AbbVie recently announced a new phase 3 study (NCT04380142), called M15-736, which will measure the efficacy, safety, and tolerability of continuous subcutaneous infusion of ABBV-951.
David Standaert, MD, PhD
FOR YEARS, the combination of carbidopa and levodopa has been the standard of care for symptom management in patients with Parkinson disease (PD). As PD progresses, patients may experience fluctuations hour to hour from an ON state to an OFF state, during which they are slower, stiffer, and have more difficulty moving, leading to the need for treatments to make these fluctuations less drastic.
In January 2015, AbbVie received FDA approval for Duopa, the first and, to date, only treatment providing 16 continuous hours of carbidopa and levodopa together to help control motor fluctuations in advanced PD. The enteral suspension is administered using a small, portable infusion pump that delivers carbidopa and levodopa directly into the small intestine through a tube placed during an outpatient procedure.1
Now, AbbVie has announced that it will be conducting a new phase 3 study (NCT04380142), called M15-736, which will measure the efficacy, safety, and tolerability of continuous subcutaneous infusion of ABBV-951, its investigational soluble formulation of carbidopa and levodopa prodrugs, in patients with advanced PD (TABLE).
The 12-week study will have 2 treatment arms, one of which will receive ABBV-951 as a continuous subcutaneous infusion via external pump plus oral placebo capsules. In the second arm, participants will receive placebo solution as a continuous subcutaneous infusion plus oral capsules containing carbidopa/levodopa.2 The company expects the trial, which is currently recruiting, to enroll approximately 130 participants from 80 sites internationally.
TABLE. M15-736 Study Design
By providing continuous nonstop care, ABBV-951’s subcutaneous infusion/pump mechanism could represent a potentially landscape-altering treatment option, according to David Standaert, MD, PhD, chair of the Department of Neurology at the University of Alabama at Birmingham and a consultant for AbbVie. The new mechanism has several advantages over the percutaneous endoscopic transgastric jejunostomy (PEG-J) tube through which Duopa is administered, he says.
“The big difference from a patient perspective is that the drug can be delivered by a small subcutaneous needle that’s a continuous way of delivering levodopa. The need for levodopa comes out of what happens in advanced PD, where patients develop wearing off of their medications,” he told NeurologyLive®. “About 50% of patients at 5 years will experience wearing off, and there are ways to treat wearing off with oral medications, but many times we get to the point where you cannot control the wearing off anymore.” Standaert, who is also among the investigators for the phase 3 study, asserts that the size of ABBV-951 is another of its advantages.
Although patients with PD have benefited greatly from Duopa, issues with tube clogging and breakage can occur, and endoscopy is required when a tube needs replacement. If the ABBV-951 mechanism proves successful, it could be implemented in-office, with no need for the necessary gastroenterologist involvement and potential complications that come with a PEG-J tube.
Patients included in the study will be evaluated on change in ON time hours without troublesome dyskinesia from baseline up to week 12. Other key secondary outcome measures include changes in OFF time, score on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, sleep symptoms, and quality of life. Adult participants with advanced PD who complete the M15-736 study will be enrolled into an open-label extension (NCT04750226), in which researchers will assess adverse events (AEs) and changes in disease activity accompanying 96 weeks of treatment with ABBV-951.
Prior to the use of the Duopa pump, “many of these patients weren’t able to travel or go anywhere,” explained Standaert. “[After getting] the Duopa pump, they [can] travel, go out, be counted on, work— and they’re not fearful of wearing off. If the same can be achieved with a much simpler hardware setup, that would have a very impressive impact,” he emphasized.
According to Standaert, several ongoing phase 2b studies are looking at longer durations of the ABBV-951 therapy, but they have not reached an end point nor have any results been published. Results from a phase 1b study published in early 2020 demonstrated that ABBV-951 was well tolerated when delivered via continuous subcutaneous infusion. Among a cohort of 21 patients included in the safety analysis, AEs occurred in 19 patients (90.5%); 2 serious AEs (cellulitis and abdominal abscess) were reported in 1 patient who prematurely discontinued the study.3
Researchers found no clinically significant changes in laboratory, electrocardiography (ECG), or vital sign parameters. Exploratory efficacy results showed decreased OFF time compared with baseline during the 28-day study period and supported future investigations of ABBV-951.