Capsule Archive end-Nov 03
- Plenaxis approved for voluntary RMP treatment of advanced prostate cancer
- FDA approves Cialis -- third oral drug to treat erectile dysfunction
- Orphan drug designation for Icatibant (JE049) to treat angioedema
- US WorldMeds to bring first non-opiate drug addiction treatment to the U.S.
- Topamax gains approvable letter for migraine prophylaxis indication
- FDA approves Advair Diskus for COPD associated with chronic bronchitis
- Vfend receives FDA approval for treatment of esophageal candidiasis
- Fosrenol shows significant serum phosphate reduction in Chinese end-stage kidney disease patients
- FDA approves Ovcon 35 as first chewable oral contraceptive tablet for women
- Lipitor shown to stop progression of plaque build-up in arteries
- Study: FDA's fast track initiative cut total drug development time by three years
- NCI, FDA announce two new initiatives as part of strategic partnership
- Most new users of higher cost COX-2s may not need drugs' gastrointestinal protection
- Tentative Approval for Taro's fluconazole tablets ANDA
- FDA approves Ovidrel ready-to-inject liquid infertility treatment
Plenaxis approved for voluntary RMP treatment of advanced prostate cancer
ROCKVILLE, MD., November 25, 2003 -- The FDA has approved the New Drug Application (NDA) that permits marketing of Plenaxis (abarelix), a drug for advanced prostate cancer for patients who have no alternative therapy.
The drug, indicated for the treatment of the symptoms of men with advanced prostate cancer who cannot take other hormone therapies and who have refused surgical castration, will be marketed under a voluntary risk management program (RMP) agreed to and administered by the sponsor that will restrict the use of Plenaxis to patients with advanced prostate cancer, who have no alternative therapy, because of an increased risk of serious, and potentially life-threatening, allergic reactions associated with its use.
About 5-10% of men with prostate cancer have the type of advanced, symptomatic disease that would make them candidates for Plenaxis. Plenaxis is a type of medicine (called a gonadotropin-releasing hormone (GnRH) antagonist) that lowers the male hormone testosterone, which is a key factor involved in most prostate cancer growth. The effectiveness of Plenaxis in lowering testosterone production in men with advanced, symptomatic prostate cancer was demonstrated in a study of 81 men.
The study showed that such patients could avoid surgical castration by undergoing at least 12 weeks of treatment. Some of the men also experienced other benefits from the use of this product, including decreased pain and relief from urinary problems. However, three of the 81 patients in the clinical trial experienced serious allergic reactions, one of which included loss of consciousness.
The FDA and the manufacturer have agreed that marketing of Plenaxis should be restricted to those patients with advanced, symptomatic prostate cancer and who do not have other treatment options because of this increased risk of serious, and potentially life-threatening, allergic reactions.
Because of the risk of low blood pressure and fainting as part of the allergic reaction to Plenaxis, patients who receive the drug are to be monitored for at least 30 minutes after receiving a dose of the drug in their health care provider's office setting. Moreover, the manufacturer will not be distributing the drug through retail pharmacies; rather, the drug will be distributed directly to physicians and hospital pharmacies enrolled in the Plenaxis RMP.
Plenaxis is administered as an injection into the muscles of the buttocks every two weeks for the first month of therapy, followed by once every four weeks thereafter. Because the drug may stop working in certain patients, doctors should perform blood tests about every two months to make sure Plenaxis is working by keeping the level of testosterone low.
The most common side effects seen in the clinical trial were hot flashes, sleep disturbances, pain, including back pain, breast enlargement or pain, and constipation.
The Plenaxis RMP that the drug's manufacturer will be implementing is designed to help ensure that patients and physicians are fully informed of the risks and benefits of Plenaxis before using it. The RMP emphasizes the need for doctors, patients and hospital pharmacists to work together to maximize the benefit of Plenaxis and minimize the risk.
As part of the program, the sponsor will only be distributing Plenaxis to physicians who attest to certain qualifications and are enrolled in Praecis' Plenaxis PLUS (Plenaxis User Safety) Program. In addition the company is establishing educational programs for physicians, patients, and hospital pharmacists about the risks and benefits of Plenaxis.
Patients will be asked to read and sign a patient information leaflet before receiving the drug. The company will also establish a system that collects and reports adverse events to FDA. Enrolled physicians should also report serious adverse events to Praecis at 1-866-753-6294 or to FDA's MedWatch Program at 1-800-FDA-1088. Finally, the company will also be conducting studies an assessments of the risk management program, including an assessment of the prescribing and actual use of Plenaxis.
Plenaxis is marketed by Praecis Pharmaceuticals Inc., Waltham, Mass.
Source: FDA Talk Paper. More information at www.fda.gov/cder/drug/infopage/plenaxis/default.htm
FDA approves Cialis -- third oral drug to treat erectile dysfunction
ROCKVILLE, MD., November 21, 2003 -- The FDA has approved Cialis (tadalafil), an oral medication to treat erectile dysfunction (ED, or impotence) in men. This is the third oral product approved for this condition. This drug is different from currently approved products for ED in that it stays in the body longer.
