DUOGLOBE Interim Results: Intestinal Gel Cuts PD 'Off' Time

Damian McNamara

May 05, 2019

PHILADELPHIA — Levodopa-carbidopa intestinal gel (LCIG; Duopa, AbbVie Inc) significantly reduced patient-reported "off time" and significantly improved dyskinesia compared to baseline in Parkinson's disease (PD) in the DUOGLOBE study.

The mean decrease in off time was 4.1 hours at 12 months regardless of sex, age, or disease duration in the study of 139 people with advanced PD.

"This study represents an important step in the evolution of our knowledge about LCIG because it is examining patients treated in real-world clinical practice," lead author David G. Standaert, MD, PhD, the John N. Whitaker Professor and chair of neurology at the University of Alabama at Birmingham, told Medscape Medical News.

"What I would take from this is that — even in this less structured setting — LCIG still produces a robust decrease in 'off time' in these advanced patients," he added.

"This is the first prospective, multicenter, observational study that includes patients from the United States. It showed LCIG decreased patient off-time and reduced dyskinesia duration and severity," study coauthor Pavnit Kukreja, PharmD, US scientific director for neuroscience at AbbVie Inc in North Chicago, Illinois, said when presenting the findings here at the American Academy of Neurology (AAN) 2019 Annual Meeting.

Previous clinical trials of this agent featured structured entry criteria, procedures, and endpoints, Standaert said. "I think practitioners will be interested in this abstract because the kinds of patients and the conditions under which they were treated are similar to those one might encounter in a general or movement disorders neurology practice."

Although previous research pointed to a beneficial decrease in off time associated with LCIG in people with advanced PD, the researchers note that "prospective, multinational data on dyskinesia and other outcomes in routine clinical practice are limited."

The study was conducted at 55 sites in 10 countries. More than three quarters of the 139 participants were 65 years or older. Just more than half had had PD for 10 years or longer.

In addition to the approximate 4-hour mean decrease in off time, dyskinesia decreased a mean 12.7 points on the Unified Dyskinesia Rating Scale (UDysRS) measure at 12 months compared to baseline.

This is also the first study to assess the effects of LCIG on dyskinesia using the UDysRS, a scale developed by the International Parkinson and Movement Disorders Society. "It shows that not only does LCIG not increase dyskinesia, it actually seems to reduce it," Standaert said.

The researchers also observed improvements on the Unified Parkinson Disease Rating Scale (UPDRS) Part IV scores for off time duration through 12 months. In addition, dyskinesia-related disability and dyskinesia-related pain through 12 months, as well as dyskinesia duration at 6 months, improved compared to baseline.

The baseline Non-Motor Symptom Scale (NMSS) burden was "quite high" in these patients at 89%, Kukreja said. The researchers reported a marked improvement in nonmotor symptoms at month 3, which was sustained through month 12. The sleep/fatigue, mood/cognition, and gastrointestinal NMSS subdomains had the largest improvements.

Treating clinicians at practices around the world used different approaches to initiate and titrate the drug, and participants presented with a wide range of clinical features. "These findings provide further evidence for the real-world effectiveness on LCIG on motor fluctuations and duration and severity of dyskinesia," the researchers note.

LCIG was delivered via as an upper intestinal infusion via gastrojejunostomy tube. The therapy is a suspension of 20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate in an aqueous gel, administered continuously by a portable pump. LCIG is also known as carbidopa-levodopa enteral suspension in the United States. In 2015 the US Food and Drug Administration approved the agent to treat refractory motor fluctuations in people with PD.

"I think DUOGLOBE is going to teach us how patients will respond to LCIG in standard clinical care settings," Standaert said.

"What struck me about this data is, while there was improvement in off-time and a continuing benefit there, this is a continuous dopaminergic therapy — why doesn't it abolish all off-time? There was not a 100% improvement or even a 50% improvement in off time," asked Peter LeWitt, MD, professor of neurology at Wayne State University School of Medicine and director of the Parkinson's Disease and Movement Program at Henry Ford Hospital in West Bloomfield, Michigan, during the Q&A period.

Pavnit explained that she and her colleagues reported mean off-time, meaning there was variability in how patients responded.

"If the mean response was about 50%, does that mean some patients did not respond at all?" LeWitt continued.

"It's possible, but we didn't look at individual patient response," she replied. In phase 3 studies, responder rates varied from nonresponders to robust responders, who had more than 3 hours of off-time reduction, she added.

"I think it's a critical point," LeWitt said. He described LCIG as "a therapy that is invasive and certainly risky. They should know what their goal of improvement is and whether it's clinically meaningful."

An Option to Brain Stimulation

"This drug falls into the category of interventional therapies," session moderator Tanya Simuni, MD, chief of movement disorders in the Department of Neurology and professor of neurology at Northwestern University Feinberg School of Medicine in Chicago, told Medscape Medical News when asked to comment.

"I believe real-life experience is very important, and a 4-hour decrease in off time definitely exceeds other standard preparations," she added. "However, this drug is not compared to other standard drugs but to brain stimulation."

Therefore, the bar is high for this therapy, Simuni said. "My personal opinion is it is a potent therapy for a carefully selected group of individuals." For example, it could be an option to discuss with patients who decide not to pursue brain stimulation for cognitive or other reasons.

An unanswered question, she added, is whether LCIG decreases the need for other concomitant medications in this patient population.

AbbVie Inc sponsored the study. Kukreja is an employee of AbbVie. Standaert is a consultant and site investigator for AbbVie. Simuni does not have a relevant disclosure related to Duopa (AbbVie).

American Academy of Neurology (AAN) 2019 Annual Meeting. Abstract S4.004. Presented May 5, 2019.

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