Monday, March 14, 2005

ONCE-DAILY DOSING WITH AGILECT SIGNIFICANTLY IMPROVES SYMPTOMS OF PARKINSON’S DISEASE IN PATIENTS ALREADY RECEIVING LEVODOPA, LARGO STUDY SUGGESTS

Teva Pharmaceutical Industries Ltd.'s Agilect (rasagiline mesylate) significantly improves the symptoms of Parkinson's disease (PD) among patients already receiving levodopa, suggest results from the Lasting effect in Adjunct therapy with Rasagiline Given Once daily (LARGO) study.

At the start of the study, 687 patients completed a two- to four-week placebo run-in phase in which each patient's daily dose of levodopa was optimized. Subsequently, participants were randomized to receive Agilect (n=231), Novartis AG and Orion Pharma's Comtan (entacapone; n=227) or placebo (n=229) for 18 weeks.

The primary outcome measure was the change from baseline in total daily "off time," or periods during which symptoms are not adequately controlled by treatment.

Results of the intent-to-treat analysis revealed a mean decrease in daily off time of 1.8 hours for the Agilect-treated group and 1.2 hours for the Comtan-treated group compared with a 0.4-hour decrease for the placebo-treated group.

Treatment with Agilect or Comtan also led to a significant increase in total daily "on time" as compared with placebo. The authors of the study noted that this increase usually was accomplished without a corresponding increase in dyskinesias, or motor fluctuations. Increased dyskinesias often accompany treatment with levodopa and other dopaminergic drugs.

The increase in on time was paralleled by significant improvements in the Clinical Global Improvement scale, which the authors suggested supports the clinical relevance of the primary outcome.

Patients treated with Agilect or Comtan also exhibited significant improvements in measures of activities of daily living during the off state and in motor function during the on state compared with placebo-treated patients.

Additionally, measures of postural instability and gait disturbances--two symptoms of PD that often do not respond to dopaminergic therapy--significantly improved after 18 weeks of treatment among Agilect-treated patients, but not among Comtan- or placebo-treated patients.

The incidence of adverse events was comparable between the three treatment groups. Ten percent of patients receiving Agilect, 13 percent of patients receiving Comtan and 15 percent of patients receiving placebo withdrew from the study, including 7 percent, 16 percent and 11 percent, respectively, who withdrew because of adverse events.

The authors concluded that Agilect was safe and effective in this patient population. With respect to the primary endpoint, they suggested the effect of Agilect was "of similar magnitude to that seen with [Comtan]."

"The positive results seen in this trial, together with a once-daily dose that does not require titration, means that Agilect may offer patients a new treatment option for moderate to advanced PD," added Dr. Oliver Rascol, lead investigator of the LARGO trial.

Complete results of the study were published in the March 12 issue of The Lancet.

Teva submitted a New Drug Application to the Food and Drug Administration for Agilect on Sept. 5, 2003. The company is seeking indications for the drug as a monotherapy in patients with early PD and as an adjunct therapy to levodopa in patients with moderate to advanced stages of the disease.

Teva Neuroscience Inc. and Eisai Inc. will co-promote Agilect in the United States, once approved by the Food and Drug Administration, as part of a long-term strategic alliance between Teva Pharmaceutical and Eisai Co. Ltd.

Thursday, February 17, 2005

AGILECT DECREASES OFF TIME IN LEVODOPA-TREATED PATIENTS WITH PARKINSON'S DISEASE, ACCORDING TO NEW STUDY

Teva Pharmaceutical Industries Ltd.'s Agilect (rasagiline mesylate) was found to be useful in decreasing "off" (poor motor function) time and increasing "on" (better motor function) time in patients with Parkinson's disease in a recent study.

A group of 472 patients with Parkinson's disease who experienced at least 2.5 hours daily of off time despite treatment with levodopa took part in a randomized, placebo-controlled, double-blind, parallel-group study to determine the safety, tolerability and efficacy of Agilect. During the course of 26 weeks, patients received Agilect in doses of 1.0 mg/day, 0.5 mg/d or placebo.