Cialis is now available in approximately 50 countries and has been used by more than one million men worldwide, according to the product's discoverer and marketer, Lilly ICOS LLC. The company expects to have Cialis in U.S. pharmacies by December.
Erectile dysfunction (ED) affects millions of men in the United States. Cialis acts by relaxing muscles in the penis and blood vessels, allowing increased blood flow into the penis, which produces an erection.
Cialis was evaluated in randomized, placebo-controlled trials involving more than 4,000 men with erectile dysfunction. In two of these trials, men had ED associated with diabetes mellitus or following radical prostatectomy for prostate cancer.
The drug's effectiveness was assessed using a sexual function questionnaire. In addition, patients were asked to report if they were able to achieve an erection adequate for intercourse and whether that erection was maintained to allow completion of intercourse. In all of these trials, Cialis improved patients' ability to achieve and maintain a penile erection. In other studies, sexual activity was improved in some patients at 30 minutes after taking a dose; additional studies demonstrated improvements for up to 36 hours after taking Cialis when compared to placebo.
The recommended starting dose for most patients is 10 mg taken prior to anticipated sexual activity. A higher dose of 20mg is available for patients whose response to the 10mg dose is not adequate. A lower dose (5 mg) is also available and may be necessary for patients taking other medicines or having medical conditions that may decrease the body's ability to metabolize tadalafil. Cialis should not be used more than once per day.
Cialis should not be used with nitrates (such as nitroglycerin tablets or patches) or with an alpha blocker other than Flomax 0.4mg daily (alpha blockers are medicines used to treat benign prostatic hyperplasia and high blood pressure) because the combination may significantly lower blood pressure and lead to fainting or even death in some men.
Because some drugs affect the metabolism of Cialis, patients should inform their doctors that they are taking Cialis. For example, patients taking ketoconazole or ritonoavir should not take more than a 10mg dose of Cialis once every 72 hours.
Also, in patients with moderately or severely decreased kidney function, the starting dose is 5mg taken once daily. In this group, the dose may be increased to 10mg taken once every 48 hours. In patients with mild or moderate liver impairment, the maximum dose of Cialis is 10mg.
In most patients, after taking a single dose of Cialis, some of the drug will remain in the body for more than 2 days. In those with decreased kidney function, impairment of the liver, or those taking certain medications (e.g. ketoconazole or ritonavir) tadalafil can remain in the body longer.
Cialis should not be taken by men in whom sexual activity is inadvisable because of their underlying cardiovascular status (heart condition). Patients should inform their doctor about any heart problems that they have experienced before taking Cialis.
Cialis is not recommended in patients who have suffered a heart attack or stroke within the last six months, or patients who have significantly low blood pressure, uncontrolled high blood pressure, unstable angina, severe liver impairment, or retinitis pigmentosa (an eye disorder).
The most common side effects reported in clinical trials included headache, indigestion, back pain, muscle aches, flushing, and stuffy or runny nose. Patients who get back pain and muscle aches usually get it 12 to 24 hours after taking Cialis and these usually go away by themselves within 48 hours. A small number of patients taking Cialis also reported abnormal vision.
Before taking Cialis, patients are advised to undergo a thorough medical history and physical examination to attempt to diagnose the underlying cause of the erectile dysfunction and to identify appropriate treatment.
Cialis confers no resistance to AIDS or other sexually transmitted diseases.
Cialis is manufactured for Lilly ICOS LLC by Eli Lilly and Company. To read the company's announcement, see http://newsroom.lilly.com/news/Product/2003-11-21_cialis_us_approval.html
For full prescribing information, visit www.cialis.com
Source: FDA www.fda.gov/cder/drug/infopage/cialis/default.htm
Orphan drug designation for Icatibant (JE049) to treat angioedema
BERLIN, GERMANY, November 18, 2003 -- Jerini announced that effective December 2003, the Office of Orphan Products Development of the FDA has granted orphan drug designation to Jerini's BK2 receptor antagonist Icatibant (JE049) for the treatment of angioedema. This follows the announcement by Jerini in January that the European Agency for the Evaluation of Medicinal Products (EMEA) had granted orphan drug designation to Icatibant for the same indication.
Jerini will file an Investigational New Drug Application (IND) for Icatibant in this indication with the FDA. Regulatory approvals for the IND are expected for March 2004. Jerini is currently conducting an open phase II clinical study of Icatibant in patients with hereditary angioedema (HAE) in Europe. Impressive initial results demonstrated by Icatibant will be announced shortly.
"The FDA's orphan drug designation further strengthens our angioedema program by offering important clinical development and commercialization benefits", said Jens Schneider-Mergener, Ph.D., Chief Executive Officer of Jerini.
The FDA grants orphan drug designation for products that are intended to treat rare, life-threatening diseases or chronically debilitating conditions that affect no more than 200,000 patients in the U.S. at the time of application. Further criteria include the ability of the product to provide significant patient benefit over available treatment or to fill an unmet medical need where no other treatment exists. Orphan drug designation typically means that FDA marketing review times are expedited in comparison to other drugs.
