New DPT boosters approved in US
The United States Food and Drug Administration (FDA) approved on June 10 a new vaccine for a single booster immunization against pertussis (whooping cough), in combination with tetanus and diphtheria, for adolescents and adults 11 to 64 years of age. The vaccine will be marketed as Adacel by Aventis Pasteur Limited. It is the first vaccine approved as a pertussis booster for adults.
Adacel is a tetanus toxoid (T), reduced diphtheria toxoid (d) and acellular pertussis vaccine (ap), Adsorbed. Adacel contains the same components as Daptacel, a DTaP vaccine indicated for infants and children manufactured by Aventis, but the diphtheria toxoid and one of the pertussis components are in reduced quantities.
Recently, FDA approved a similar vaccine called Boostrix, manufactured by GlaxoSmithKline, for use in adolescents 10 to 18 years of age.
The ability of Adacel to protect against pertussis was assessed by comparing the antibody responses of adolescents and adults who received it with the antibody responses of infants who had received Daptacel in a clinical trial. The antibody responses of the adolescents and adults who received a single dose of Adacel were at least as good as those observed in the infants following three doses of Daptacel. For diphtheria and tetanus, the antibody responses following Adacel were comparable to those following immunization with a US licensed Td vaccine.
In clinical trials, the safety of Adacel was compared with a US- licensed Td vaccine. Among adolescent recipients of Adacel, injection-site pain and low-grade fever were observed more frequently than among those who received Td vaccine. Rates of adverse reactions were similar.
Humira eases psoriasis severity
NEW ORLEANS
Psoriasis patients receiving adalimumab (Humira) achieved significant improvement in disease activity and quality of life through 60 weeks of treatment, according to new phase-II study results released in February. The study, which assessed Humira in patients with moderate to severe chronic plaque psoriasis, showed that nearly 70 percent of patients receiving Humira 40 mg every other week experienced a 75-percent improvement in their condition at week 60.
"The findings of this study are significant, with nearly 70 percent of patients experiencing sustained improvement," said lead investigator Dr. Richard Langley of Dalhousie University in Halifax, Nova Scotia.
In the study, 67 percent of patients taking Humira 40 mg achieved at least a 75-percent reduction in disease extent and severity after 60 weeks as measured by the psoriasis area and severity index (PASI) score. Furthermore, after 60 weeks more than one-third of patients taking Humira 40 mg achieved PASI 90--a measurement that correlates to at least a 90-percent reduction in disease activity and severity score and is considered a significant skin measurement that goes beyond what is typically highlighted in clinical trials. Additionally, almost two-thirds of patients were determined to be "clear" or "almost clear" of their psoriasis as measured by the physician's global assessment.
Patients also recorded significant improvement in quality of life measures after 60 weeks of treatment, with 34.3 percent of patients reporting their quality of life was "not at all" affected by their psoriasis, as measured by the dermatology life quality index (DLQI)--a measure of patient-reported outcomes in dermatology.
"The study results are encouraging for patients whose lives continue to be negatively impacted by the effects of psoriasis," said Dr. Rebecca Hoffman, global project head for Immunology Development at Abbott. "As we move forward into Phase III development, we are optimistic about the potential of Humira in the treatment of psoriasis."
Humira is the first fully human monoclonal antibody approved in Europe for rheumatoid arthritis, and the first tumor-necrosis-factor-alpha (TNF-ALPHA) antagonist approved with an indication for use with methotrexate or as monotherapy. To date, Humira has been approved in 57 countries, including the United States, and prescribed to more than 83,000 patients suffering from RA. Clinical trials are currently underway evaluating its potential other autoimmune diseases.
Despite many available treatment options for psoriasis, some biologic treatments that target specific aspects of the immune system and help prevent the rapid growth of skin cells and formation of plaques are proving to be effective for those with moderate to severe forms of psoriasis---which accounts for approximately one-third of the 4.5 million people in the US who suffer from the disease.
Entecavir gets FDA green light
The United States Food and Drug Administration (FDA) has approved entecavir for the treatment of chronic hepatitis B infection in adults with evidence of active viral replication, persistent elevations in serum aminotransferases (ALT) or histologically active disease. Entecavir is an oral antiviral therapy designed to block the replication of hepatitis B virus (HBV) in the body by interfering with the virus's ability to infect cells.