During the treatment period, patients receiving Agilect 1.0 mg/d, 0.5 mg/d or placebo experienced a mean adjusted decrease in total daily off time from baseline of 1.85 hours (29 percent), 1.41 hours (23 percent) and 0.91 hour (15 percent), respectively. Agilect-treated patients also experienced improved scores on an investigator-rated clinical global impression scale and the Unified Parkinson's Disease Rating Scale (UPDRS).

Patients receiving Agilect reported similar adverse events as compared with the placebo-treated group, though 18 percent of patients receiving Agilect reported an increased instance of dyskinesias compared with 10 percent of the placebo-treated group. Furthermore, patients receiving Agilect 1.0 mg/d experienced more dyskinesias than those receiving Agilect 0.5 mg/d, suggesting that benefits obtained through a higher dosage may be partially offset by increased dyskinesias, the study's authors said.

Additionally, Agilect could be shown to have protective effects associated with long-term use, as patients randomized to receive treatment for 12 months had better UPDRS scores than those randomized to delay treatment for six months. The authors said further studies are needed to explore this possibility.

The results of the trial, known as the PRESTO (Parkinson's Rasagiline: Efficacy and Safety in the Treatment of "Off"), appear in the February issue of Archives of Neurology.

Teva filed a New Drug Application for Agilect in September 2003 for the treatment of Parkinson's disease.

Monday, September 13, 2004

MAOBIS REDUCE DISABILITY, NEED FOR LEVODOPA IN PARKINSON'S PATIENTS; SUBSTANTIAL SIDE EFFECTS, INCREASED MORTALITY NOT OBSERVED

In a study of Parkinson's disease patients that examined the benefits and risks of monoamine oxidase type B inhibitors--such as selegiline, which is marketed as Eldepryl by Somerset Pharmaceuticals Inc.--researchers found that MAOBIs reduce disability, the need for levodopa and the incidence of motor fluctuations, all without substantial side effects or increased mortality.

In an effort to clarify the role of MAOBIs, researchers analyzed data from 17 trials that compared MAOBIs with placebo or levodopa.

As compared with patients taking placebo, those randomized to MAOBIs had significantly better total scores, motor scores and activities-of-daily-living scores on the unified Parkinson's disease rating scale at three months. The likelihood of requiring additional levodopa also was decreased by approximately 43 percent among patients on an MAOBI. Patients randomized to MAOBIs also were significantly less likely to develop motor fluctuations.

The groups did not significantly differ with respect to side effects or mortality.

"Our review provides no evidence that mortality is increased by selegiline and suggests that this inexpensive drug could be one of the most clinically effective and cost-effective treatments available for early Parkinson's disease," the investigators concluded.

The study was published in the Sept. 11 issue of the British Medical Journal.

In July, Teva Pharmaceutical Industries Ltd. received an approvable letter from the Food and Drug Administration for once-daily Agilect (rasagiline mesylate)--also an MAOBI--which is intended as an initial monotherapy in early Parkinson's disease treatment and as an adjunct therapy to levodopa in moderate to advanced stages of the disease.

Wednesday, July 7, 2004

TEVA RECEIVES APPROVABLE LETTER FROM FDA FOR AGILECT PARKINSON'S DISEASE THERAPY

Teva Pharmaceutical Industries Ltd. received an approvable letter from the Food and Drug Administration for once-daily health care brand name drug Agilect (rasagiline mesylate), which is intended as an initial monotherapy in early Parkinson's disease treatment and as an adjunct therapy to levodopa in moderate to advanced stages of the disease.

The company said it plans to work closely with the FDA to complete the process of receiving final approval as soon as possible.

If approved, Agilect will be co-promoted by Teva Neuroscience Inc. and Eisai Inc. in the United States. Teva and H. Lundbeck A/S will co-promote the therapy in Europe should it receive approval there.

"We are very pleased to receive this approvable letter, which is a major regulatory milestone in the approval process of Agilect," said Israel Makov, Teva's chief executive. "Today represents another important step towards Teva being able to offer a new pharmaceutical brand to the many patients who currently suffer from Parkinson's disease in the United States."