Parkinson’s Disease (PD) is a complex, multi-system neurodegenerative disorder that affects movement control. Current treatments focus on the management of dopamine levels in the brain, with levodopa-based therapies remaining the standard of care in the PD market for the past half-century. However, the effectiveness of levodopa declines with time, and both motor and non-motor complications arise. This creates a significant opportunity for new entrants into the PD market, says GlobalData.
Christie Wong, Pharma Analyst at GlobalData, comments, “In the early stages of the disease, motor symptoms are well managed by levodopa, but as the disease progresses, reliable dosing becomes more difficult. Levodopa is a particularly difficult compound due to limitations in its absorption combined with a short half-life. Effective treatment for motor symptoms, including levodopa-induced dyskinesia, off-episodes, gait, and imbalance, remains an ongoing challenge in PD.”
In addition to the debilitating motor symptoms suffered by PD patients, an array of non-motor symptoms is also a recognized part of the disease progression. Among the non-motor complications of PD, the most difficult to treat are PD psychosis and PD dementia, which are primarily seen in advanced-stage patients. Key opinion leaders (KOLs) interviewed by GlobalData stated that between 15 per cent to 25 per cent of PD patients report experiencing hallucinations or delusions, and 80 per cent of patients with PD psychosis also have cognitive impairment.
Wong adds, “Acadia’s Nuplazid marks the first and only medication approved for the treatment of PD psychosis in the US since 2016. However, KOLs stated that Nuplazid is not very effective in managing the symptoms compared to other off-label antipsychotics. Besides that, Nuplazid has a boxed warning for the potential for increased risk of death in elderly people with dementia, which limits its use.”
The current medications used for the treatment of PD are limited to those providing symptomatic relief, leaving ample opportunities for new entrants into the PD market. The need for disease-modifying therapies is one of the highest unmet needs and was consistently highlighted by KOLs. They agreed that if a curative or disease-modifying agent was approved for PD, it could bring about a major shift in the way that patients are treated.
Luckily, several pipeline drugs that are in late-stage development may help address these longstanding unmet needs. For example, KOLs expressed excitement over continuous subcutaneous levodopa infusion systems offered by AbbVie’s ABBV-951 (foscarbidopa/foslevodopa) and NeuroDerm’s ND0612 (levodopa/carbidopa) to control motor fluctuations.
Sunovion’s ulotaront is investigated for the treatment of PD psychosis and Anavex’s blarcamesine is being studied for PD dementia. Prothena/Roche’s prasinezumab and Annovis’s buntanetap are suggested to possess disease-modifying properties through targeting α-synuclein protein, and in turn halting the disease progression. In addition, glucagon-like peptide-1 receptor agonists, Novo Nordisk’s Victoza (liraglutide) and Neuraly’s NLY01 are suspected to offer neuroprotection.
Wong concludes, “Any new medication that can improve motor symptom control, target PD dementia, or PD psychosis could have a huge clinical impact. However, due to the availability of only symptomatic treatment options in the PD market, it is likely that any late-stage pipeline agents would revolutionize the PD market if they demonstrated any neuroprotective or disease-modifying properties in the pivotal trial.