Angioedema
The most prominent form of angioedema is the hereditary form. The prevalence of hereditary angioedema (HAE) is believed to be between 1/10,000 and 1/50,000 people worldwide. Hereditary angioedema is caused by an activation of the kinin system and increased Bradykinin concentration. During an attack of angioedema, Bradykinin levels have been shown to be up to 12-fold higher than normal. HAE is characterized by acute episodic attacks of edema (swelling) in body parts, most notably the hands, feet, face, and abdomen. In the case of an attack that affects the airway passages, HAE can be life threatening. Abdominal attacks are often associated with bouts of severe pain, nausea, and vomiting caused by swelling in the intestinal wall.
Other forms of angioedema include drug-induced angioedema which is recognized as a side effect of ACE and AT2 therapy. Affected patients may be eligible for treatment.
Icatibant, a synthetic decapeptide (peptidomimetic) with a similar structure to Bradykinin (BK), is the most potent of the BK receptor antagonists reported on so far. It has virtually the same affinity to BK receptors as BK itself, and a good stability after in vivo administration. Icatibant has exhibited an excellent safety profile in over 700 subjects. It has been successfully tested in several pharmacological models where elevated BK potentially plays a significant role. With BK being one of the most important inducers of attacks of hereditary angioedema, administration of a Bradykinin antagonist such as Icatibant is expected to be of therapeutic benefit in this patient population.
At present, Icatibant also is tested in a Phase II trial to treat refractory ascites in liver cirrhosis.
Souce: Jerini AG www.jerini.com
US WorldMeds to bring first non-opiate drug addiction treatment to the U.S.
LONDON, ENGLAND and LOUISVILLE, KY., November 18, 2003 -- Britannia Pharmaceuticals Limited announced it has signed a licensing agreement with US WorldMeds, LLC to further develop and launch Britannia's non-addictive drug addiction treatment Lofexidine Hydrochloride in the United States.
Under the terms of the agreement, US WorldMeds intends to negotiate with the National Institute on Drug Abuse (NIDA), National Institutes of Health and U.S. Department of Health Services to conduct further studies aimed at bringing Lofexidine to patients in the U.S. US WorldMeds will assume all regulatory and marketing initiatives and the commercialization of the product.
Lofexidine is the only non-opiate, non-addictive treatment approved in the United Kingdom used to manage withdrawal symptoms in patients undergoing opiate detoxification. It is effective in reducing the symptoms associated with withdrawal such as chills, vomiting, sweating, stomach cramps, diarrhea, muscle pain, and runny nose and eyes. Lofexidine has been available in the United Kingdom for several years, under the brand name BritLofex. In the UK, the treatment is responsible for approximately 20,000 detoxifications per year. The drug's proven level of safety allows it to be used in an outpatient context, giving patients another option in parts of the country and world where treatment clinics are not readily available.
"We have seen the tremendous impact that BritLofex has on the lives -- and recovery -- of addicts in the UK for more than a decade and have been working to bring this treatment to the U.S. for some time," said Max Noble, Managing Director of Britannia. "We have been searching for a competent and motivated U.S. partner to take this important drug through FDA approval and are thrilled to have found exceptionally talented, knowledgeable and passionate industry experts at US WorldMeds. We have tremendous confidence in US WorldMeds' commitment and ability to bring Lofexidine to the U.S. patients who need it."
In 1996, Britannia began working with NIDA to bring the treatment to market in the U.S. As part of this work, in April 2002, a Phase III trial investigating the use of Lofexidine for the treatment of opiate withdrawal symptoms was halted due to significant evidence of efficacy in the Lofexidine treatment group as compared with a placebo group. The Data and Safety Monitoring Board (DSMB) for the trial determined that due to the overwhelming efficacy demonstrated by Lofexidine, it would be unethical, to those receiving the placebo, to continue the clinical trial.
"Lofexidine has the potential to fundamentally change the way opiate addiction is treated in the United States and we are thrilled to help turn this potential into reality," said Paul Breckinridge "Breck" Jones, CEO of US WorldMeds. "Britannia's non-narcotic, non-addictive formulation is targeted at managing the symptoms experienced by patients undergoing medically supervised opiate withdrawal. The implications of this treatment are powerful."
In addition to the studies that have tested Lofexidine's efficacy in preventing withdrawal symptoms, a pilot study conducted at Yale University tested the drug's efficacy in relapse prevention. The results of the study, which were presented at the College on Problems of Drug Dependence's annual conference in June 2003, showed that opiate addicts treated with a combination of Lofexidine and an opiate antagonist were more likely to remain opiate-free and suffer no significant adverse effects. Although the drug does not have a license for relapse prevention as yet, further studies are planned to examine increasing the scope of Lofexidine use to include use as a long-term "aid to abstinence."
Source: Britannia Pharmaceuticals
Topamax gains approvable letter for migraine prophylaxis indication
RARITAN, N.J., November 18, 2003 -- Johnson & Johnson Pharmaceutical Research & Development (J&JPRD) announced that the FDA has issued an approvable letter related to its supplemental New Drug Application for the use of Topamax (topiramate) Tablets and Topamax (topiramate capsules) Sprinkle Capsules in adults for the prophylaxis of migraine headaches.
