Drugs v. fibromyalgia, kidney cancer, arterial hypertension approved
The United States Food and Drug Administration (FDA) recently approved three new drugs-pregabalin (Lyrica) to treat fibromyalgia, temsirolimus (Torisel) for advanced kidney cancer, and ambrisentan (Letairis) for pulmonary arterial hypertension.
Lyrica
Lyrica, manufactured by Pfizer, is the first drug for fibromyalgia, a disorder characterized by pain, fatigue, and sleep problems. Clinical trials showed that Lyrica reduces pain and improves daily functions for some patients with fibromyalgia, but the mechanism by which it produces such an effect is unknown.
Dr. Steven Galson, director of the FDA Center for Drug Evaluation and Research said the approval "marks an important advance and provides a reason for optimism for the many patients who will receive pain relief with Lyrica." But he stressed that consumers should understand that some patients did not experience benefit in clinical trials. "We still have more progress to make for treatment of this disorder," he added.
Persons with fibromyalgia typically experience long-lasting or chronic pain, as well as muscle stiffness and tenderness. The disorder affects mostly women and typically develops in early to middle adulthood. There is no test for the diagnosis of fibromyalgia. Doctors make a diagnosis by conducting physical examinations, evaluating symptoms, and ruling out other conditions.
Two double-blind, controlled clinical trials, involving about 1,800 patients, support the approval.
The most common side effects of Lyrica are mild-to-moderate dizziness and sleepiness, blurred vision, weight gain, dry mouth, and swelling of the hands and feet. The side effects appeared to be dose-related. Lyrica can impair motor function and cause problems with concentration and attention.
Lyrica is already approved for treating partial seizures, pain following the rash of shingles and pain associated with diabetes nerve damage (diabetic neuropathy).
Torisel
Torisel was approved based on a study that showed its use prolonged survival of patients with renal-cell carcinoma. The drug is an enzyme inhibitor, a protein that regulates cell production, growth, and survival.
"We have made significant advances in the battle against kidney cancer," said Galson. "Torisel is the third drug approved for this indication in the past 18 months, and one that shows an increased time in survival for some patients."
The safety and effectiveness of Torisel were shown in a clinical trial of 626 patients divided into three groups. One group received Torisel alone, another received a comparison drug called interferon alfa, and a third received a combination of Torisel and interferon.
The group of patients who received Torisel alone showed a significant improvement in overall survival. The median overall survival was 10.9 months for patients on Torisel alone versus 7.3 months for those treated with the interferon alone. Progression-free survival (when the disease does not get worse) increased from 3.1 months on the interferon-alone arm to 5.5 months on the Torisel-alone arm. The combination of Torisel and interferon did not result in a significant increase in overall survival when compared with interferon alone.
The most common adverse reactions occurring in at least 30 percent of Torisel-treated patients were rash, fatigue, mouth sores, nausea, edema, and loss of appetite. The most common laboratory abnormalities were high blood sugar; elevated blood lipids and triglycerides; elevated liver and kidney blood tests; and low red-cell, white-cell, and platelet counts.
Torisel is manufactured by Wyeth Pharmaceuticals Inc.
Letairis
Pulmonary arterial hypertension is a rare, life-threatening condition characterized by continuous high blood pressure within the arteries of the lungs. The small arteries in the lungs become narrowed or blocked, and the heart must work harder to pump the blood through them. Over time, the overworked heart muscle may become weak and lose its ability to pump enough blood through the lungs.
"Letairis represents a valuable addition to the treatment alternatives for this orphan disease," said Dr. John Jenkins, director of the FDA office of new drugs. "Letairis is similar to an existing drug, but offers the potential for fewer drug interactions."
Letairis, a new drug not previously approved in the US, was granted a priority review by FDA. A priority review designation is intended for products that address unmet medical needs. For priority drug applications, FDA sets a target date of six months after the date of receipt for the agency to complete all aspects of a review and to take action.
The safety and effectiveness of Letairis were demonstrated in two international clinical trials involving 393 patients. Letairis significantly improved physical activity capacity compared with placebo, as shown by a six-minute walk, a standard test. Letairis also delayed the worsening of the pulmonary hypertension.
Swelling of legs and ankles, nasal congestion, sinusitis, and flushing were the most common side effects experienced by patients using Letairis.
Letairis is manufactured by Gilead Sciences Inc. Gilead acquired the US rights to ambrisentan when it acquired Myogen Inc. in 2006. GlaxoSmithKline holds rights to ambrisentan outside of the US.
