The oral, specific dopamine agonist met its primary endpoint in the trial, which is the second of three phase 3 trials testing tavapadon for treatment of Parkinson’s disease.
AbbVie acquired Cerevel Therapeutics earlier this year and tavapadon is the company’s lead candidate drug. Cerevel originally spun out from Pfizer in 2018 and has a neurology focus with candidates for schizophrenia, epilepsy, Parkinson’s and other neuropsychiatric indications in development.
The TEMPO-1 trial assessed the ability of fixed dose tavapadon, a highly selective partial agonist of the dopamine D1 and D5 receptors, for treating Parkinson’s symptoms as a fixed dose monotherapy.
The double-blind, randomized, placebo-controlled trial enrolled 529 people with early-stage Parkinson’s disease. The participants were assigned to receive one of two fixed, tablet doses of tavapadon, 5 mg or 15 mg, or placebo per day for 26 weeks.
The trial met its primary endpoint of a statistically significant reduction in the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III combined score in those treated with tavapadon versus placebo. Overall, the scores at 26 weeks were +1.8, -9.7 and -10.2 for the placebo, 5 mg/day, and 15 mg/day groups, respectively.
The main secondary endpoint of the trial, an improvement in the MDS-UPDRS Part II score (relating to movement symptoms), was also achieved in both tavapadon groups.
These results back up results from the TEMPO-3 trial, which tested tavapadon as an add-on therapy to levodopa and which also met its primary endpoint earlier this year. The final trial, TEMPO-2 is testing flexible dose tavapadon, also as a monotherapy, and is expected to read out before the end of the year.
“The TEMPO-1 data, coupled with the previously reported TEMPO-3 adjunctive trial findings, further support the potential of tavapadon for people living with Parkinson’s disease,” said Primal Kaur, senior vice president, immunology, neuroscience, eye care and specialty development, AbbVie, in a press statement.
“This marks a significant step forward in our commitment to enhancing our neuroscience portfolio following the strategic acquisition of Cerevel Therapeutics and further demonstrates our dedication to supporting patients at all stages of this challenging neurological condition. We look forward to sharing additional data later this year from the TEMPO-2 monotherapy trial.”
Finding new treatments for Parkinson’s
Parkinson’s is the second most common neurodegenerative disease and is thought to affect 1-2 people per 1000. It is significantly more common in older individuals and men are 40% more likely to be affected than women.
There is no cure for Parkinson’s, but a number of different treatments are approved to combat the neurological symptoms, which include tremor, movement difficulties and also impact mood and cognition.
The motor symptoms of Parkinson’s are known to be due to reduced dopamine production in the brain and levodopa, a precursor of dopamine, can be used as a treatment for the symptoms. It can help significantly with the motor symptoms, but also has significant side effects such as nausea, vomiting and low blood pressure. Prolonged use can also result in irregular efficacy of the drug and dyskinesias due to the treatment.
Dopamine agonists were developed later and have similar effects to levodopa but tend to be prescribed as a first treatment in early Parkinson’s before levodopa as they tend to be less effective at managing disease symptoms but have less drug-related complications.
Although there are a few dopamine agonists already on the market, AbbVie is hoping to compete with tavapadon because its specificity means it can help with symptoms with a minimal side effect profile. Indeed, in both phase 3 studies that have read out so far, side effects have been mild or moderate.
These results and those from the final phase 3 trial will be used to support regulatory submissions for tavapadon going forward.