The approvable letter provided proposed labeling as well as a request for additional analyses of safety data. The letter did not request any additional studies, and J&JPRD will respond to the agency soon. J&JPRD submitted the application for migraine prophylaxis to the FDA on December 20, 2002.
Topamax is currently indicated in the United States as adjunctive therapy for adults and children aged 2-16 with partial-onset seizures, primary generalized tonic-clonic seizures, and in patients 2 years of age and older with seizures associated with Lennox-Gastaut syndrome. Topamax is available under various brand names in more than 95 countries. It is currently approved as adjunctive treatment for a variety of seizure types and has been approved in more than 60 countries as monotherapy treatment for epilepsy. Marketing approval for Topamax for migraine prophylaxis is being sought in several countries, and regulatory approval for that use has already been granted in the Philippines, Portugal, Thailand and Mexico.
For full U.S. prescribing information, call 1-800-682-6532 or visit www.topamax.com, or www.ortho-mcneil.com
Source: J&JPRD www.jnjpharmarnd.com
FDA approves Advair Diskus for COPD associated with chronic bronchitis
RESEARCH TRIANGLE PARK, N.C., November 18, 2003 -- The FDA has approved Advair Diskus 250/50 as a new treatment for a serious lung disease that affects millions of Americans: chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis. This is the first time that a product containing both an anti- inflammatory (fluticasone propionate) and a long-acting bronchodilator (salmeterol) has been approved for this condition.
COPD, which includes chronic bronchitis and emphysema, is a complex lung disease that has several components: inflammation, bronchoconstriction and structural changes in the airways that restrict airflow into and out of the lungs. It is a debilitating and progressive condition that results in a loss of lung function.
Until now, the only medications approved for the treatment of COPD associated with chronic bronchitis have been bronchodilators. Many COPD patients with chronic bronchitis need multiple medications to help manage their condition. Advair Diskus contains two medicines which work in different ways to improve lung function -- a key goal of COPD therapy. In a clinical study, Advair Diskus 250/50 showed significantly greater improvement in lung function than the leading long-acting bronchodilator (salmeterol) used alone.
Advair Diskus 250/50 is indicated for the twice daily, maintenance treatment of airflow obstruction in patients with COPD associated with chronic bronchitis. It does not replace fast-acting inhalers used to relieve sudden symptoms of shortness of breath.
"The approval of Advair Diskus 250/50 for this condition is important news for patients and physicians," said William Bailey, MD, professor of medicine and director of the Lung Health Center at the University of Alabama- Birmingham. "There is growing recognition that COPD is a complex disease with multiple components. Advair offers a new approach, because it contains both an anti-inflammatory and a bronchodilator that work together to improve lung function."
The two medications are combined in one breath-activated inhaler called the Diskus, which contains a built-in dose counter. Advair Diskus may make treatment more convenient: patients take just one inhalation twice a day, whereas some other treatments can require up to three inhalations four times a day.
Unlike traditional aerosol inhalers, which propel medication at a high velocity, the Diskus device is breath-activated: patients use their own breath to inhale pre-measured doses of medication. Each Diskus device contains a 30-day supply of medication and has a built-in dose counter to help patients keep track of doses. In a study of patients with obstructive lung disease, the Diskus device was shown to deliver consistent and accurate doses of medication across a wide range of inhalation levels, even in patients with severely compromised lung function.
Additional important product information
In patients with major risk factors for decreased bone mineral content, such as tobacco use, advanced age, sedentary lifestyle, poor nutrition, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and corticosteroids), Advair Diskus may pose an additional risk. Patients should talk with their doctor about ways to reduce their risk. Long-term use of inhaled corticosteroids, including fluticasone propionate, a component of Advair Diskus, may increase the risk of some eye problems (cataracts or glaucoma). Regular eye examinations should be considered.
Advair Diskus 250/50 mcg twice daily is the only approved dosage for the treatment of patients who have COPD associated with chronic bronchitis. Higher doses, including Advair Diskus 500/50, are not recommended as no additional improvement in lung function was observed in clinical trials, and higher doses of inhaled corticosteroids increase the risk of systemic effects.
Source: GlaxoSmithKline
Vfend receives FDA approval for treatment of esophageal candidiasis
NEW YORK, N.Y., November 17, 2003 -- Pfizer has received FDA approval to market Vfend (voriconazole), a broad spectrum antifungal medicine, for the treatment of esophageal candidiasis.
Candida organisms are normally found on skin and mucous membranes in healthy individuals, but in persons whose immune systems are weakened or compromised by cancer chemotherapy, organ transplants or HIV/AIDS, Candida can multiply causing potentially serious infections. In immunocompromised patients, esophageal candidiasis may coat much of the surface of the mouth resulting in pain and difficulty swallowing and may ultimately progress to more serious, invasive disease.
The basis for the approval of Vfend to treat esophageal candidiasis infections was a clinical trial with immunocompromised patients conducted at study sites in 15 countries. All patients had a proven diagnosis of esophageal candidiasis and most of the patients also had additional underlying diseases, such as hematologic malignancies, chronic obstructive pulmonary disease (COPD) and AIDS.
