Hope remains that Roche’s prasinezumab can overcome recent string of failures in Parkinson’s disease

GlobalData Healthcare 22nd February 2021 (Last Updated February 22nd, 2021 09:02)

Hope remains that Roche’s prasinezumab can overcome recent string of failures in Parkinson’s disease
The PD pipeline was hit significantly with a string of failures among its most anticipated mid-stage disease-modifying therapies (DMTs). Credit: Shutterstock.

This month has seen the failure of main assets in the Parkinson’s disease (PD) pipeline. On 3 February, Biogen announced the discontinuation of its monoclonal antibody (mAb) pipeline drug cinpanemab following its failure to achieve primary and secondary endpoints in the Phase II proof-of-concept trial called SPARK in Parkinson’s disease (PD). The trial was investigating cinpanemab in 357 patients with PD, and the endpoints were to evaluate the drug’s impact on the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) after 52 and 72 weeks of treatment against placebo. Similarly, Sanofi announced on 5 February that its pipeline asset, venglustat, failed in its Phase II trial, leading the company to stop its further development for the PD indication. The two-part trial enrolled 270 patients, assessing improvements in MDS-UPDRS over 52 weeks. No further details of both trial results have been revealed so far. The PD pipeline was hit significantly with a string of failures among its most anticipated mid-stage disease-modifying therapies (DMTs). This news presents a challenge for similar pipeline candidates undergoing development. 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. With Roche’s asset prasinezumab being the only 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 the future treatment of PD.

Roche is currently developing its mAb prasinezumab after it has provided just enough evidence to proceed into a 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. This MOA was unanimously highly regarded by key opinion leaders (KOLs) interviewed by GlobalData, stating that this approach, if approved, has the potential to revolutionise 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 read out 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 $1.5B in peak sales in the US.

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

Although these failures are disappointing, they come as no surprise. KOLs expressed doubts over the likelihood of success in trials investigating DMT for PD given the complex pathophysiology of the disease and the need to target patients earlier in the disease progression.

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.