Bristol-Myers Squibb Company, which manufactures the drug, said it is working to bring entecavir to the Asia-Pacific region, where 75 percent of the world's 400 million chronically infected hepatitis B patients live.
"With the approval of entecavir, Bristol-Myers Squibb will now be able to address another area of significant unmet medical need, building on our growing presence in fighting cancer, HIV/AIDS, schizophrenia, and other diseases," said Peter Dolan, chief executive officer. "Entecavir represents the company's fourth new pharmaceutical approved in less than two and a half years, and has the potential to help many adult patients with chronic hepatitis B infection."
"In clinical trials, entecavir demonstrated greater levels of viral suppression compared to lamivudine after 48 weeks of treatment," said Dr. Robert Gish, medical director of the California Pacific Medical Center's Liver Transplant Program.
Entecavir is a nucleoside analog with a recommended dosage of a single 0.5-milligram tablet once-daily for chronic hepatitis B patients beginning treatment for the first time (nucleoside-naïve patients), and a single one-milligram tablet once-daily for patients experiencing resistance to lamivudine (lamivudine-refractory patients).
The entecavir clinical trial program was the largest in chronic hepatitis B and the first to compare two antivirals, entecavir and lamivudine (the most commonly used oral antiviral therapy for the treatment of chronic hepatitis B worldwide). Entecavir demonstrated statistically significant improvements compared with lamivudine in liver histology, HBV viral-load reduction to undetectable levels (defined as less than 300 copies/mL), and ALT normalization.
In one of the studies (AI463-027) led by Professor Ching-Lung Lai, chief of the division of gastroenterology and hepatology at the University of Hong Kong's Department of Medicine in China, 70 percent of patients treated with entecavir for 48 weeks demonstrated histologic improvements compared with 61 percent of patients treated with lamivudine (p=0.014) using the primary efficacy endpoint defined as improvement in Knodell necroinflammatory score by at least two points plus no worsening of Knodell fibrosis. There was no significant difference between the two treatment arms in the secondary end point measure of liver histology using the Ishak Fibrosis Score analysis.
In these studies, entecavir demonstrated comparable safety to lamivudine with a favorable resistance profile. The most common side effects of entecavir in clinical studies were headache, tiredness, dizziness, and nausea.
BMS Press
Nexium improves quality of life
Treatment of gastroesophageal-reflux disease (GERD) with esomeprazole (Nexium), a proton-pump inhibitor, is associated with symptom relief and an improvement in areas of health-related quality of life, according to a new trial presented at the 2005 annual Digestive Disease Week congress (DDW) in May. The study found that reduction in symptoms after effective treatment with Nexium improved Quality of Life in Reflux and Dyspepsia (QOLRAD) scores for "well-being" by two points (based on a seven point scale).
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Prof. Ingela Wiklund of the University of Bergen, Norway and the Sahlgrenska University Hospital in Sweden and lead trial investigator of the "Feeling Thermometer" study, said that the trial clearly de-monstrates how relief from reflux has a positive effect on patients' lives. "The findings...offer further insight into the very real burden which GERD places on sufferers' lives. [They] are also key for demonstrating the importance of treating GERD with the most effective medication available...Treatment with esomeprazole made a real and measurable difference to the burden of disease these patients' suffer."
The results become more significant in the light of findings in a multinational survey, also presented at the DDW conference, that sleep disturbance leads to a substantial decline in work productivity and an increased impairment in leisure activities. The Burning Desires Survey found that among respondents who had been diagnosed with GERD, 55 percent had actually been woken up by their symptoms in the seven days prior to being questioned. Those suffering from sleep disturbance experienced a 15-percent decline in work productivity and an average of 22-percent impairment in their nonwork activities due to their GERD symptoms. With 20 to 40 percent of the adult population in western countries experiencing regular heartburn--the primary symptom of GERD--the survey demonstrates the importance of correct disease management.
Prof. Harley Liker, of the David Geffen School of Medicine, University of California, Los Angeles, said the survey results offer a real insight into the effect of GERD on patients' lives. "Our study suggests that nearly half of all people who suffer from GERD experience sleep problems which can impact their work and personal life. GERD also can be related to other health conditions, including depression and anxiety."
