FDA Approves AbbVie's Tavapadon (Juvmo), a D1/D5-Selective Dopamine Agonist for Parkinson's Disease
核心洞察
The U.S. FDA approved AbbVie's tavapadon, sold as Juvmo (搜索), a once-daily oral dopamine agonist for adults with Parkinson's disease (搜索).
Tavapadon selectively targets D1 and D5 receptors concentrated in movement circuits, unlike older agonists such as pramipexole and ropinirole that act mainly on D2 receptors.
In two trials of more than 800 early-stage patients, about 45% and 46% on tavapadon improved markedly versus 12% and 19% on placebo.
The U.S. Food and Drug Administration (搜索) has approved tavapadon, an oral dopamine agonist developed by AbbVie, for the treatment of Parkinson's disease (搜索) in adults. The drug will be sold under the brand name Juvmo (搜索) as a once-daily pill, according to the FDA's website. More than 11 million people worldwide live with Parkinson's disease, according to AbbVie.
Parkinson's is a long-term brain condition that gradually damages movement control, often causing tremors, stiffness and balance issues. Since the 1960s, treatment has revolved around dopamine, the brain chemical whose producing cells progressively die in patients. Levodopa, the mainstay therapy, contains a substance the body converts into dopamine. Alongside it are dopamine agonists such as pramipexole and ropinirole, which mimic dopamine and bind directly to its receptors.
A Different Receptor Target
Dopamine has five receptor types divided into two families, involved in movement, sleep, appetite, mood, attention and thinking. Each family is more prevalent in different brain regions, so a drug aimed at one family behaves differently from one aimed at the other. Existing agonists act mainly on D2 receptors, which are also found in brain regions associated with reward, thinking and automatic regulation. That distribution helps explain side effects including compulsive behaviors, sudden sleep attacks and swelling in the legs.
Tavapadon also is a dopamine agonist but targets D1 and D5 receptors. D1 receptors are concentrated mainly in brain circuits that drive voluntary movement. Researchers have tried for decades to develop a drug that selectively activates them. Early attempts showed the concept could work, but the compounds broke down too quickly in the body, were poorly absorbed as pills and caused severe involuntary movements; one also caused a drop in blood pressure.
Tavapadon was designed to overcome those problems. It is resistant to the enzymes that break down dopamine and remains in the body for a long time, allowing once-daily dosing. It also only partially activates the receptor. According to its developers, this more restrained activation is intended to improve movement without causing overstimulation, which can lead to involuntary movements.
The drug was originally developed by Pfizer, later transferred to biotech company Cerevel, and came to AbbVie when it acquired Cerevel in 2023 for $8.7 billion.
Trial Results
Two large trials enrolled more than 800 patients diagnosed within the previous three years who had received little or no treatment. Some received tavapadon and others placebo for about six months. In both trials, the drug produced statistically significant improvements in movement and daily functioning.
In the first trial, about 45% of patients who received the drug reported a marked improvement in their condition, compared with 12% of those on placebo. In the second trial, the figures were 46% and 19%, with improvement appearing after about five weeks of treatment.
A third trial addressed a problem familiar to patients who have lived with Parkinson's for years: after prolonged levodopa treatment, the effect of each dose wears off before the next is due and symptoms return. The trial included 507 such patients. Adding tavapadon to their treatment gave them about one additional hour a day of good functioning without troublesome involuntary movements compared with the placebo group.
Medical centers in Israel also participated in the trials. Prof. Tanya Gurevich, director of the Movement Disorders Unit at Ichilov Medical Center and the principal investigator for the study in Israel, said: "Unfortunately, no treatments have yet been approved that have been shown to slow the progression of the disease. Against this background, tavapadon represents a new generation of dopamine agonists, with the potential to reduce side effects such as involuntary movements and impaired impulse control. It is a promising treatment option that may benefit patients in both the early and advanced stages of the disease, and we hope it will soon be available in Israel as well."
She added: "Based on the experience accumulated at the Israeli centers that participated in the study, both patients and researchers felt that tavapadon may offer an advantage over existing treatments in the same drug class."
Tolerability and Open Questions
The most common side effects in trials were nausea, dizziness and headache. In an extension study in which 991 patients took the drug over a longer period, each of those side effects occurred in about 10% of participants.
Not all participants remained in the studies. In the first trial, about one-third of those who received the higher dose discontinued treatment before the study ended, compared with about 15% in the placebo group. In the second trial, about one-quarter of patients receiving the drug dropped out, most during the period when the dose was being gradually increased.
Side effects commonly associated with older drugs were rare. Drowsiness was reported in 4% of patients receiving the drug versus 3% on placebo, while the rate of compulsive behaviors was similar to placebo. No involuntary movements were reported in either group. The researchers noted that the relatively short follow-up of about six months does not allow conclusions about long-term tolerability, and that an extension study is intended to examine that question.
The major question is how tavapadon will compare with drugs patients already take. In all trials it was compared only with placebo, not with another active drug, so its purported advantage in side effects has not been tested directly against older medications. In an article in The Lancet Neurology, experts wrote that it is still too early to determine the drug's place relative to existing treatments, and that larger, longer trials will be needed.
AbbVie has not said when it will launch the drug or how much it will cost, and did not respond to a request for comment from Reuters. Analysts expect the drug to enter use gradually, in part because of negotiations over coverage under U.S. government health insurance programs. It is also unclear when the drug will become available in Israel.
This is not AbbVie's first Parkinson's treatment in recent years. About two years ago the company launched Produodopa, a small pump that continuously infuses levodopa under the skin around the clock. The treatment does not require surgery and, according to the company, improves patients' quality of life by helping control symptoms at night and preserve daily functioning.