A new Parkinson's pill acts on the cells that receive dopamine

In Short. Parkinson's disease slowly destroys the brain cells that make dopamine, the chemical that helps movement start. A newly approved pill leaves those cells alone and instead switches on the cells that dopamine would normally reach. In trials it eased movement symptoms much more than a dummy pill, but no trial shows that it slows the disease.

PARKINSON'S DISEASE has two layers. The underlying problem is the death of nerve cells that make dopamine, along with clumps of a protein called alpha-synuclein, known as Lewy bodies, inside nerve cells. The symptoms are what patients notice, which are slowness, stiffness and tremor. Those follow the shortfall of dopamine. So a medicine can treat the shortfall and ease movement while the disease itself keeps progressing.

Dopamine works as a message. The cells that make it send it to cells in the striatum, a brain region that helps control movement. Parkinson's kills the senders. The receivers are still there, and each carries receptors, proteins on its surface that dopamine attaches to and so switches on. A drug that binds a receptor and switches it on, with no dopamine needed, is a receptor agonist. Some do it only part of the way, and that is a partial agonist. Receptors come in families. In reviews of the brain's movement circuits, D1-type receptors (D1 and D5) sit mostly on cells in a pathway that promotes movement, and D2-type receptors (D2 and D3) sit mostly on cells in a pathway that acts as a brake. With less dopamine, the first pathway does less and the brake does more.

The drug is tavapadon, which AbbVie said on September 28 the Food and Drug Administration (FDA) had approved, to be sold as Juvmo. Its label calls it a selective partial agonist at D1 and D5. A 2024 review, three of whose six authors were Cerevel employees (now part of AbbVie), reports lab results that it reached 65% and 81% of dopamine's own activity at D1 and D5, with little to no activity at D2 and D3. The review cites unpublished data for this.

Why build it this way? Levodopa, the main treatment, is turned into dopamine in the brain. But it is short-lived, so it is taken several times a day, and raising the dose can bring on dyskinesia, involuntary movements. Older receptor agonists such as pramipexole act mostly on D2 and D3, and pramipexole's label warns of falling asleep without warning, compulsive urges such as gambling, and hallucinations. The bet is that steadier D1 and D5 stimulation, from one pill a day, gives benefit with fewer of these problems. Tavapadon's label still warns of urges and hallucinations. In its trials, hallucinations were reported by 3% on the drug and none on placebo in early disease, and by 7% and 1% with levodopa. The label has no warning about sudden sleep, but the trials behind the approval compared it with a dummy pill, not with pramipexole, so the bet has not been tested head to head there.

The evidence comes from late-stage (phase 3) trials called TEMPO. In TEMPO-2, 304 people with early Parkinson's were randomized (assigned by chance) to tavapadon or a dummy pill, a placebo, and neither patients nor doctors knew which. Such a trial is placebo-controlled and double-blind. The main result the trial was built to measure, its primary endpoint, was the change by week 26 in the MDS-UPDRS (parts II and III combined), a clinician-rated score of daily-living and movement ability. Lower is better. The score improved, meaning it fell, by 10.3 points on tavapadon and 1.2 on placebo. More people left the drug group, 38% against 15%, most often over side effects. The FDA label, which counts the daily-living part of the score alone, shows tavapadon improving by 1.5 points and placebo by none.

TEMPO-3 tested it as an adjunct, an add-on to levodopa, in 507 people whose levodopa had begun to wear off. Its primary endpoint was "on" time, the hours when medicine is working and movement is good, without troublesome dyskinesia. By week 26 that time had risen by 1.7 hours a day on tavapadon and 0.6 on placebo, though dyskinesia was reported by 10% on the drug and 2% on placebo. Some patients then joined an open-label extension, TEMPO-4, where everyone knew they were taking the drug and there was no placebo group. Longer follow-up helps, but it is weaker evidence.

What the trials settle is symptom control, and against a dummy pill the gain was large. They do not show that tavapadon slows Parkinson's, and the label does not claim it. The Lewy body question stays open, and no approved drug has been shown to answer it. For patients, this is one more way to treat symptoms, due in U.S. pharmacies in October according to AbbVie, and a neurologist can say whether it suits them.