The Parkinson’s disease (PD) pipeline has been hit significantly with a string of failures among its most anticipated mid-stage pipeline candidates. This news presents a challenge for similar disease-modifying therapies (DMTs) undergoing development such as Roche’s prasinezumab. It also amplifies that a major unmet need remains in bringing DMTs and neuroprotective agents to this market, which is currently dominated by symptomatic treatments, says GlobalData, a leading data and analytics company.

Biogen recently announced the discontinuation of its pipeline drug cinpanemab, after it missed its primary and secondary endpoints in its Phase II trial in PD. Similarly, Sanofi announced that venglustat failed in its Phase II trial leading the company to stop its further development for the PD indication.

Sarah Elsayed, Neurology Analyst at GlobalData, comments: “With Roche’s asset prasinezumab being the only monoclonal antibody (mAb) advancing into late-stage Phase IIb development, the results of its upcoming late-stage trial are now even more critical to the development of novel mechanisms of action (MOA) and strategies in future treatment of PD.”

Although these failures are disappointing, they come as no surprise. Key opinion leaders (KOLs) interviewed by GlobalData expressed doubts over the likelihood of success in trials investigating DMT for PD given the complexity of the disease and the need to target patients earlier in the disease progression.

Roche is currently developing its mAb prasinezumab after it has provided just enough evidence to proceed into its Phase IIb trial. It has a novel MOA similar to Biogen’s cinpanemab. Both target the α-synuclein protein, a hallmark pathological factor in PD, preventing their aggregation and potentially halting disease progression.

Elsayed continues: “This MOA was unanimously highly regarded by KOLs, stating that this approach, if approved, has the potential to revolutionize the treatment of PD. However, some were concerned that it might still be unclear whether targeting extracellular α-synuclein protein would offer enough benefit to PD patients. As such, all eyes will be on Roche’s prasinezumab trial as the remaining hope to resurrect the α-synuclein hypothesis. Updates on the initiation of the planned Phase IIb trial are expected to be announced in the second half of 2021. GlobalData expects that, if approved, prasinezumab could enter the US market by 2028 and that it will see fast initial uptake generating over $1.5bn in peak sales in the US.”

On the other hand, Sanofi took a different novel approach that is far less-studied with venglustat that acts by targeting the GBA mutation found in up to 10% of PD patients and associated with earlier onset of PD. Despite its failure in PD, the company will continue to study venglustat in other rare disorders such as Gaucher disease.

Elsayed adds: “Disease-modifying strategies range from those providing a neuroprotective role, to those that may reverse disease. GlobalData believes that neuroprotection is more within reach for the near future, although this area still proves to be very risky for pharmaceutical companies given the recent failure in trials. Still, the opportunity for developers to exploit alternative strategies is now imperative, given the significant unmet need in the PD space.”

Want to find out more? Send your questions to Beth Ralphs, PR Executive at GlobalData (pr@globaldata.com)