Prasinezumab

Hope on the horizon: What we know about prasinezumab, a new treatment in clinical trials for Parkinson’s disease

Νόσος Πάρκινσον έρευνα νέα Πρασινεζουμάμπη

At Parkinson Pharos, our mission is to empower patients with Parkinson’s and their families through trustworthy, easy-to-understand information, and strong community support. Today, we are exploring an exciting potential treatment for Parkinson’s disease called prasinezumab. Prasinezumab is currently being tested in clinical trials. We will explain how it works, what researchers have discovered so far, and what is coming next.

Article Summary

Results from the two studies (PASADENA & PADOVA)

In both studies, prasinezumab did not meet its primary goal (slowing the worsening of Parkinson’s symptoms).
However, positive indications were observed suggesting slower disease progression in certain patient groups (these results need to be confirmed).
In the PASADENA study, there was improvement in daily activities and sleep, along with encouraging digital health measurements.

Number of participants and countries

More than 900 patients from multiple countries (USA, Canada, UK, France, Germany, Italy, Spain, Austria, Poland, Luxembourg) have received prasinezumab, some for over five years.

Positive findings supporting further research

Slower progression of motor symptoms and improvement in some non-motor symptoms.
Better overall sense of health in some patients, particularly those already taking levodopa.

Safety

Prasinezumab is generally well tolerated. The most common mild side effects were rash, nausea, headache, and back pain.

What is prasinezumab?

Prasinezumab is a special kind of medicine called a monoclonal antibody. Simply put, it is a protein produced in a laboratory that targets a specific protein in the body. Prasinezumab targets alpha‑synuclein (α-synuclein). In people with Parkinson's disease, α-synuclein clumps together in the brain, forming what are called “aggregates”.

Think of α‑synuclein usually helping traffic (signals) flow in the brain, but when it forms “traffic jams” (clumps) messages cannot get through easily, leading to movement and thinking problems.

Prasinezumab is designed to bind to these clumps and help stop them from growing and spreading. The hope is this might slow the disease from getting worse (disease progression).

Who is developing prasinezumab?

This promising treatment is being developed by Roche together with Prothena. These are companies that specialize in researching and developing new medicines.

What have previous studies shown so far?

Prasinezumab has been studied in several clinical trials. Two important Phase 2 studies with prasinezumab are:

PASADENA trial.
PADOVA trial.

Summary of the PASADENA and PADOVA studies

Study name	PASADENA	PADOVA
Study Phase	Phase 2	Phase 2
Main goal	Researchers wanted to test if prasinezumab compared to a placebo* (dummy medicine) can slow symptoms (both the movement related and non-movement related symptoms) from getting worse.	Researchers wanted to compare how long it took movement symptoms to get worse between people who received prasinezumab compared to people who took a placebo (dummy medicine).
About the people who took part in the study	A total of 316 people with early stage Parkinson’s disease took part: There were 213 men and 103 women. They were between 40 and 80 years old (mean age 59.9 years old). They were from the United States, France, Austria, Germany, and Spain.	A total of 586 people with early stage Parkinson’s disease took part: There were 372 men and 214 women. They were between 50 and 85 years old (mean age 64.2 years old). They were from the United States, Italy, France, Poland, Austria, United Kingdom, Canada, and Luxemburg.
Design of the study	The study had 3 Parts. Part 1 and 2 each lasted one year. Part 3 is ongoing and will last 5 years in total. During Part 1 people took prasinezumab or a placebo. Part 1 was double-blind. During Part 2 and Part 3 all participants received prasinezumab (open-label*). People who took placebo in Part 1 were switched to prasinezumab in Part 2 and Part 3.	The study had 2 Parts. Part 1 lasted 18 months. Part 2 is ongoing and will last 24 months in total. During Part 1 people took prasinezumab or a placebo. Part 1 was double-blind. During Part 2 all participants received prasinezumab (open-label*). People who took placebo in Part 1 were switched to prasinezumab in Part 2.
How the medicine was given	Prasinezumab and placebo was given as an injection in the vein (intravenously) once every month.	Prasinezumab and placebo was given as an injection in the vein (intravenously) once every month.
Doses	During Part 1 and Part 2 prasinezumab was given at 1500 mg or 4500 mg. During Part 3 all participants received 1500 mg.	Prasinezumab was given at 1500 mg dose.

*A placebo (dummy medicine) looks like real medicine but has no active real medicine in it. It is used in studies to check if the real medicine works better than taking nothing at all.

**Double-blind means that neither the study doctors nor the people who took part in the study knew who was given prasinezumab or a placebo.

*** Open-label means that both the study doctors and the people who took part in the study knew that everyone was given prasinezumab.

What did the PASADENA and PADOVA studies find?

PASADENA study

The main goal of the PASADENA study was to see if prasinezumab compared to a placebo, could slow down the worsening of Parkinson’s symptoms as measured by a scale called the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), which looks at movement (motor) and non-movement (non-motor) symptoms.

