A new experimental drug Lu AF28996 shows promise in advanced Parkinson’s

A new experimental drug from Lundbeck, a Danish pharmaceutical company based in Copenhagen that specialises in treatments for brain disorders, has shown early signs of improving motor fluctuations in people with advanced Parkinson’s. The drug, Lu AF28996, is now moving into a larger Phase II trial. The Phase Ib study involved 34 people with advanced Parkinson’s who continued to have motor fluctuations despite their existing treatment. They took Lu AF28996 twice a day. After six weeks, participants had, on average, 3.6 more hours of good ON-time per day. OFF-time was reduced by about 2.3 hours, and time spent ON with troublesome dyskinesia was reduced by about 1.2 hours. These changes were still seen after 18 weeks. Good ON-time was about 3.4 hours higher, while OFF-time was about 2 hours lower and troublesome dyskinesia about 1.4 hours lower than at the beginning of the study. Lu AF28996 works differently from levodopa. It stimulates both D1 and D2 dopamine receptors, which are involved in controlling movement. Researchers are investigating whether this approach can provide more consistent movement control. Participants also reduced their daily levodopa dose during the study. However, this does not mean the drug can replace levodopa. Medication changes were part of the study, and the small design means this finding needs further investigation. The main limitation is that this was a small, open label Phase Ib study with no placebo group. Everyone knew they were receiving the experimental drug. This makes it difficult to separate the effect of the drug from other factors, including changes in treatment and expectations. Side effects included nausea, dizziness and falls. Lundbeck reported no unexpected safety concerns, but a study involving only 34 people cannot establish the safety of a new drug. The next step is therefore much more important. The Phase II trial will include around 150 people and will be randomized, double blind and placebo controlled. Researchers will mainly look at whether Lu AF28996 increases daily good ON-time after 19 weeks. The early results are interesting, particularly because the reported changes involve the problems that can become increasingly difficult in advanced Parkinson’s: OFF-time, troublesome dyskinesia and loss of reliable ON-time. But at this stage, Lu AF28996 remains an experimental treatment. The Phase II trial will provide a much clearer test of whether these early improvements are genuinely caused by the drug.