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Pegasys trial for hepatitis C
BASEL, Switzerland
Roche announced the start of a large multinational trial in patients with difficult-to-cure genotype 1 hepatitis C. This international study will evaluate the effect of peginterferon alfa-2a 40KD (Pegasys) and ribavirin in hepatitis-C patients who have a high level of virus in the blood and whose body weight are heavier than average.
The trial, known as PROGRESS (Peginterferon alfa-2a and ribavirin optimized in genotype 1 high viral load patirnts to improve SVR), will examine the benefits of using a fixed-dose induction (360 mg) of Pegasys for the first 12 weeks of therapy.
"We have seen huge advances in cure rates for hepatitis C in recent years," said Dr. Rajender Reddy of the University of Pennsylvania in Philadelphia and Dr. Stephen Harrison of the Brooke Army Medical Center in San Antonio, Texas, the lead investigators for the study. "However, patients with high levels of genotype 1 virus in their blood and who are also overweight tend to respond less well to current antiviral therapy regimens. PROGRESS will determine whether induction dosing with Pegasys in combination with a higher dose of ribavirin offers these patients an improved chance of a cure."
Roche has secured approval from the European Commission for the use of Pegasys for shorter treatment duration for some genotype 1 and 4 hepatitis-C patients who demonstrated a rapid response to therapy. With the new approval, a subset of patients with genotypes 1 and 4 HCV who achieve rapid viral response can now receive a shortened, 24-week duration of treatment with Pegasys plus ribavirin. This is half the normal treatment duration.
The EU approval was based on data from two pivotal clinical trials for Pegasys plus ribavirin, which showed that among patients who achieved a rapid viral response in the first month of treatment, up to 93 percent of those with genotype 1 HCV with a low pretreatment viral load and 83 percent of patients with genotype 4 were cured following only 24 weeks of therapy-a similar cure rate with 48 weeks of therapy.
"This is excellent news for patients with hepatitis C," said Dr. Peter Ferenci, professor of gastroenterology and hepatology at the University of Vienna, Austria. "This means that patients can find out within one month of starting therapy if they have an excellent chance of being cured and can benefit from a shortened treatment duration. This is likely to encourage patients to seek treatment and motivate them to stay on therapy."
"This license change reflects Roche's commitment to finding better treatment solutions for patients with HCV by improving treatment with existing therapies and developing new medicines to treat hepatitis C," said Claire Steers, Pegasys lifecycle leader at Roche.
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Taxotere prolongs survival
Long-term results of the large TAX 327 phase-III clinical trial confirm the survival benefit of docetaxel (Taxotere)-based treatment in patients with metastatic hormone-refractory prostate cancer, Sanofi-Aventis announced. Patients who received thrice-weekly 75mg/m2 docetaxel-prednisone regimen had a median survival 19.3 months-resulting in a reduction of the risk of death by 21 percent-as against 6.3 months for those given mitoxantrone-prednisone (p = 0.005).
The survival benefit was observed regardless of age, presence or absence of pain, baseline levels of prostate-specific antigen (PSA), performance status, and quality of life measured with FACT-P at baseline.
These results were highly significant in patients with high PSA at baseline level (=115?/mL: 17.5 months v. 12.8 months, p = 0.008), absence of pain (23.0 months v. 19.8 months, p = 0.009), with good performance status (=90percent: 22.8 months v. 19.8 months, p = 0.011) and patients with impaired quality of life (FACT-P <109: 18.3 months v. 12.4 months, p = 0.002). Statistical significance of median survival was not reach regarding age, PSA <115?g/mL, presence of pain, performance status =80 percent, and quality of life with FACT-P =109.
"This update of the TAX 327 study has demonstrated statistically significant improved survival for all patients and for those without pain or with high PSA level, and confirms that thrice-weekly 75mg/m2 Taxotere plus prednisone is the first-line standard of care in patients with metastatic hormone-refractory prostate cancer," said study cochair Dr. Ian Tannock of the Princess Margaret Hospital and University of Toronto.
The results of the weekly Taxotere regimen remain comparable as when reported in 2004, with the same trend for survival.
From the initial 2004 results, the most commonly observed adverse events in patients receiving Taxotere were anemia, alopecia, fatigue, and nausea. The incidence of grade-three and -four neutropenia was 32 percent v. 22 percent, while febrile neutropenia occurred in three percent of the patients treated with Taxotere-prednisone regimen as against two percent in those treated with mitoxantrone-prednisone.
The thrice-weekly 75mg/m2 Taxotere-prednisone regimen was approved for use as a treatment for androgen independent (hormone-refractory) metastatic prostate cancer in the United States in May 2004 and in Europe in October 2004.