Patients received either Vfend or fluconazole. Those treated with Vfend had success rates of 98 percent compared to 95 percent for fluconazole. Both Vfend and fluconazole had acceptable tolerability and safety. Vfend was discovered by Pfizer researchers and was developed to address the unmet medical need for more effective and better-tolerated options for patients with invasive aspergillosis and other serious fungal infections.
Initially, Vfend was approved in the U.S. for the primary treatment of acute invasive aspergillosis and salvage therapy for rare but serious fungal infections caused by the pathogens Scedosporium apiospermum and Fusarium spp. Vfend can be administered both orally and intravenously. Pfizer is continuing to study Vfend for the treatment of serious fungal infections.
In clinical trials, the most common adverse events (all causalities) were visual disturbances, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain and respiratory disorders. The treatment-related adverse events that most often led to discontinuation in clinical trials were elevated liver function tests, rash and visual disturbances.
Full prescribing information available at www.pfizer.com, or www.Vfend.com
Source: Pfizer www.pfizer.com
Fosrenol shows significant serum phosphate reduction in Chinese end-stage kidney disease patients
SAN DIEGO, CALIF., November 14, 2003 -- Shire Pharmaceuticals announced that treatment with Fosrenol (lanthanum carbonate) significantly reduced and maintained phosphate levels in a study of Chinese end-stage renal disease (ESRD) patients with hyperphosphatemia, according to data presented at the American Society of Nephrology (ASN) 36th Annual Meeting.
The 11-week study, presented by Professor Wu-Chang Yang, Taipei Veterans General Hospital, Taiwan, and his co-authors Dr. S.S. Chiang and Dr. J.B. Chen, in 61 hemodialysis patients showed that patients' serum phosphorus levels in the lanthanum carbonate group decreased to an average of 5.13 mg/dL, significantly lower than those receiving placebo (7.24 mg/dL, p < 0.001). This reduced phosphate level was well within the phosphorus range of 3.5 to 5.5 mg/dL recommended in the new Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines on Bone Metabolism and Disease in Chronic Kidney Disease.
"Data from our study demonstrates that lanthanum carbonate has the potential to reduce high phosphate levels quickly, safely and effectively to levels that comply with the new K/DOQI guidelines. These data suggest that lanthanum carbonate, when approved and available, may provide substantial clinical benefits to people on dialysis," said Prof. Wu-Chang Yang.
Sixty percent (n=18) of lanthanum carbonate-treated patients in the study had serum phosphorus levels of less than 5.6 mg/dL (the study target level), compared with only 10 percent (n=3) of patients receiving placebo. This was considered highly statistically significant, p<0.001.
At the end of the study, patients in the lanthanum carbonate group also showed significantly lower calcium x phosphate product. A high calcium x phosphate product is a measurement that has been linked to illness and death within this patient population. Specifically, at the start of the study, the lanthanum carbonate and placebo groups had average calcium x phosphate product levels of 62.33 and 58.04, respectively. At week eight, the lanthanum carbonate group's average level dropped to 48.56, well below the new K/DOQI guidelines of less than 55 mg2/dL2, the placebo group increased to 66.06, p<0.001.
During the trial, adverse events were comparable between the lanthanum carbonate and placebo groups and were typical of populations with ESRD undergoing dialysis. Further, the adverse events noted during this study were consistent with adverse event findings from previous studies with lanthanum carbonate.
Pre-clinical data supports safety
In addition to the significant phosphate reduction seen in Yang's study, pre-clinical data also presented at ASN continued to support the overall safety profile of lanthanum carbonate. According to data from ASN posters FPO651 and FPO654, lanthanum carbonate was safe and very well tolerated by a variety of animal species, including mice, rats and dogs, at plasma exposure levels substantially higher than those used in dialysis.
Additional studies examined the effects of multiple doses of lanthanum carbonate on rats, mice and dogs. In these studies, lanthanum carbonate was administered to rats (n=120) and mice (n=100) by oral gavage throughout their lifespans and to dogs (n=8) by capsule (52 weeks). No histopathological changes were seen in the brains or livers of lanthanum carbonate-treated animals, and there was no significant penetration of lanthanum carbonate into the brain. Similarly, neurobehavioral screens in mice or dogs receiving lanthanum carbonate for up to 62 weeks were normal.
Managing hyperphosphatemia
Phosphorus, an element found in nearly all foods, is absorbed from the gastrointestinal tract into the blood stream. When the kidneys fail, they no longer effectively filter out phosphates, even with the help of blood- cleansing dialysis machines. While the normal adult range for phosphorus is 2.5 to 4.5 mg/dL, the blood phosphorus levels of many patients on dialysis exceed 6.5 mg/dL. Such levels have been linked to a significantly higher illness and death risk for patients who have undergone at least one year of dialysis. Most dialysis patients, including some 243,000 Americans, develop hyperphosphatemia.
