Juvmo (tavapadon)

Tavapadon is a once-daily oral dopamine D1/D5 receptor partial agonist, evaluated in three randomized, placebo-controlled phase 3 trials with a primary endpoint at week 26. In TEMPO-1 (fixed-dose monotherapy in early Parkinson's disease), the least-squares mean change in the MDS-UPDRS Parts II and III combined score was a decrease of 9.7 points with 5 mg and 10.2 points with 15 mg against an increase of 1.8 points with placebo (treatment differences of -11.5 and -12.1 points; P < .001 for each). In TEMPO-2 (flexible-dose monotherapy, 5 to 15 mg), the score decreased by 10.3 points with tavapadon and 1.2 points with placebo (treatment difference -9.1 points; p<0.0001). In TEMPO-3 (flexible-dose adjunct to levodopa in 507 participants with motor fluctuations), daily on time without troublesome dyskinesia increased by 1.70 hours with tavapadon and 0.60 hours with placebo (treatment difference 1.1 hours; P < .001), and off time decreased by 1.88 and 0.93 hours, respectively (treatment difference -0.94 hours). A meta-analysis of the two monotherapy trials estimated a pooled improvement of 10.55 points against placebo. The prescribing information presents the monotherapy results on MDS-UPDRS Part II, which the trials analyzed as a key secondary endpoint. No trial compared tavapadon with levodopa or with another dopamine agonist.

In the pooled monotherapy trials (Study 1 and Study 2; 833 participants), the adverse reactions reported in at least 5% of participants receiving tavapadon were nausea, headache, dizziness, fatigue, dysgeusia, vomiting, dry mouth, and anxiety; adverse reactions led to discontinuation in 100 of 505 participants (20%), 85 of them during titration or dose adjustment. In the adjunct trial (Study 3), the adverse reactions reported in at least 5% were nausea, dyskinesia, dizziness, headache, hallucinations, and orthostatic hypotension, and adverse reactions led to discontinuation in 43 of 251 participants (17%). In an interim analysis of the TEMPO-4 open-label extension, adverse events were the most common reason for treatment discontinuation (136 participants, 13.7%).