The survey data is supported by previous research demonstrating that, prior to treatment, employed patients experienced a 21-percent reduction in daily activities due to their GERD symptoms.
Abbott set to test ZoMaxx
Abbott Park, Illinois
Abbott has received conditional approval from the United States Food and Drug Administration for its investigational-device-exemption application for the ZoMaxx drug-eluting stent.
As a result, the company will soon begin enrolling the first 250 patients into its ZoMaxx II drug-eluting coronary stent clinical trial in the US. The trial, which will enroll 1,670 coronary artery disease patients in up to 80 centers, will compare clinical outcomes in patients treated with Abbott's ZoMaxx drug-eluting coronary stent with patients who receive Boston Scientific's Taxus Express 2.
The primary end point is nine-month ischemia-driven target vessel revascularization, a clinical measure of the need to conduct another intervention (stent, brachytherapy, or surgery) to reopen a vessel previously treated with a stent.
"Abbott is committed to develop ZoMaxx as an important new treatment for coronary-artery-disease patients worldwide," said Robert B. Hance, president of Abbott Vascular, a division of Abbott. "The ZoMaxx drug-eluting stent is poised to become an important product in Abbott Vascular's growing line of vessel closure, coronary, and endovascular products."
Abbott also continues to enroll patients in ZoMaxx I, a 400-patient prospective, randomized clinical trial being conducted in more than 30 centers in Europe, Australia, and New Zealand.
The ZoMaxx drug-eluting stent consists of three key components: a flexible stent platform called TriMaxx designed to facilitate ease of placement, a unique polymer carrier called Pharmacoat intended to enable steady drug elution, and Abbott's patent-protected immunosuppressant drug called ABT-578 that has been shown to reduce vessel renarrowing.
ABT-578 was discovered and synthesized by Abbott scientists and is the first drug designed specifically for a drug-eluting stent. Studies have shown that ABT-578 inhibits inflammation and the proliferation of smooth muscle cells that can lead to artery re-narrowing following interventional procedures.
The TriMaxx Coronary Stent has extremely thin struts (mesh scaffolding) and an ultralow crossing profile designed to facilitate stent placement in arteries. TriMaxx is the first and only stent platform developed with a tri-layer composite of stainless steel and tantalum designed to enable optimal visibility under X-ray fluoroscopy.
The application of biologically inert Pharmacoat to the ZoMaxx stent is designed to allow a steady elution of ABT-578 over time.
PRISMA shows telmisartan edge
WASHINGTON
Pfizer, the world's biggest drug maker, said it was in talks with federal regulators to revise the packaging of its popular impotence drug Viagra to mention rare instances of blindness, though officials said there was no apparent link between the medication and vision loss.
"Pfizer is in discussions with the United States Food and Drug Administration (FDA) to update the Viagra label to reflect these rare ocular occurrences," the company said.
But the FDA pointed out that there was no direct link between the drug and vision loss. "We have not determined that there is a cause-effect relationship between Viagra and NAION (nonateritic anterior ischemic optic neuropathy)," said FDA spokeswoman Susan Cruzan, noting that incidents were reported in only a "very small number of patients."
"We have reports of 38 patients on Viagra who have experienced this problem...a very small number," she said. "Viagra remains safe and effective for use if used according to the label, which does have a caution for patients who have cardiovascular disease."
She noted that NAION also occurs in men who have not taken Viagra. "These patients are probably more at risk for this condition because of other conditions like diabetes [and] high blood pressure," she said.
Pfizer likewise insisted: "There is no evidence showing that NAION occurred more frequently in men taking Viagra than men of similar age and health who did not take Viagra." The pharmaceutical firm said a review of 103 clinical trials involving some 13,000 men turned up no reports of the condition.
Pfizer noted that Viagra has been used by more than 23 million men worldwide since it went on the market seven years ago, and stressed that instances of blindness brought on by NAION are extremely rare.
