Last updated Feb. 16, 2023, by Marisa Wexler, MS
Fact-checked by Marta Figueiredo, PhD
What is ABBV-951 for Parkinson’s disease?
ABBV-951 (foslevodopa/foscarbidopa) is an experimental under-the-skin, or subcutaneous, therapy AbbVie is developing as a treatment for motor fluctuations in advanced Parkinson’s disease.
AbbVie submitted an application to the U.S. Food and Drug Administration (FDA) for the therapy’s approval in May 2022.
How does ABBV-951 work in Parkinson’s disease?
Parkinson’s disease is caused by the death and dysfunction of nerve cells in the brain that are responsible for making the chemical messenger dopamine that’s essential for motor control.
Oral levodopa, a precursor of dopamine that can reach the brain, is a mainstay Parkinson’s treatment that works by providing the raw materials for making dopamine. However, traditional tablet forms may result in variable doses of levodopa reaching the brain, due to variable absorption in the digestive system.
As such, the therapy is commonly combined with carbidopa, which prevents levodopa from being converted into dopamine before it reaches the brain. The combination increases the levels of levodopa reaching the brain and helps reduce levodopa doses and its associated side effects.
While levodopa/carbidopa therapy is generally effective at controlling Parkinson’s symptoms, patients commonly end up experiencing off episodes, especially in more advanced stages of the disease. Off episodes are periods when levodopa-based treatments stop working and motor symptoms return.
ABBV-951 is a soluble, under-the-skin formulation of foslevodopa and foscarbidopa, which are prodrug versions of levodopa and carbidopa, respectively. Prodrugs are inactive molecules that are metabolized into the active medicine once they are inside the body.
The therapy is administered continuously and directly under the skin, where it can be absorbed into the bloodstream, through a minimally invasive and convenient mode. By avoiding the digestive system, ABBV-951 is expected to deliver a more consistent dose of levodopa to the brain and start working faster than the oral form of the medication, thereby reducing off time.
This delivery method has also the potential to be as effective as AbbVie’s Duodopa or Duopa, also known as levodopa/carbidopa intestinal gel (LCIG), without the need for surgery.
Duodopa is an approved therapy to reduce motor fluctuations in Parkinson’s patients. It delivers a continuous infusion of levodopa/carbidopa through a tube directly to the small intestine, bypassing the stomach and allowing the therapy to be more quickly absorbed. However, this route requires surgery to place the tube.
How will ABBV-951 be administered in Parkinson’s disease?
In late-stage clinical trials, the formulation of ABBV-951 contains foslevodopa and foscarbidopa in a 20:1 ratio, and is being continuously administered into the abdomen for up to three consecutive days via an under-the-skin infusion set connected to a portable pump. The specialized pump is designed to allow patients to change infusion rates or doses.
ABBV-951 in Parkinson’s disease clinical trials
AbbVie’s application to the FDA is supported mainly by data from two Phase 3 clinical studies.
Phase 3 trial
A Phase 3 clinical trial (NCT04380142) enrolled 174 adults with advanced Parkinson’s at 65 sites across the U.S. and Australia. All of the participants were experiencing at least 2.5 hours of daily off time on standard oral levodopa/carbidopa treatment.
Participants were randomly assigned to receive either ABBV-951 and an oral placebo or oral levodopa/carbidopa and an under-the-skin placebo infusion for 12 weeks.
The trial’s main goal was to assess changes in good on time, when symptoms are adequately controlled without troublesome dyskinesia, or uncontrolled movements. Dyskinesia is a common side effect of oral levodopa/carbidopa therapy.
Results showed ABBV-951-treated patients experienced a significantly greater increase in daily good on time compared with those on oral levodopa/carbidopa (2.72 vs. 0.97 hours). Consistently, daily off time dropped by an average of 2.75 hours with ABBV-951 and by less than an hour with oral treatment.
Also, a smaller proportion of patients on the experimental therapy reported being off at the time of waking relative to those on oral levodopa/carbidopa (17% vs. 63%). This difference was observed despite the fact that patients on the oral therapy could take a nigh-time dose if needed.
Safety-related findings were generally comparable between ABBV-951 and oral levodopa/carbidopa.
Participants who completed the trial had the option to enroll in an open-label extension study (NCT04750226), in which all participants will be treated with ABBV-951 for up to nearly two years and monitored for long-term outcomes.
Long-term Phase 3 trial
Another Phase 3 trial (NCT03781167) recruited 244 Parkinson’s patients who were experiencing 2.5 hours or more of off time per day while on oral levodopa/carbidopa treatment — the average daily off time was nearly six hours. All participants were treated with ABBV-951 for one year.
Results showed that after a year on ABBV-951, average daily off time was reduced by 3.39 hours, and daily on time increased by 3.58 hours on average. Also, the proportion of patients who reported unusual slowness and difficulty moving upon waking (morning akinesia) dropped from 77.7% to 19.4%.
Patients who completed the one-year trial could choose to continue treatment for up to nearly two years in an extension study (NCT04379050) that is collecting long-term data on the safety and efficacy of ABBV-951.
AbbVie is sponsoring a Phase 1 trial (NCT05094050) that aims to assess the pharmacological properties of ABBV-951 when administered to the arm, thigh, or flank, when compared with the standard abdomen.
Up to 12 Parkinson’s patients experiencing at least 2.5 hours of daily off time with standard levodopa-based therapy will have ABBV-951’s under-the-skin pump placed at each location for two consecutive days. Treatment will have a total duration of up to 12 days.
Recruitment is ongoing at sites in the U.S. Participants who complete the study will have the option to continue receiving ABBV-951 treatment in an open-label extension study
Common side effects of ABBV-951
The most common side effects reported in ABBV-951 clinical trials include:
- infusion site reactions like skin reddening, pain, and swelling
- balance issues and falls
- peripheral swelling, or swelling of the lower legs or hands.
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