Celltech hopes for drug progress

The UK's biggest biotech firm, Celltech , has said it expects to find a new partner for its biggest drug hope some time in the second quarter of 2004.

Its main investment is in CDP 870, a potential money-spinning drug for arthritis and Crohn's disease.

The announcement was made as Celltech's financial results for 2003 were posted.

The search for a new CDP 870 partner began after Pfizer returned the rheumatoid arthritis rights to Celltech last December.

The firm recorded a pre-tax, post-exceptionals, profit of £43.4m ($78.5m) after what it called a "robust financial performance".

Celltech recorded a pre-tax, pre-exceptional, profit of £52.2m, up 4% on 2002.

The figure was in line with brokers' forecasts, which had ranged from £53.6m to £54.8m.

Product sales and royalties showed a strong 12% increase to £353.3m.

Trials begin

Two rheumatoid arthritis trials are under way to assess the impact of CDP 870 on symptoms of disease.

Dr Goran Ando, chief executive of Celltech, said: "The past year has seen good performances in Celltech's commercial operations and royalty income."

He added: "During the past year we have also streamlined Celltech's operations to better support our future growth."

He said there had been "exceptional progress in our early stage pipeline" and the continued advancement of CDP 870 development in rheumatoid arthritis and Crohn's disease.

CDP 870 is an antibody fragment used to target inflammation in a number of ailments.


This is a part of article Celltech hopes for drug progress Taken from "Arava Information" Information Blog

A New Rotavirus Vaccine: RotaShield®

A New Rotavirus Vaccine: RotaShield®

from Pediatric Pharmacotherapy

Summary

The rotavirus vaccine offers the benefit of reducing the severity of rotaviral gastrointeritis in infants, with the potential to reduce the need for hospitalization and intravenous rehydration in severely affected patients. In addition, it may reduce the need for physician office visits and parental time lost from work. The true value of the vaccine, however, remains to be proven. While the adoption of this vaacine into the routine childhood immunization schedule in the United States appears likely, its benefits must be weighed against the high cost of the available product.

This is a part of article A New Rotavirus Vaccine: RotaShield® Taken from "Arava Information" Information Blog

FDA Approvals: Relenza and Eraxis

FDA Approvals: Relenza and Eraxis  CME/CE

News Author: Yael Waknine
CME Author: Yael Waknine
DisclosuresRelease Date: April 6, 2006; Valid for credit through April 6, 2007

April 6, 2006 — The US Food and Drug Administration (FDA) has approved a new indication for zanamivir oral inhalation, allowing its use for the prophylaxis of influenza in patients aged 5 years and older; and anidulafungin infusion for the treatment of candidemia and other forms of Candida infections (intraabdominal abscess and peritonitis) and esophageal candidiasis.Zanamivir for Inhalation (Relenza) to Prevent Influenza in Adults and Children

On March 29, the FDA approved a new indication for orally inhalable zanamivir (Relenza with Diskhaler, made by GlaxoSmithKline, Inc), allowing its use for the prophylaxis of influenza in patients aged 5 years and older.

The approval was based on a review of data from 4 large-scale, placebo-controlled studies. In 2 studies of postexposure prophylaxis in households with members aged older than 5 years, use of zanamivir within 1.5 days of symptom onset for treatment of the index case and its prophylactic use in other household members were equally effective for significantly reducing the spread of influenza (4.%1 vs 19.0%).

Results from the other 2 trials showed that zanamivir significantly reduced the risk of developing symptoms of influenza in adults aged 18 years and older (mean, 29 years; 86% unvaccinated) and individuals aged 12 to 94 years (mean age, 60 years) during community influenza outbreaks (56% aged older than 65 years; 67% unvaccinated; 2.0% vs 6.1% and 0.2% vs 1.4%, respectively).

According to the FDA, zanamivir has not been proven effective for influenza prophylaxis in the nursing home setting.

Zanamivir should be administered at approximately the same time each day. The recommended dose of zanamivir for household prophylaxis in patients aged 5 years and older is 10 mg (inhalation of two 5-mg blisters) once daily for 10 days, initiated within 1.5 days of symptom onset in the index case.

For the prophylaxis of influenza in a community setting, the recommended regimen for zanamivir in adults and adolescents is 10 mg daily for 28 days, initiated within 5 days of the outbreak being identified. The safety and efficacy of this regimen has not been studied beyond 28 days.

The most frequently reported adverse events related to use of zanamivir in adults and adolescents included headaches, diarrhea, nausea, vomiting, nasal irritation, bronchitis, cough, sinus infections, ear, nose, and throat infections, and dizziness. In children, ear, nose, and throat infections, vomiting, and diarrhea were most common. Less common reported events included rashes and allergic reactions, some of which were severe.

