Pharma company, AbbVie, reports that its D1/D5 partial agonist, tavapadon, has met the primary and secondary endpoints in a pivotal Phase 3 trial.
The trial, called TEMPO-2, evaluated the investigational drug as a flexible-dose monotherapy for individuals with early Parkinson’s disease.
Tavapadon is the first partial agonist of the dopamine receptors D1/D5, helping to activate them in people with Parkinson’s disease.
About 10 million people globally suffer from Parkinson’s disease, with the number expected to double by 2050. It is known to be the fastest-growing neurological disorder in the world.
As a result of this disease, the brain loses its ability to produce the neurotransmitter dopamine. When the level of dopamine in the brain drops, there are not enough neurotransmitters to send electrical signals to the central nervous system. This results in a degeneration of nerve cells in the brain areas that control movement and balance. Affected individuals suffer from muscle tremors, rigidity, reduced movement, mood changes, loss of smell, and frozen facial expressions.
Dopamine receptors
By activating the dopamine receptors with dopamine agonists, some of the symptoms of Parkinson’s disease can be treated. Currently, D2/D3 dopamine receptor agonists tend to be used in this respect; they can cause common adverse effects, such as excessive sleeping during the day, confusion, hallucinations, light-headedness, low blood pressure, uncontrolled movements, or compulsive behaviors.
Research has shown, however, that selectively activating the dopamine receptors D1/D5 instead, can activate robust muscle functions and avoid the common adverse effects of D2/D3 dopamine receptor agonists. AbbVie’s tavapadon is a D1/D5 partial agonist.
“Parkinson’s disease imposes a profound burden on individuals living with this challenging neurological condition[...],” said Hubert Fernandez, global principal investigator and the James and Connie Brown endowed chair in movement disorders, professor of neurology and director of the Center for Neurological Restoration at Cleveland Clinic.
“Right now, there is still an unmet need for treatments that deliver efficacy while minimizing unwanted side effects. The results from TEMPO-2, and across the entire TEMPO clinical development program, add to the growing evidence which suggests that tavapadon has the potential to offer an important new option for individuals living with Parkinson’s disease.”
Trial findings
The TEMPO-2 Phase 3 trial evaluated the drug’s safety, efficacy, and tolerability at a once-daily, flexible dose of 5mg to 15mg.
The primary endpoint revealed a significant improvement in movement (from the baseline) compared to the placebo at week 26. The secondary endpoint showed that tavapadon demonstrated “statistically significant clinically meaningful improvement in motor aspects of experiences of daily living” compared to placebo.
“The positive results across all three Phase 3 TEMPO trials underscore the potential of tavapadon as a first-in-class D1/D5 partial agonist for the treatment of Parkinson’s disease,” said Primal Kaur, senior vice president of immunology, neuroscience, eye care, and specialty development at AbbVie.
“With these data in hand, we look forward to working with regulatory agencies to assess next steps, bringing us one step closer to providing tavapadon for those living with this chronic, debilitating disease.”
AbbVie plans to submit a New Drug Application (NDA) to the FDA in 2025.