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Botox eases BPH symptoms
WASHINGTON
Injections of botulinum toxin A (Botox) into the prostate gland eased the symptoms of enlarged prostate in men for up to a year, according to the results of a small study. Researchers at the Chang Gung University Medical College in Taiwan and the University of Pittsburgh School of Medicine in Pennsylvania based their study on 37 men with benign prostatic hyperplasia (BPH).
All patients received a single injection of Botox into their prostate. A year into the treatment 27 patients (73 percent) experienced a 30-percent improvement in urinary-tract symptoms and quality of life, said Dr. Yao-chi Chuang, chief investigator for the Taiwanese university.
Chuang said Botox-a popular, surgery-free cosmetic treatment for wrinkles-reduces the size of the prostate gland through apoptosis, in which the prostate cells die in a programmed manner.
The treatment posed no significant side effects, such as stress urinary incontinence or erectile dysfunction, said Pittsburgh's Dr. Michael Chancellor, senior author of the study. The reduction in size of the prostate can improve urine flow and decrease residual urine left in the bladder, he said. "Our results are encouraging because they indicate that Botox could represent a simple, safe, and effective treatment for enlarged prostate that has long-term benefits," Chancellor added.
BPH is one of the most common diseases affecting men as they age. More than half of all men over the age of 60 and by age 80 develop enlarged prostates. Forty to 50 percent will develop symptoms of BPH, including more frequent urination, urinary-tract infections, the inability to completely empty the bladder, and in severe cases, eventual damage to the bladder and kidneys, the researchers said.
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Brain-cancer vaccine okayed
LONDON
Northwest Biotherapeutics said it had won approval for commercial use of the world's first vaccine against brain cancer in Switzerland. The company intends to begin making DCVax-Brain available to patients before the end of September.
Under the Swiss approval plan, Northwest is able to manufacture the vaccine in the US and make it available for the treatment of patients with brain cancer at select centers in Switzerland.
"We are delighted to be the first company to reach the market with a personalized therapeutic vaccine for brain cancers, which carry a very bleak prognosis for patients," said Alton Boynton, president and chief executive of Northwest Biotherapeutics. "Switzerland is an attractive place to begin commercialization, due to its highly respected regulatory oversight, and its growing experience with cellular therapies. We look forward to being able to bring DCVax-Brain to patients in additional countries, and to applying our DCVax technology to many other cancers." M AFP
Warning on MRI contrast agents
The United States Food and Drug Administration (FDA) has asked manufacturers to include a new boxed warning on the product labeling of all gadolinium-based contrast agents used to enhance the quality of magnetic resonance imaging (MRI).
The requested warning would state that patients with severe kidney insufficiency who receive gadolinium-based agents are at risk for developing a debilitating and potentially fatal disease known as nephrogenic systemic fibrosis (NSF). In addition, it would state that patients just before or just after liver transplantation, or those with chronic liver disease, are also at risk for developing NSF if they are experiencing kidney insufficiency of any severity.
"FDA has been carefully monitoring potential safety signals related to these contrast agents after receiving reports about the risk of this potentially life-threatening disease," said Dr. Steven Galson, director of the FDA Center for Drug Evaluation and Research. "This latest action demonstrates FDA's continuing vigilance about ensuring the safety of drug products once they enter the marketplace."
Patients with NSF develop thickening of the skin and connective tissues, inhibiting their ability to move and may result in broken bones. Other organs are at risk of thickening as well. The cause of NSF is not known and there is no consistently effective treatment for this condition.
FDA first notified health-care professionals and the public about the gadolinium-related risks for NSF in June 2006. Information on the risks was updated in December.
Gadolinium-based contrast agents are commonly used to improve the visibility of internal structures when patients undergo MRI. Reports have identified the development of NSF following single and multiple administrations of the gadolinium-based contrast agents.
The FDA said that patients should be screened for kidney problems prior to receiving any of these imaging agents. The recommended dose should not be exceeded and enough time should elapse to ensure that a dose has been eliminated from the body before the agent is used again.
There have been no reports of NSF among patients with normal kidney function or those with mild-to-moderate kidney insufficiency.
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Alopestatin prevents hair loss
TOKYO
A Japanese medical team has found that a form of antibiotic could prevent cancer patients from losing hair during chemotherapy. Dr. Toshiyuki Sakai said "alopestatin" reduced hair loss by 70 percent when used on rats also given etoposide, which is widely used to treat lung and other cancers but causes hair loss. Sakai, professor at Kyoto Prefectural University of Medicine, said his team was hoping to put the agent to practical use in the future. "I want people to know that few studies have been made on reducing side effects of anticancer drugs," he said. "This field is lagging behind (the development of cancer drugs) but is still important for patients' quality of life."