According to an FDA spokeswoman cited by CBS television, which first reported on the risk, federal regulators are examining 50 cases of this type of blindness. While acknowledging that no direct links have been established between NAION and Viagra, the spokeswoman nonetheless said the FDA is "very concerned" and considers the issue a priority.
Meanwhile, US federal officials and are looking at revelation that high-risk sex offenders were getting free supplies of Viagra, with US taxpayers picking up the tab. New York State comptroller Alan Havesi said a routine audit had shown that over the past five years, 198 level-three sex offenders had received free Viagra through the government's Medicaid health service for the poor. Havesi urged "immediate action to ensure that sex offenders do not receive erectile dysfunction medication paid for by the taxpayers."
Convicted sex offenders in the US are classified according to their risk of re-offending, with level one representing the lowest risk and level three the highest.
Mary Kahn, a spokeswoman for the federal Department of Health and Human Services, said Viagra was covered by Medicaid according to a statute requiring coverage of all drugs prescribed for medically necessary purposes.
The comptroller's report triggered outrage among local New York politicians. "There is no excuse for allowing level three sex predators, the absolute worst of the worst, to have Viagra," said state assembly speaker Sheldon Silver. New York Senator Charles Schumer said it was "mind-boggling" that high-risk predators should have free access to the drug.
AFP
Dapoxetine delays the coming
WASHINGTON
If Viagra has made sex possible for men suffering from impotence, a new drug introduced in the United States aims to make it last longer. The new wonder medicine named dapoxetine, unveiled at the annual meeting of the American Urological Association, is designed to help millions of men around the world cope with premature ejaculation (PE) wreaking havoc on their sex lives.
Although much less publicized than erectile dysfunction (ED), premature ejaculation affects between 27 percent and 34 percent of males of all age groups, according to the association. By contrast, ED affects 10 to 12 percent of all men, usually in the older age group.
PE is traditionally diagnosed when sperm release occurs two minutes or less into the sexual act, or even before penetration.
"The impact premature ejaculation can have on men and their partners can be devastating for a relationship and, currently, there are no truly optimal therapies for PE," said Doctor Jon Pryor, chief urologist at the University of Minnesota and lead researcher during dapoxetine's clinical trials.
The test involved 2,614 men aged between 18 and 77, who maintained monogamous sexual relationships of more than six months and suffered from PE. Each received 30 milligrams or 60 milligrams of dapoxetine over 12 weeks in two identical placebo-controlled trials. The results showed the drug helped them lengthen intercourse three to four times.
What's more, dapoxetine increased their staying power with the first dose and helped maintain the increases over the whole study period. The percentage of study participants rating their control over ejaculation as "fair to very good" increased from 2.5 percent to nearly 52 percent for those taking 30-milligram doses of dapoxetine.
For those taking 60 milligrams, it shot up from 3.3 percent to more than 58 percent, the trials showed. The share of pill takers calling their satisfaction from intercourse "good to very good" almost doubled, as did the satisfaction of their female partners.
The most common adverse side effect reported with both doses were nausea and headache. Pryor called the results "compelling." "They demonstrate that, for the first time, a medicine can be taken by men on an on-demand basis and provide significant improvement in their PE condition," he said.
The US Food and Drug Administration is reviewing an application for the pioneer drug, which was developed by Ortho-McNeil Pharmaceutical, an affiliate of Johnson & Johnson.
AFP
Galida shows promising results
SAN DIEGO, California
New phase-II data presented at the 65th annual American Diabetes Association (ADA) scientific sessions show that tesaglitazar (Galida) is well tolerated and significantly improves glucose control and lipid abnormalities in patients with type 2 diabetes. The Glucose and Lipid Assessment in Diabetics (GLAD), a 12- week, dose-ranging study in 500 patients with type 2 diabetes, showed that treatment with Galida resulted in the following:
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Reduction in fasting plasma glucose of up to 61 mg/dL. At the 1 mg dose taken forward in phase III, a reduction of 41 mg/dL was observed.
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Reduction in fasting triglycerides (TGs) of up to 41 percent (33 percent at 1 mg).
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Significant increase (15 percent at 1 mg) in high-density lipoprotein (HDL).
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Reduction in low-density lipoprotein (LDL) up to 17 percent.
