specifically, 14.7 percent of the total showed some abnormal behavior including minor symptoms, such as saying something strange. Of them, only 3.2 percent acted dangerously such as jumping off buildings. Another working team said nearly 40 percent of patients who acted abnormally had not taken the drug and warned that all flu patients could show erratic behavior. An investigation last year by the United States Food and Drug Administration into the deaths in Japan concluded there was no link with Tamiflu. Roche, the manufacturer of Tamiflu, has repeatedly denied any connection between the drug and the incidents. AFP |
