AbbVie launches Produodopa for advanced Parkinson’s in EU
The continuous infusion form of levodopa/carbidopa also is known as ABBV-951
Produodopa (foslevodopa/foscarbidopa), AbbVie‘s continuous under-the-skin (subcutaneous) infusion formulation of levodopa/carbidopa, now is available in the European Union (EU) for advanced Parkinson’s disease patients whose severe motor fluctuations and involuntary movements are not controlled well with standard therapies.
AbbVie initially was granted marketing authorization for Produodopa — also known as ABBV-951 — in 2022 through a decentralized procedure, which allows manufacturers to apply for simultaneous authorization in multiple EU member countries.
The Vyafuser infusion pump used with Produodopa earned its CE Mark late last year, which certifies that it conforms to safety, performance, and environmental requirements in the EU.
“People living with Parkinson’s disease experience daily challenges and uncertainty, especially as their disease progresses and symptoms are no longer adequately controlled,” Roopal Thakkar, MD, senior vice president, development and regulatory affairs and chief medical officer at AbbVie, said in a press release.
“This approval is an example of our unwavering commitment to this community by developing new, transformative therapeutic options for people experiencing advanced Parkinson’s disease, their families, and care partners,” Thakkar added.
Produodopa also has been approved in the U.K. and Japan. It previously was reviewed by regulators in the U.S., who requested more information about the infusion pump before it could be approved.
Parkinson’s disease is caused by the progressive loss of nerve cells that produce dopamine, an important brain-signaling chemical. Oral levodopa, which is converted to dopamine in the body, is a mainstay treatment.
It often is combined with carbidopa, which prevents levodopa from being converted into dopamine before it reaches the brain, helping to reduce the necessary dosage and ease side effects.
However, the effects of the treatment may wane over time, leading to prolonged off episodes, or motor fluctuations — when motor symptoms are not controlled well in between doses — and shorter on times, when symptoms are managed adequately. As a result, the need for additional doses of levodopa can lead to uncontrolled movements, or dyskinesia.
Seeking more options for the Parkinson’s comunity
“As Parkinson’s progresses, it can take a significant physical and emotional toll not only on the person but also on their family and care partners, who often play a critical role in their daily lives,” said Josefa Domingos, president of Parkinson’s Europe. “It is vital that the Parkinson’s community have more options that can help them manage their symptoms.”
Produodopa, delivered as a continuous subcutaneous infusion via a specialized pump for 24 hours a day, is designed to provide more stable levodopa levels, thereby minimizing off episodes. It contains prodrug versions of levodopa and carbidopa, which are inactive molecules that convert to the active medication once inside the body.
“When oral treatment no longer sufficiently helps with improvement in motor fluctuations, patients need alternative options,” said Angelo Antonini, MD, PhD, professor at the University of Padua in Italy. “Produodopa’s around-the-clock infusion allows for continuous delivery of levodopa, the gold standard of treatment.”
Data from three clinical trials
The EU launch of the medication was supported by three clinical trials, including a Phase 1 study that found Produodopa achieved comparable levels of levodopa in the bloodstream as a surgically implanted levodopa-carbidopa intestinal gel (LCIG), which AbbVie sells under the brand name Duopa/Duodopa.
A randomized, controlled Phase 3 clinical trial (NCT04380142), the M15-736 study, then enrolled 141 advanced Parkinson’s patients with uncontrolled motor fluctuations. Participants received either Produodopa with oral placebo, or continuous placebo infusion with oral immediate-release levodopa/carbidopa for 12 weeks (about three months).
Trial results showed that patients treated with Produodopa experienced significantly greater increases in on time without troublesome dyskinesia, Â and reductions in off time, compared to those who received oral levodopa/carbidopa.
Likewise, data from an open-label, global Phase 3 trial (NCT03781167), the M15-741 study, indicated that reductions in motor fluctuations were observed as early as one week after starting Produodopa and persisted for up to a year. The percentage of patients experiencing off episodes upon waking up also was reduced significantly.
Most side effects associated with Produodopa in clinical trials were mild or moderate, with the most frequent ones being infusion site reactions, hallucinations, falls, and anxiety.
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