The study is still ongoing, and the chances are "low at the moment" that alopestatin will be commercialized soon. No clinical tests are yet in sight, but one possible use for humans would be to apply it to the head in the period when hair loss is most likely to occur during chemotherapy, Sakai said.
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Adolescents benefit from vaccine
PORTO, Portugal
Data presented at the 25th European Society of Pediatric Infectious Diseases (ESPID) in Porto, Portugal, showed that GlaxoSmithKline's (GSK) cervical-cancer candidate vaccine induced high immune-response levels against the cancer-causing human papillomavirus (HPV) types 16 and 18 while remaining well tolerated in adolescent girls more than 18 months after vaccination. The trial is the largest on cervical-cancer vaccination in adolescent girls to date, with 2,067 participants.
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The immune-response levels against cancer-causing HPV 16 and 18 in 10- to 14-year-old girls were significantly higher compared with those achieved among 15- to 25-year-old women in similar trials. Researchers said the high immune response is likely to result in long-term, continued protection after vaccination against HPV 16 and 18, and may provide additional protection against other cancer-causing HPV types. Long-term protection is particularly important when vaccinating adolescent girls. HPV 16 and 18 are the most prevalent cancer-causing HPV types worldwide, responsible for 70 percent of all cervical-cancer cases.
The number of withdrawals as a result of adverse events and the number of adolescent girls experiencing at least one serious adverse event over 18 months was similar to those reported in the control group, which was given Havrix, a GSK hepatitis A vaccine.
Tino Schwarz, head of the central laboratory at the Stiftung Juliusspital, Academic Teaching Hospital of the University of Wuerzburg in Germany and a lead investigator, said: "The long-term protection and tolerability of this vaccine have already been demonstrated in 15- to 25-year-old women. Now these great results confirm that these benefits can also be seen in adolescent girls on a large scale."
Clinical trials in 15- to 25-year-old women have demonstrated that the GSK cervical-cancer vaccine provides 100-percent sustained protection against precancerous lesions caused by HPV 16 and 18 over 5.5 years. Data also show preliminary evidence that the vaccine provides additional protection against precancerous lesions due to cancer-causing HPV regardless of virus type over 5.5 years. Given the high immune response in adolescents, maintained over 18 months, it is likely that these long-term benefits could also be expected in adolescent girls, the researchers said.
The GSK cervical-cancer vaccine is formulated with a new proprietary adjuvant system, AS04, which has been shown to enhance immune response compared with a similarly formulated vaccine using the conventional aluminium hydroxide adjuvant.
"GSK has undertaken an extensive clinical-development program to document the efficacy and safety of this vaccine, which has the potential to substantially reduce the worldwide disease burden related to cervical cancer," said Dr. Hugues Bogaerts, vice president of vorldwide medical affairs HPV at GSK Biologicals.
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Avastin doubles survival rate
CHICAGO
Anticancer drug bevacizumab (Avastin), used for treating lung and colon cancer, has led to the doubling of the survival rate of people affected by kidney cancer, according to a new study unveiled at the 43rd annual meeting of the American Society of Clinical Oncology in June.
The study, which surveyed 649 patients worldwide, showed that those who received Avastin had a median survival rate of 10.2 months compared with 5.4 months for others. Avastin is marketed in the United States by Genentech, a leading biotechnology company, and by Swiss firm Roche in Europe. The two companies sponsored the survey.
"We're in a very exciting time in kidney-cancer research, with a number of new targeted therapies becoming available," said Dr. Bernard Escudier, head of the immunotherapy unit at France's Gustave Roussy Institute.
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Gemzar doubles remission
WASHINGTON
A form of chemotherapy has been found to double the period of time in which people who undergo surgery for pancreatic cancer can stay in remission, according to a new study published in the Journal of the American Medical Association.
Conducted in Germany and Austria, the study involved 368 patients who had part of their pancreas removed due to cancer. The 179 patients treated with gemcitabine (Gemzar), made by Eli Lilly, had no recurrence of pancreatic cancer for a median period of 13.4 months after surgery, compared with 6.9 months for the 175 who did not take the drug.
The researchers who conducted the study funded by Eli Lilly said the results indicate that "adjuvant treatment with gemcitabine in the dose and schedule used has minimal toxicity, does not compromise quality of life and offers a good, and currently perhaps the best, chance for prolonged disease-free survival in patients undergoing resection for pancreatic cancer."
Pancreatic cancer is one of the deadliest forms of the disease, with only one in 10 patients surviving for five years after diagnosis. The cancer is often inoperable, because it spreads rapidly to other organs.
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