Taking a Different Approach to Slow Parkinson Disease Progression

Gennero Pagano, MD, MSc, PhD

This is a 2-part study. To view part 1, click here.

Treatment with prasinezumab (Roche), an investigational humanized monoclonal antibody previously known as PX002, resulted in a slight delay of motor progression in patients with Parkinson disease (PD) in part 2 of the phase 2 PASADENA study (NCT03100149). The investigational agent designed to bind to aggregated α-synuclein also led to more favorable disease trajectories for these patients.

In May 2021, Roche began a phase 2b study in patients with PD who have more advanced symptoms than that of PASADENA, called PADOVA (NCT0477331). PADOVA is enrolling 575 people who are on stable dopamine replacement medication and will use time to meaningful progression on the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale Part III as the primary outcome. Patients in that study will receive prasinezumab or placebo for 18 months, with motor function, clinical change, adverse events, pharmacokinetics, and antidrug antibodies all being assessed in secondary outcome measures.

Gennero Pagano, MD, MSc, PhD, expert medical director, Roche, sat down to provide his insight on the upcoming PADOVA study, as well as the important trends observed in the drug development space for PD. He also discussed the biggest takeaways from this year’s MDS Virtual Congress, September 17-22, 2021, and where the focus of research has been.

NeurologyLive: How will PADOVA help uncover more about prasinezumab’s ability to treat these patients?

Gennero Pagano, MD, MSc, PhD: Prasinezumab gave us some signal of effect on the motor signs of patients with PD. We’re going to continue to look at that signal specifically in PADOVA. We have a bigger study with a population in which patients are taking monoamine oxidase B inhibitors and symptomatic levodopa treatment. These patients would progress slightly faster than those who were treatment-naïve in PASADENA. If you think about a patient with Parkinson disease, most patients take symptomatic drug because it works. PADOVA will take a different approach. Rather than looking at an end point as a continuous matter, we’ll look at milestones. We will look at progression as something that you can delay, something that is meaningful for the patients, and then aim to translate this into the potential benefit.

For you, what are the most important aspects of PD drug development?

One of the biggest parts of momentum in Parkinson disease right now is that many companies and academic groups are trying to develop drugs that act on the fundamental biology of the disease. Alpha synuclein is one, but there are many others. There are many different approaches to studying alpha synuclein, but there are many other aspects in the biology of Parkinson disease that are characterized by cell death. Additionally, there are drugs that attack on other intracellular mechanisms. For example, in lysosomal dysfunction there’s a kinase that’s involved in the genetic parkinsonism. We sat that at MDS, where there were many posters that had different approaches to act on these different targets. There are other aspects of the biology that are liked to inflammation and the pathway of inflammation. Right now, there are several different drugs in the early stage that are different than what we currently have in the clinic. The probability of success for these trials is probably small, but if they’re successful, they are going to make a great impact for the patients.

What was your biggest takeaway from this year’s MDS Virtual Congress?

This year, I had an amazing opportunity to look at different types of research. There were strong new ideas on biomarker development, as well as drug development, which I mentioned before. There was also many different modalities and targets that represent the direction of the field. I see now that many people are working towards finding that drug or cure that can slow the progression of the disease. This is after many years in which people were developing symptomatic drugs. There have been many attempts in the past, but they were not successful. Overall, MDS Virtual Congress was a great platform in which there were many different types of initiatives and clinicians sharing data on biomarker and mechanisms that include biology, but also several on new drugs.

Transcript was edited for clarity.