Μain results of Part 1 of the PASADENA study

The overall results from the first 12 months (Part 1) showed:

No difference between the groups receiving prasinezumab compared with the group receiving a placebo, in the worsening of Parkinson's symptoms (MDS-UPDRS sum of Parts I, II, and III) during the first 12 months of the study. Therefore, the study’s main goal was not met.
However, researchers looked at other measurements and observed some positive results. For example, they observed that prasinezumab might improve study participants with quickly worsening Parkinson's disease.

It is really important to understand that when a study’s main goal is not met, these other positive results, even if they look promising, might be due to chance. Good studies try to confirm any new positive results with bigger trials before doctors can recommend a new treatment.

Results of Part 3 of the PASADENA study

At the last part (Part 3) of the PASADENA study, which is ongoing, all study participants are receiving prasinezumab (1500 mg). Analysis of the results of the first 4 years of the last part of the study showed:

Study participants had continued slowing of movement symptom worsening over 4 years compared to a group of similar people living with Parkinson’s who did not take part in the study.
There were positive results about how people felt about their daily activities (MDS-UPDRS Part II) and even some non-motor symptoms like sleep problems (MDS-UPDRS Part I sleep scores).
Positive changes at measures from digital health tools.

These results look promising, but participants who received prasinezumab in this last part of the study were compared with people with Parkinson’s disease from outside the study, not a control group inside the study. Therefore, additional studies need to be done to confirm the results are not random.

The PADOVA trial

The main goal of the PADOVA study was to see if prasinezumab compared to a placebo could delay the worsening of movement Parkinson symptoms, as measured by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS Part III).

Main results of Part 1 of the PADOVA study

The overall results from the first 18 months (Part 1) showed:

There was no difference between study participants who received prasinezumab compared to study participants who received a placebo in the worsening of motor symptoms during the first 18 months of the study. Therefore, the study’s main goal was not met.
However, as with the PASADENA study, when researchers looked at additional measurements, they found that prasinezumab had some positive effects:
- Possible slower worsening of movement.
- More positive feelings about overall condition.
- These positive results were especially seen in people already taking levodopa.

Prasinezumab safety results from the PASADENA and PADOVA studies

When testing a new medicine, understanding its adverse events is very important. Adverse events are any unwanted health problems a person might get from a medicine.

Prasinezumab has been generally well tolerated in patients with Parkinson’s disease in previous studies, including the PASADENA and PADOVA studies. No unexpected safety problems were reported in over 900 participants, many of whom took prasinezumab for up to 5 years.

Common adverse events

The most common adverse effects of prasinezumab reported in the PASADENA and PADOVA studies include:

Reactions that happened during or soon after the medicine was given: rash and feeling sick (nausea).
Cold-like symptoms (nose and throat inflammation).
Headache.
Back pain.

Serious adverse events

Serious adverse events are more severe health problems that people had in the study. Serious adverse events were rare and happened in a small number of participants in the PASADENA and PADOVA study.

Why a new study and what questions remain?

Even though the PASADENA and PADOVA studies missed their main goal, the positive results are encouraging and important. This is why Roche is continuing the open-label parts of the PASADENA and PADOVA studies. Also, Roche has decided to start a larger study, a Phase 3 clinical trial in a larger patient population with early-stage Parkinson’s patients. Phase 3 clinical trials usually involve thousands of patients. The enrollment details are not available, yet.

These ongoing and future studies aim to:

Further study the positive effects that were observed in the previous clinical trials.
Better understand which patients living with Parkinson’s might benefit most from prasinezumab, perhaps by using biomarkers (biomarkers are signals in the body that show disease or if a medicine is working). This could lead to better decision on which medicine works best for every patient.
The long duration of these studies allows for stronger changes in symptoms to be observed, which can help find the true effect of the medications.

Even if prasinezumab fails to show a slowing of Parkinson’s disease, it will still give researchers important information. It may help researchers better understand the role of α-synuclein in Parkinson’s to design better future therapies. There are also many other medications that are now developed which target α-synuclein.

The big picture: How could this improve quality of life?

If prasinezumab is successful in ongoing and future studies it could truly slow down or even stop the worsening of Parkinson’s disease. This is the hope, but it is not proven yet. More research is needed. Nevertheless, it is an important step, compared to available medications and therapies, which only manage symptoms without targeting the root cause of the disease. If prasinezumab is successful, that could mean:

More years of independence and better movement.
Slower progression of thinking or memory problems.
Fewer other medications needed.
Better non-movement symptoms, like sleep.
Feeling better about overall health.

Stay tuned with Parkinson Pharos!

The journey to new Parkinson's treatments is long and takes careful science. While prasinezumab has faced challenges in the previous studies, the persistent positive results offer reasons for optimism.

We at Parkinson Pharos will continue to bring you the latest, most reliable, and easy-to-understand information so you can stay informed and empowered. Keep an eye out for updates on the ongoing studies and future research! And please tell us what topics and information would help you most – we learn from you!