Hyperphosphatemia disrupts the delicate interplay between the body's levels of calcium, parathyroid hormone (PTH) and vitamin D. Over time, hyperphosphatemia can ultimately lead to calcification of the heart, lung and some arteries. Accumulating evidence shows that hyperphosphatemia contributes to cardiovascular disease, which accounts for almost half of all deaths among dialysis patients. In fact, studies have shown that cardiovascular mortality in dialysis patients aged 25-34 years is more than 5 times greater than that in people aged 65-74 in the general population.
Since diet restrictions alone generally cannot control phosphate levels, patients traditionally manage hyperphosphatemia with phosphate binding agents, typically calcium or sevelamer, or occasionally aluminum salts, at every meal and snack. Such binders "soak up" phosphate in the gastrointestinal tract, before it can be absorbed into the blood. Although these agents can be effective, they can cause potentially serious side effects including hypercalcemia, bone toxicity and tolerability problems.
Lanthanum carbonate (Fosrenol)
Shire received an approvable letter for lanthanum carbonate on February 28 2003, from the FDA. The company also submitted the drug for regulatory review in the European Union and Canada. Shire has an exclusive worldwide license to develop, manufacture, use and sell lanthanum carbonate under patents owned by AnorMED Inc.
Lanthanum carbonate works by binding to dietary phosphate in the stomach. Once bound, the lanthanum carbonate/phosphate complex cannot pass through the stomach lining into the blood stream and is eliminated from the body. Consequently, a patient's overall absorption of phosphate from the diet significantly decreases. Shire has conducted an extensive clinical research program for lanthanum carbonate involving more than 1,700 patients, some of whom have been treated for 36 months or more. These clinical trials demonstrate that lanthanum carbonate is an effective phosphate binder and is well tolerated in long-term use.
Source: Shire Pharmaceuticals Group www.shire.com
FDA approves Ovcon 35 as first chewable oral contraceptive tablet for women
ROCKVILLE, MD., November 14, 2003 -- The FDA has approved Ovcon 35, an oral, spearmint-flavored contraceptive tablet that can be chewed and swallowed. This new version of Ovcon 35, indicated for the prevention of pregnancy, provides one more alternative to the many types of oral contraceptives currently on the market.
Ovcon 35 contains a progestin (norethindrone) and an estrogen (ethinyl estradiol) found in products that are already marketed.
The directions for use tell women that the pill may be swallowed whole or chewed and swallowed. If the pill is chewed and then swallowed, the woman should drink a full glass (8 ounces) of liquid immediately afterwards so that the full dose of medication reaches the stomach and no residue is left in the mouth.
Ovcon 35 is available only in a 28-day regimen. Each package contains 21 round, white tablets, with norethindrone and ethinyl estradiol followed by seven reminder green (inactive) tablets to complete a 4-week-cycle.
Like other birth control pills, Ovcon 35 is effective for prevention of pregnancy when used as directed. The risks of using this product are similar to those of all birth control pills and include an increased risk of blood clots, heart attack, and stroke. The labeling also carries the warning that cigarette smoking by women, especially over age 35 increases the risk of serious cardiovascular side effects from use of combination hormonal contraceptives.
The product is manufactured by Bristol-Myers Squibb Company, and will be marketed by Warner Chilcott.
Source: FDA
Lipitor shown to stop progression of plaque build-up in
arteries
 ORLANDO, FL, November 12, 2003 -- Patients taking Pfizer's cholesterol-lowering medicine Lipitor (atorvastatin calcium) experienced a significant reduction in the progression of atherosclerosis, or hardening of the arteries, compared to patients who received Pravachol (pravastatin), according to new data presented at the annual meeting of the American Heart Association.
The Reversing Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study followed 502 patients, who were diagnosed with coronary heart disease and required cardiac catheterization, or angiograms. Patients in the 18-month study had at least one arterial vessel with 20 percent or more constriction due to plaque build up. The study compared the effectiveness of Lipitor (80 mg/day) versus Pravachol (40 mg/day) in reducing plaque build-up. Lipitor-treated patients experienced a median 0.4% reduction in total plaque volume, defined as all of the plaque present within a segment of a single artery -- while patients who received Pravachol showed a significant increase in total plaque volume (2.7% median).
"These results clearly show that aggressively lowering cholesterol levels with atorvastatin calcium stopped the progression of atherosclerosis," said Dr. Steve Nissen, Medical Director of the Cleveland Clinic Cardiovascular Coordinating Center and Principal Investigator of the REVERSAL study. "This study further demonstrates the benefits of aggressively managing cholesterol levels to reduce the risk of atherosclerosis."
Atherosclerosis, which is a leading cause of death from heart attack and stroke, occurs when there is a build-up of cholesterol-rich fatty areas called plaques in the arteries. The break-up and dispersal of these plaques can block the blood flow throughout the body, which can be fatal. It is estimated that atherosclerosis accounts for more than 75 percent of all deaths from cardiovascular disease.
"The REVERSAL results reinforce the outstanding effectiveness of Lipitor in treating patients who have high cholesterol and signs of heart disease," said Dr. Joseph Feczko, Pfizer's executive vice president of Global Research and Development and president of Worldwide Development. "These results provide important new information that will help physicians in treating the millions of patients who suffer from this devastating disease."