Because of the risk for potentially fatal bronchospasm, zanamivir should not be used in patients with underlying airway disease, such as chronic obstructive pulmonary disease or asthma. Zanamivir should be discontinued in patients who develop bronchospasm or demonstrate a decline in respiratory tract function; immediate treatment and hospitalization may be required.

The FDA notes that some patients without prior pulmonary disease may also have respiratory tract abnormalities from acute infection that could resemble an adverse reaction or increase patient vulnerability to such reactions.

Zanamivir is not intended as a substitute for the yearly flu vaccine, which remains the prophylactic treatment of choice as recommended by the Centers for Disease Control and Prevention's Immunization Practices Advisory Committee.

The drug was previously approved by the FDA for the treatment of uncomplicated acute illness due to influenza A and B virus in patients aged 7 years and older who have been symptomatic for no more than 2 days.Anidulafungin Infusion (Eraxis) for Candidemia and Other Candida Infections

On February 17, the FDA approved anidulafungin intravenous (IV) infusion (Eraxis, made by Pfizer, Inc) for the treatment of candidemia and other forms of Candida infections (intraabdominal abscess and peritonitis) and esophageal candidiasis.

Patients at increased risk for candidemia and systemic candidiasis include those with compromised immune systems, stem-cell and organ-transplant recipients, patients receiving chemotherapy, patients with catheters, critically ill patients in intensive care units, surgical patients, and patients receiving prolonged antibiotic therapy.

The approval was based in part on data from a double-blind, double-dummy, randomized phase 3 study (n = 245), showing that IV anidulafungin was more effective than fluconazole for successfully treating candidemia and other forms of Candida infections by the end of therapy (median duration, 14 vs 11 days; 75.6% vs 60.2%). Also, success rates remained higher in the anidulafungin group at 2- and 6-week follow-ups (64.6% vs 49.2% and 55.9% vs 44.1%, respectively).

Results of a similar study of patients with esophageal candidiasis (n = 442; 84.6% HIV+) revealed that cure-improvement rates were similar for patients treated with anidulafungin or fluconazole (97.4% vs 98.7%). However, the relapse rate at 2 weeks was higher in the anidulafungin group (53.3% vs 19.3%).

The recommended regimen for anidulafungin in the treatment of candidemia and other Candida infections is a 200-mg loading dose on day 1, followed by a 100-mg daily dose thereafter. Therapy duration should be based on clinical response; in general, antifungals should be continued for at least 14 days after the last positive culture.

Patients with esophageal candidiasis should receive a 100-mg loading dose of anidulafungin on day 1, followed by a 50-mg daily dose thereafter. Treatment should continue for a minimum of 14 days and for at least 7 days following resolution of symptoms. Because of the risk for relapse in patients with HIV infection, suppressive therapy may be considered after a course of treatment.

The FDA notes that the drug's safety and efficacy has not been determined for pediatric patients. Anidulafungin should not be administered to patients with hypersensitivity to the drug, product excipients, or other echinocandin agents.

In clinical studies, anidulafungin and fluconazole therapy were similarly well-tolerated, with comparable rates for adverse events. Adverse events most commonly reported in the anidulafungin group included hypokalemia (3.1%), diarrhea (3.1%), and increased alanine aminotransferase levels (2.3%). In the esophageal candidiasis study, headache (1.3%) and increased gamma glutamyl transpeptidase levels (1.3%) occurred most frequently.

Anidulafungin has not been linked to a risk for renal toxicity and has no clinically relevant drug-drug interactions. Furthermore, there are no requirements for dosage adjustments based on race, age, HIV status, hepatic insufficiency, or renal insufficiency.

Some cases of clinically significant hepatic abnormalities have been reported with use of anidulafungin in patients with serious underlying medical conditions. Possible histamine-mediated symptoms have also been reported infrequently, including rash, urticaria, flushing, pruritus, dyspnea, and hypotension.

http://www.fda.gov/cder/foi/label/2006/021036s008lbl.pdf

http://www.fda.gov/cder/foi/label/2006/021632s000,021948s000lbl.pdf

Pearls for Practice

The FDA has approved a new indication for zanamivir for inhalation, allowing its use for the prophylaxis of influenza in patients aged 5 years and older. It should not be used in patients with underlying airway disease because of the risk for potentially fatal bronchospasm. Zanamivir is not intended as a substitute for annual influenza vaccinations.The recommended dose of zanamivir for prophylaxis of influenza in a household setting of patients aged 5 years and older is 10 mg (inhalation of two 5-mg blisters) once daily for 10 days, initiated within 1.5 days of symptom onset in the index case. In the community setting, prophylactic therapy should be initiated within 5 days of outbreak identification; the recommended regimen for adults and adolescents is 10 mg daily for 28 days. Doses should be taken at approximately the same time each day.According to clinical study data, intravenous anidulafungin is more effective than fluconazole for successfully treating candidemia and other forms of Candida infections. In patients with esophageal candidiasis, the majority of whom were HIV+, anidulafungin was similarly effective compared with fluconazole and associated with an increased relapse rate at 2 weeks posttherapy.

