February 14, 2021

Impact: High

During its Q4 2021 earnings call, Prothena gave an update on its prasinezumab clinical program for Parkinson’s disease. During the clinical overview, Prothena highlighted that prasinezumab specifically targets the C-terminus of alpha-synuclein and is the “first antibody to show significant slowing of motor progression and improvements in imaging biomarkers.” The company stated that preclinical studies had shown that targeting the N-terminus was suboptimal and proposed it as a potential hypothesis on why Biogen’s cinpanemab failed, a point later reiterated during the Q&A.

Prothena remains very encouraged by efficacy signals observed in its Phase 2 PASEDENA Part 1 study. Data from pre-specified exploratory subgroup analysis from the PASEDENA Part 1 study will be presented at the ADPD conference in March. Prothena expects Roche to present results from PASEDENA Part 2 at a future medical conference.

Roche is expected to initiate the Phase 2b study of prasinezumab in Parkinson’s disease in Q2 2021 with details to come in Q2 as well. Prothena will earn $60M clinical milestone payment upon dosing of first patient.

Q & A

Any other differences between Prasinezumab and cinpanemab, other than epitope? 

  • Hard to make a direct comparison other than epitope, however Prothena’s preclinical data shows that targeting C-terminus is much more effective and this has been consistent with other antibodies they have tested. The company believes that its antibody selection criteria based on epitope, affinity, and efficacy has led to successful transition of translation from preclinical to clinical program.

On upcoming prasinezumab Phase 2b study? 

  • Anticipate Roche getting Phase 2b up and running. Expect at ADPD that there will be additional analysis of the PASEDENA Part 1 study as well as Roche presenting on PASEDENA Part 2.

inThought Analysis

Prothena and Roche have yet to share details on the upcoming Phase 2b study of prasinezumab in early Parkinson’s disease and it seems like the companies might not share details until right before trial initiation. It is unclear how Prothena/Roche will pivot from the unmet primary endpoints in the PASEDENA trial to a more successful study, however, more details might be forthcoming at AD/PD where additional data from PASEDENA Part 1 will be presented.

Additionally, Prothena poses some interesting color to the alpha-synuclein targeting approach for PD by stating that antibodies that target the C-terminus were found to be more robust and effective in targeting misfolded alpha-synuclein. The company believes this binding differential has clinical value, given the failure of Biogen’s N-terminal targeting cinpanemab.

Source: Prothena Earnings Release, Prothena Earnings Presentation