The average LDL-C or "bad" cholesterol levels of patients at the beginning of the study was 150 mg/dl -- while accepted guidelines call for levels of <100 mg/dl. Prior to enrollment, study participants were not taking medication to treat their high cholesterol. Additionally, patients in the study had other heart disease risk factors which may have included a history of diabetes, hypertension or a previous heart attack. Ninety-seven percent of patients taking Lipitor reached their recommended LDL cholesterol goal levels compared to 67 percent of Pravachol patients. The rates of elevated liver enzymes were low and similar in patients taking Lipitor 80 mg and Pravachol 40 mg. There were no reported cases of rare muscle problems associated with muscle breakdown.
Researchers used technology known as intravascular ultrasound, which is a three-dimensional method of imaging, to measure the total plaque volume in a cross-section of the artery wall over the length of the vessel. The total plaque volume of the patients was measured at the beginning and at the conclusion of the study.
Since the introduction of Lipitor seven years ago, its safety and effectiveness have been supported through an extensive clinical trial program, the Atorvastatin Landmark Program, with more than 400 ongoing and completed trials involving more than 80,000 patients. Lipitor is the leading cholesterol-lowering therapy in the world with more than 62 million patient years of experience.
Lipitor (atorvastatin calcium) is a prescription drug used with diet to lower cholesterol. Lipitor is not for everyone, including those with liver disease or possible liver problems, women who are nursing, pregnant, or may become pregnant. Lipitor is not indicated for the prevention of heart disease or heart attacks.
Patients who take Lipitor should tell their doctor about any unusual muscle pain or weakness. This could be a sign of serious side effects. Patients should also inform their doctor about any medications they are currently taking to avoid possible serious drug interactions. Prescribing physicians may do simple blood tests to monitor liver function before and during drug treatment. The most commonly reported side effects are gas, constipation, stomach pain and indigestion. They are usually mild and tend to go away.
For full prescribing information, call Pfizer Medical Information at 1-800-438-1985.
Source: Pfizer www.pfizer.com
Study: FDA's fast track initiative cut total drug development time by three years
BOSTON, MASS., November 14, 2003 -- The FDA's fast track program to speed new drugs to market has shaved nearly three years off the time usually required to develop a new drug and win approval, according to a recently completed analysis by the Tufts Center for the Study of Drug Development.
The study found that clinical development time for fast track drugs approved between 1998 and 2003 was, on average, 2 to 2.5 years shorter than for non-fast track drugs.
"The fast track program has had a significant public health impact by speeding access to new drugs, particularly those that treat AIDS, breast cancer, leukemia, and other diseases that afflict millions of patients and result in the loss of tens of thousands of lives every year in the U.S.," said Tufts Center Associate Director Christopher-Paul Milne.
The Tufts Center examined implementation of the fast track program since it took effect in late 1997. The fast track program aims to expedite development and approval of drugs that address unmet medical needs for serious or life-threatening conditions.
"The fast track program has clearly made a difference," Milne said. "By 1997, the FDA's five-year-old accelerated approval regulations had resulted in about 20 approvals; within its first five years the fast track program led to 200 fast track product development designations and another two dozen approvals."
In addition to generating more designations and approvals, the fast track program is being used for development programs focusing on a growing number of disease indications.
According to Milne, fast track designations for products aimed at treating diseases other than cancer and HIV/AIDS grew from more than 30 in 2001 to more than 50 in 2003.
Other key findings from the Tufts Center analysis:
- Although average approval time for fast track biologicals was shorter than that for priority or standard biologicals, longer average clinical development time resulted in a slightly longer total development time for fast track biologicals.
- Nearly 10% of fast track designations in 2003 were for diabetes and obesity, reflecting the FDA's recent emphasis on conditions that contribute significantly to health care costs and that would benefit from innovative treatments.
- As more AIDS and AIDS-related medicines became available during the late 1990s, the share of AIDS fast track designations fell by more than half between 2001 and 2003.
Source: Tufts Center http://csdd.tufts.edu
NCI, FDA announce two new initiatives as part of strategic partnership
BETHESDA, MD., November 12, 2003 -- At a Friends of Cancer Research meeting, National Cancer Institute (NCI) Director Andrew C. von Eschenbach, M.D., and Food and Drug Administration (FDA) Commissioner Mark McClellan, M.D., Ph.D, announced two new collaborative initiatives to facilitate the development and use of better cancer treatments. The initiatives include a new system for submitting investigational new drug (IND) applications electronically under the "Cancer Biomedical Informatics Grid (caBIG) project" (http://cabig.nci.nih.gov)
"In taking these important concrete steps, we are moving the NCI-FDA partnership from an idea to a working reality that will make a difference for patients," said von Eschenbach. "Our goal is to reduce the burden of cancer for all Americans through the improved development and delivery of safe, more effective therapies."
McClellan said, "We are working to get safe and effective cancer therapies to patients as quickly and inexpensively as possible. Using modern information technologies to make our processes more efficient is a key approach to achieving this goal."
