Abbvie asks FDA to approve tavapadon as Parkinson’s treatment
Trial data show once-a-day medication eases motor symptoms
Abbvie has submitted an application to the U.S. Food and Drug Administration (FDA) seeking approval of tavapadon as a Parkinson’s disease treatment.
Clinical data have shown that the once-daily oral small molecule appears safe, reduces motor symptoms, and prolongs periods when these symptoms are well managed.
The application is based on TEMPO-1 (NCT04201093), TEMPO-2 (NCT04223193), and TEMPO-3 (NCT04542499), three Phase 3 clinical trials that tested tavapadon’s safety and effectiveness compared with a placebo in adults with either early-stage Parkinson’s who had minimal or no previous treatment (TEMPO-1 and TEMPO-2) or advanced disease (TEMPO-3).
Parkinson’s symptoms result from the progressive loss of nerve cells in the brain that produce dopamine, a chemical messenger essential for controlling movement. The standard treatment is oral levodopa, a precursor of dopamine. But its effectiveness can vary, and it may cause side effects such as dyskinesia (involuntary movements).
“For many people living with Parkinson’s disease, today’s oral standard of care isn’t effective enough to manage symptoms,” Roopal Thakkar, MD, Abbvie’s chief scientific officer and executive vice president of research and development, said in a company press release.
Activating dopamine receptors to ease motor symptoms
Tavapadon is a dopamine agonist that partially activates D1 and D5 dopamine receptors on nerve cells, mimicking dopamine. This is expected to ease motor symptoms.
The FDA submission draws on results from the TEMPO clinical development program, which assessed the efficacy, safety, and tolerability of tavapadon in a broad population of people with Parkinson’s. While the first three TEMPO trials have been completed, an open-label extension TEMPO-4 (NCT04760769) trial is ongoing to test flexible-dose tavapadon for more than one year.
“We recognize the physical and mental impact that Parkinson’s disease can cause and are committed to providing next-generation treatment options that will help individuals regain motor control and independence at all stages of this challenging disease,” Thakkar said.
In the TEMPO-1 clinical trial, 529 patients with early-stage Parkinson’s were randomly assigned to receive tavapadon at a fixed dose of 5 mg or 15 mg, or a placebo, once daily. The main goal was to watch for changes in the MDS-UPDRS Parts 2 and 3 combined score after about six months. In the MDS-UPDRS, a lower score means less severe motor symptoms.
Both doses of tavapadon significantly decreased this score over the placebo, corresponding to a decrease of 9.7 points with the 5 mg dose and 10.2 points with the 15 mg dose. In the placebo group, there were no significant changes over time.
The TEMPO-2 clinical trial involved 304 patients diagnosed with Parkinson’s within the past three years. They were randomly assigned to receive flexible-dose tavapadon or a placebo once daily for just over six months, with tavapadon adjusted to find the highest tolerated dose, from 5 mg up to 15 mg daily.
Tavapadon led to a greater decrease in the average combined MDS-UPDRS score compared with a placebo (10.3 points vs. 1.2 points). The difference appeared within one month and persisted through the end of the observation period.
TEMPO-3 tested the treatment in 507 adults with advanced Parkinson’s who were experiencing motor fluctuations — changes in how well treatment is working. Compared with a placebo, flexible-dose tavapadon as an add-on to levodopa increased on time — periods when symptoms are adequately controlled — by more than one hour, without troublesome dyskinesia.
In all three clinical trials, most side effects were transient and mild to moderate in severity. The most common side effects were nausea, headache, and dizziness for untreated patients, and nausea and dyskinesia for patients on adjunctive treatment with levodopa.
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