"The GLAD results demonstrate that Galida improves multiple cardiovascular risk factors in patients with type 2 diabetes. While it is still in early days, once we have phase-III data we may see potential for Galida to reduce the risk of developing both microvascular and macrovascular complications associated with atherosclerotic disease," said lead investigator Dr. Barry Goldstein of the Thomas Jefferson University in Philadelphia.
Meanwhile, the Study in Insulin Resistance (SIR) also showed that Galida significantly and dose-dependently improved postprandial glucose and lipid metabolism in nondiabetic subjects with manifestations of insulin resistance. The results showed the following:
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Reduction in fasting triglycerides of 37 percent and postprandial
triglycerides of 41 percent at the 1 mg dose.
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Increase in HDL of 16 percent at the 1 mg dose.
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A significant reduction in fasting insulin concentration, fasting plasma
glucose, and insulin resistance.
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A 40-percent reduction in free fatty acids.
Prof. Björn Fagerberg of the Sahlgrenska University Hospital in Gothenburg, Sweden, said Galida "may have the potential to prevent or delay the onset of diabetes and complications in people with metabolic syndrome."
Commented Gunnar Olsson, vice president and head of cardiovascular therapy area at AstraZeneca: "With the prevalence of type 2 diabetes and metabolic syndrome rising worldwide, we are facing a cardiovascular pandemic with devastating consequences both for individuals and health systems. A new therapy like Galida could be promising because it targets the underlying pathophysiology associated with type 2 diabetes and metabolic syndrome."
Novo Nordisk's Levemir approved
COPENHAGEN
The US Food and Drug Administration (FDA) has given the green light for the sale of Levemir, a long-acting insulin analog for the treatment of diabetes, Danish pharmaceutical maker Novo Nordisk said. The drug has already been approved in 37 countries, including the European Union member states, said the company, a world leader in diabetes care.
With the US approval of Levemir, Novo Nordisk is the only company in the US with a complete range of insulin products, including rapid-acting NovoLog and premixed NovoLog Mix. The product will now compete on the US market with Lantus, a similar drug made by French group Sanofi-Aventis.
Novo Nordisk hopes to make Levemir available to the US market in 2006, but the FDA decision will have no impact on the company's earnings for 2005, it said.
Analysts expect Levemir to generate sales of some US$123 million in 2006.
Long-acting insulin accounts for about 40 percent of insulin sales in the US. The Danish group has a US market share, in volume, of 35 percent for insulin and more than 20 percent for insulin analog.
"Despite the fact that it has been absent from the long-acting insulin market, Novo Nordisk increased its sales in North America by 46 percent in local currencies in the first quarter of 2005," spokesman Mike Rulis said.
But the group does not expect to outdo Sanofi-Aventis's Lantus on the market. Sanofi-Aventis saw its sales rise by 51.7 percent in the US in the first quarter owing to Lantus.
Requip for restless-leg syndrome
The United States Food and Drug Administration approved ropinirole HCl (Requip) tablets for the treatment of moderate-to-severe primary restless-leg syndrome (RLS) in adults. GlaxoSmithKline said Requip is the first and only FDA-approved treatment for the chronic and disruptive neurological condition that affects approximately one in ten adults in the US.
Identified in the early 1940s by neurologist Karl Ekbom, RLS is characterized by a compelling urge to move the legs and by uncomfortable or sometimes painful sensations in the legs often described as creeping-crawling, tingling, pulling, or tightening. Symptoms generally occur at rest, such as when sitting, lying or sleeping, and are temporarily relieved by movement. These symptoms can significantly disrupt a patient's sleep and daily activities.
Requip is a second-generation dopamine agonist that directly stimulates dopamine receptors in the brain. "One of the principal benefits of treatment with Requip is relief of the urge to move the legs," said Dr. William Ondo, associate professor of neurology at Baylor College of Medicine in Houston, Texas. "Requip targets what doctors believe may be an underlying cause of the disorder, which is dysfunction of a system involving dopamine."
Avandia also reduces BP
SAN DIEGO, California
New research presented at the 65th annual scientific sessions of the American Diabetes Association (ADA) on June 11 suggest that glucose-lowering rosiglitazone maleate (Avandia) may also reduce blood pressure in people with type 2 diabetes.