Specifically, the new initiatives will:
- Link cancer researchers around the U.S. electronically to the FDA, thereby reducing the time it takes for promising new drugs to be reviewed for testing in clinical trials. It is anticipated that electronic submission of data will allow patients to benefit from earlier access to clinical trials as a result of shorter FDA processing time of IND applications, which FDA must review before new drugs may be studied in humans. FDA currently reviews IND applications in 30 days or less.
- Initiate Cancer Fellowship Training Programs aimed at developing a corps of physicians and scientists, expert in clinical research, the regulatory approval process, and translation of research breakthroughs to clinical practice.
These initiatives result from ongoing work from the two organizations' Interagency Oncology Task Force. The task force was established in May 2003 to improve the efficiency of all aspects of cancer drug development and regulatory review.
The FDA has agreed to work with NCI to develop clinical trial management software that makes it easier for cancer research groups and the FDA to work collaboratively. As a first step, NCI and FDA will work together to build tools that facilitate electronic interaction, focusing in particular on IND applications. The two organizations will work together to coordinate standards and develop tools to streamline regulatory interactions and accelerate the overall regulatory review process for new cancer drugs. These activities will become part of the NCI's cancer Biomedical Informatics Grid, in which the FDA has agreed to participate.
Under the new Fellowship Training Programs initiative, fellows will work in clinical oncology programs at NCI, where cutting-edge therapies are evaluated in patients. They will also work in the technical and regulatory review programs at the FDA, which reviews new drugs and diagnostics. As a result, fellows will bring state-of-the-art knowledge and technology to bear on the design, conduct, and review of clinical trials. These model programs will inform and harmonize all phases of cancer drug discovery, development, and regulatory review for the benefit of cancer patients.
Source: FDA/NCI
Most new users of higher cost COX-2s may not need drugs' gastrointestinal protection
ST. LOUIS, MO., November 14, 2003 -- Most patients given new prescriptions for the more expensive COX-2 anti-inflammatory drugs had no indication of being at risk for gastrointestinal events, according to a study published by The American Journal of Managed Care. COX-2 drugs provide greater protection against gastrointestinal side effects than equally effective but lower cost treatments.
Researchers at pharmacy benefit manager Express Scripts examined new users of COX-2 therapy during early 2000 at a large, Midwest preferred provider organization. They found that 65 percent did not have an indication of being at risk for gastrointestinal events and 68 percent had not tried an equally effective lower cost nonsteroidal anti-inflammatory drug (NSAID) beforehand.
"These findings suggest that opportunities exist to encourage more cost-effective prescribing," said Emily R. Cox, PhD, lead author of the study. Possible methods cited by Cox include step therapy, where a less expensive, equally effective drug is tried first, and physician education programs that encourage physicians to try lower cost options when it is appropriate to do so.
Risk factors used in the study included history of a gastrointestinal event, age 60 years or older, recent use of anticoagulant or corticosteroid agents, higher doses of COX-2 therapy and prior use of gastroprotective agents such as proton pump inhibitors and H2 blockers, which include cimetidine.
Other diagnoses such as heartburn were also included, although not established risk factors. "These additional factors were included to be as generous as possible in identifying individuals at risk for gastrointestinal events," said Cox.
Among individuals new to COX-2 therapy, only 18.8 percent met the age criterion of being at least 60 years. Increasing the age criterion to a minimum of 65 years decreased the absolute percentage meeting the criteria to 6.8 percent. In fact, the average age of study participants was 49.5 years.
"We saw COX-2 agents being used predominantly for short-term treatment of a variety of musculoskeletal conditions. Such individuals are often not at risk for gastrointestinal events, or have not tried a lower-cost alternative first," observed Cox.
Source: Express Scripts www.express-scripts.com
Tentative Approval for Taro's fluconazole tablets ANDA
HAWTHORNE, N.Y., November 12, 2003 -- Taro Pharmaceutical Industries reported that its U.S. affiliate has received tentative approval from the FDA for its Abbreviated New Drug Application (ANDA) for fluconazole tablets in four strengths: 50 mg, 100 mg, 150 mg and 200 mg. Taro's fluconazole tablets are bioequivalent to Pfizer's Diflucan tablets.
Fluconazole tablets are a prescription antifungal product used for the treatment of candidiasis (yeast infections) affecting various parts of the body, as well as for treating cryptococcal meningitis.
A tentative approval is an FDA determination that an ANDA submission currently satisfies the substantive requirements for approval, subject to the expiration of all statutorily imposed exclusivities and restrictions. Tentative approvals do not grant marketing rights; a company may only market a product upon receiving final approval for an ANDA submission.
Source: Taro Pharmaceutical Industries www.taro.com
FDA approves Ovidrel ready-to-inject liquid infertility treatment
NEW YORK, N.Y., November 11, 2003 -- The FDA has approved Ovidrel pre-filled syringe, making it the first ready-to-inject liquid version of a drug that triggers ovulation. Previously, taking Ovidrel required patients to mix the therapy on their own. Now, new syringes come pre-filled, and can be administered in a single step.
For more information about Ovidrel, visit www.seronofertility.com, or call toll-free at 1-866-LETS-TRY.
Source: Serono
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