Tavapadon Brings a New Kind of Dopamine Agonist to Parkinson's Care
The FDA has approved AbbVie's once-daily tavapadon, sold as Juvmo, the first selective D1/D5 receptor agonist for Parkinson's disease. Here is what the TEMPO trials showed and what the label warns about.
The dopamine agonists physicians have long prescribed for Parkinson's disease work mainly through D2 and D3 receptors, and their use may be limited by tolerability. The newest option takes a different route. AbbVie announced on Sept. 28 that the FDA has approved tavapadon tablets, sold as Juvmo, for adults with Parkinson's disease. The company describes it as the first and only selective D1/D5 receptor agonist approved for the disease.
Tavapadon is taken once daily, with or without levodopa. AbbVie said it expects the drug to be available in the United States this month. It comes as 5, 10 and 15 mg tablets, plus a titration pack with 0.25 mg and 1 mg tablets.
What the TEMPO trials showed
The approval rests on the phase 3 TEMPO program. TEMPO-1 and TEMPO-2 enrolled people with early Parkinson's disease who were not taking levodopa. In TEMPO-1, a fixed-dose trial published this year in JAMA Neurology, scores on part II of the MDS-UPDRS, which measures everyday activities such as dressing, eating and hygiene, improved by 1.6 points on 5 mg and 1.7 points on 15 mg at week 26, while the placebo group worsened by 0.9 points. Combined part II and III scores improved by 9.7 and 10.2 points against a 1.8 point worsening on placebo.
TEMPO-2, a flexible-dose trial of 5 to 15 mg published in Lancet Neurology, showed a 1.5 point improvement in part II scores against no change on placebo, and a 10.3 point improvement in combined part II and III scores against a 1.2 point improvement on placebo.
TEMPO-3 tested tavapadon as an add-on in people already on levodopa who had motor fluctuations. At week 26, daily on time without troublesome dyskinesia rose by 1.7 hours with tavapadon, compared with 0.6 hours with placebo. Daily off time fell by 1.9 hours versus 0.9 hours.
The 85 week figures come from an open-label extension, so they describe patients who stayed on the drug rather than a comparison with placebo.
AbbVie also highlighted results from TEMPO-4, the open-label extension. Among participants on tavapadon plus levodopa for 85 weeks, 93 percent (96 of 103) did not increase their levodopa dose, and among those taking tavapadon without levodopa, 94 percent (257 of 273) did not start levodopa. Because the extension was open label, those numbers have no placebo comparison.
Side effects and warnings
Most treatment-emergent adverse events in the trials were nonserious and mild or moderate, according to AbbVie. Without levodopa, the most common were nausea, headache, dizziness, fatigue, dysgeusia, vomiting, dry mouth and anxiety. With levodopa, the most common were nausea, dyskinesia, dizziness, headache, hallucinations and orthostatic hypotension.
The safety information will look familiar to anyone who has prescribed dopaminergic therapy. It warns about low blood pressure and dizziness on standing, especially after starting the drug or increasing the dose; unusual urges such as gambling, compulsive eating, compulsive shopping and increased sex drive; hallucinations; and new or worsening dyskinesia, which may signal that the dose of tavapadon or other Parkinson's medicines needs adjustment.
What it means in clinic
Most patients will start tavapadon under a neurologist. Primary care physicians will still see them, and the useful habits are the ones that apply to any dopaminergic drug: ask about dizziness on standing, ask directly about unusual urges such as gambling or compulsive shopping, and review the full medication list, as the patient information advises, because tavapadon and certain other medicines may affect each other.
Roopal Thakkar, MD, AbbVie's chief scientific officer, said in the announcement that clinicians now have "a new treatment option that targets dopamine pathways differently." How that difference plays out against existing agonists in everyday practice is a question the trials, which compared tavapadon with placebo, do not answer.
Dr. Whitfield is a family physician and practice owner who writes about independent medicine and physician leadership.
This article is for professional education and does not replace clinical judgment. Treatment decisions should be based on the individual patient and current guidelines.
