Rasagiline: Long-Term Results from TEMPO Cohort, MAO-B Recovery Half-Life (MDS 2005)

Subject: Rasagiline: Long-Term Results from TEMPO Cohort, MAO-B Recovery Half-Life (MDS 2005)

Date: 4/4/2005

E-MOVE reports from the 9th International Congress of Parkinson’s Disease and Movement Disorders, New Orleans 5-8 March, 2005. Pages and abstract numbers are from Movement Disorders 2005;20(suppl 10).

1. Early treatment with rasagiline is more beneficial than delayed treatment start in the long-term management of Parkinson’s disease: A subgroup analysis
RA Hauser, MF Lew, HI Hurtig, WG Ondo, J Wojcieszek, TEMPO Extension Study Group
P251, S75

Patients receiving rasagiline early maintain a benefit on total UPDRS scores versus those receiving placebo for up to 5.5 years, according to this study.

The authors report on 177 patients completing the TEMPO trial who continue to receive open-label rasagiline at 1 mg/day for at least 4.5 years. Of these, 114 had been in the early-start group, and 63 in the delayed-start group. There were no differences between these patients in age, sex distribution, disease duration, or Hoehn and Yahr stage, but patients in the delayed-start group had lower body weight (75 vs. 80 kg) and lower total baseline UPDRS score (21.0 vs. 24.7) than those in the early-start group. There were also no differences between groups in time in the study, need for additional dopaminergic therapy, or time to commencing additional therapy.

Significant differences between groups in the change from baseline UPDRS favored early start at 6 months, 4.5 years, 5.0 years, and 5.5 years (p<0.05), but not from 1 to 4 years, or at 6 years. The mean difference over time was also significant (P=0.02).

2. Long-term efficacy of rasagiline in Parkinson’s disease
MF Lew, RA Hauser, HI Hurtig, WG Ondo, J Wojcieszek, TEMPO Extension Study Group
P250, S75

Rasagiline can be administered to PD patients for up to 6 years, according to this study.

Of 398 de novo PD patients who received rasagiline during the TEMPO trial, 360 completed, and 306 elected to continue on open-label rasagiline at 1 mg/day. Mean treatment duration was 3.5 years, with the longest treatment duration 6.5 years. Approximately 10% of patients withdrew due to adverse events. After 2 years of open-label treatment, 121 remained on monotherapy.

3. In vivo measurement of brain monoamine oxidase B (MAO-B activity after rasagiline treatment, using L-[11C]Deprenyl and positron emission tomography (PET)
N Freedman, E Mishani, Y Krausz, E Blaugrund, D Ehrlich, R Chisin
P298, S89

Brain MAO-B activity recovers slowly after rasagiline treatment, consistent with the reported half-life of 40 days for de novo synthesis of MAO-B, according to this report.

Three healthy, non-smoking volunteers received 1 mg/day rasagiline for 10 days. PET scans with L-[11C]Deprenyl were obtained before treatment, after the last dose of rasagiline, at 2-3 weeks after the last dose, and 4-6 weeks after the last dose. Uptake of L-[11C]Deprenyl is inhibited by the irreversible action of rasagiline on MAO-B.

Results showed the highest baseline uptake in the caudate, lentiform nucleus, and thalamus. Immediately after treatment, uptake in all three areas fell to approximately 40% of baseline. After 2-3 weeks, it had risen to approximately 70%, and by 4-6 weeks, to 80% of baseline.

The authors conclude, “The rate of tracer recovery was slow, and consistent with the reported 40-day half-life for de novo synthesis of MAO-B.”

All three studies were supported by Teva Pharmaceuticals