Medscape Medical News 2006. ©2006 Medscape

Legal Disclaimer The material presented here does not necessarily reflect the views of Medscape or companies that support educational programming on www.medscape.com. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.
This is a part of article FDA Approvals: Relenza and Eraxis Taken from "Buy Diflucan Fluconazole" Information Blog

Caspofungin Acetate: An Antifungal Agent

Caspofungin Acetate: An Antifungal Agent

from American Journal of Health-System Pharmacy

Bioavailability and Pharmacokinetics

Stone and colleagues [26] studied the pharmacokinetics of caspofungin acetate in 12 healthy male subjects involved in three Phase I trials. In the first dose-ranging study, subjects were given single doses of caspofungin acetate ranging from 5 to 100 mg. Following a one-hour infusion, plasma levels of caspofungin acetate were found to increase proportionately as the dose increased to 100 mg. Across all dose ranges, the average plasma clearance and elimination half-life were 11 mL/min and 9 to 10 hours, respectively. An additional elimination phase and extended half-life were observed at higher doses.

The pharmacokinetics of multiple doses were evaluated in the second Phase I study that enrolled healthy male subjects (n = 5 or 6) randomized to receive daily infusions of 15, 35, and 70 mg of caspofungin acetate for 14 days.[26] All doses were infused over one hour. Between day 1 and day 14, a greater degree of drug accumulation was observed with the higher doses, such that the average accumulation was 25% at 15 mg/day, 34% at 35 mg/day, and 50% at 70 mg/day. Mean trough concentrations were 1.36 ± 0.3 mg/L on day 1 and 2.66 ± 0.55 mg/L on day 14 (Table 3).

In a third multiple-dose Phase I study, 10 subjects were given 70 mg of caspofungin acetate daily for 21 days.[26] The average accumulation was 39% on day 14 and 47% on day 21. As was the case with the previous multiple-dose study, serum levels of caspofungin acetate were consistently maintained above 1 mg/L throughout the 24-hour dosing period (Table 3).

In a single-dose study, caspofungin acetate was evaluated in 12 healthy elderly subjects (over age 64 years) and with pooled data from 12 healthy young controls (age 24 to 44 years).[27] All subjects were given a 70- mg dose of caspofungin acetate. Elderly subjects had a minimum creatinine clearance of 60 mL/min, and half of the participants were women. The geometric mean area under the curve (AUC) ratio for elderly subjects relative to young controls was 1.28. Geometric mean 24-hour concentration increased by 32%, and harmonic mean half-life lengthened by 26% in the elderly. As was the case with previous investigators,[28] no significant gender effects were observed. Although there was a modest effect of advanced age on pharmacokinetics, the authors concluded that the effect was not significant enough to warrant a dosage adjustment in elderly patients.

In a placebo-controlled Phase I study, the authors concluded that caspofungin acetate is not subject to drug interactions based on CYP3A4 inhibition.[28]

Hajdu and colleagues [29] investigated tissue penetration of caspofungin acetate in a murine model. Following intraperitoneal administration, tissue concentrations were measured as the AUC and compared with plasma concentrations. The highest concentrations were found in the following organs: liver (16 times plasma), kidneys (3 times), and large intestine (2 times). The organs with the lowest concentrations were the heart (0.3 times plasma), thigh (0.2 times), and brain (0.06 times). Caspofungin acetate distribution into red blood cells is minimal.

In vitro protein binding in animal and human sera is reported to be 80- 96%.[29,30] The exact route of elimination has not been determined, although the proposed route of elimination is hepatic, and less than 3% of the dose is eliminated unchanged in the urine.[29]

This is a part of article Caspofungin Acetate: An Antifungal Agent Taken from "Buy Diflucan Fluconazole" Information Blog

Rheumatoid Arthritis

Rheumatoid Arthritis

from ACP Medicine

Best Tests

Physical exam of jointsSwelling, warmth, tenderness, limited range of motionX-rayOften cannot detect early pathologyUseful for following disease progressionShows bone erosions at margins of the jointShows cystlike radiolucencies in larger jointsMRICan detect pannus invasion of jointsBest image for large jointsNo specific laboratory testsSerologyMild normochromic, normocytic anemia and elevated platelet count usually present; leukocyte count generally normalESR and C-reactive protein level are usually elevated in active RA and are useful in monitoring disease activity and response to therapySerum chemistry usually normal80%-85% of RA patients are seropositive for rheumatoid factor (RF), but specificity for RA is lowCCP antibodies more specific (85%-90%) but less sensitive (50%-60%) for RA than RF; could be a useful diagnostic test in some casesSynovial fluid usually straw colored and mildly turbid; rarely diagnostic

This is a part of article Rheumatoid Arthritis Taken from "Arava Information" Information Blog