In one study, combination therapy with Avandia and metformin or a sulfonylurea demonstrated sustained reduction in blood pressure in people with type 2 diabetes compared with a metformin--- sulfonylurea combination. Another study showed that Avandia in combination with metformin reduced blood pressure and microalbuminuria in patients with type 2 diabetes and microalbuminuria.
"Avandia is proven to be effective in improving blood sugar control in patients with type 2 diabetes," said Dr. George Bakris, professor of preventive medicine and internal medicine at Rush University Medical Center in Chicago and lead author of one of the studies.
The first study, Twelve Months Sustained Efficacy of Rosiglitazone Combination Therapy on Ambulatory Blood Pressure in People with Type 2 Diabetes Mellitus, is a substudy of the ongoing Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial. It included 759 people with type 2 diabetes, all of whom were inadequately controlled with metformin or a sulfonylurea. Those inadequately controlled with metformin (n=379) were randomized to receive the addition of sulfonylurea or Avandia. Those inadequately controlled with a sulfonylurea (n=380) were randomized to receive the addition of metformin or Avandia.
Addition of Avandia resulted in a clinically and statistically greater mean reduction from baseline to 12 months in 24-hour ambulatory diastolic blood pressure, compared with addition of a sulfonylurea (difference -2.02 mm Hg) or metformin (difference -3.17 mm Hg).
The second study, Rosiglitazone Added to Metformin Reduces Urinary Albumin/Creatinine Ratio and Ambulatory Blood Pressure in Subjects with Microalbuminuria and Type 2 Diabetes, involved 389 rpatients andomized to the add-on treatment with Avandia or glyburide for eight additional months following a minimum of four weeks treatment with metformin.
Avandia in combination with metformin produced a statistically significant reduction in urinary albumin/creatinine ratio (UACR) from baseline (22.8 percent) compared with the group treated with glyburide and metformin (7.1 percent). Avandia and metformin also yielded a statistically greater reduction in 24-hour ambulatory systolic and diastolic blood pressure compared with glyburide and metformin (difference -3.4 mm Hg systolic and -2.5 mm Hg diastolic).
GSK Press Office
Hepsera benefits hepa B patients
Hepatitis B, which is the leading cause of liver cancer worldwide, brings with it serious complications that lead to as many as a million global deaths every year. Liver damage is observed to be more severe and rapidly progressing in chronic HB patients negative for serum hepatitis B e antigen (HBeAg), positive for anti-HBe antigens, but have persisting, clinically significant HBV replication. This particular problem proved to be fairly common in many parts of the world, and has become a "major public-health concern."
One agent that has been proved to lead to significant histologic, virologic, and biochemical improvement in patients with HBeAg-negative CHB is adefovir dipivoxil (Hepsera), a nucleotide analog. In a study published in 2003 in the New England Journal of Medicine, 185 HBeAg-negative patients were observed for 48 weeks of their being assigned to either 10-mg adefovir dipivoxil or placebo.
Headed by Dr. Stephanos Hadziyannis of the Henri Dunant Hospital in Athens, Greece, the study was a multicenter, double-blinded trial, with a patient ratio of 2:1 (viz., for every two patients on adefovir dipivoxil, one is assigned to placebo). The primary end point was histologic improvement, seen by comparing liver-biopsy specimens taken before and after the study period.
At the end of 48 weeks, 64 percent (77 of 121) of patients on the adefovir dipivoxil group registered histologic improvements (characterized as a reduction of at least two points in the Knodell necroinflammatory score and no notable worsening of fibrosis), as opposed to 33 percent (19 of 57) of patients on placebo (p < 0.001). Also, serum HBV DNA levels were lower than 400 copies per millimeter in 51 percent of patients on adefovir dipivoxil, a condition not met by any patient on placebo (p < 0.001).
Serum alanine amino-transferase levels also normalized in 72 percent of those on adefovir dipivoxil, as opposed to 29 percent of those on placebo (p < 0.001). Aside from the fact that no HBV polymerase mutations resulting from or associated with adefovir were noted, the drug's safety profile also proved to be comparable to placebo.
Hepsera is marketed in the Philippines by GlaxoSmithKline.
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