Phase 2b Trial of Prasinezumab in Patients With Early Parkinson’s Expected by 2021

Roche, in partnership with Prothena, will launch a Phase 2b clinical trial to evaluate the effectiveness of prasinezumab (PRX002/RG7935) — an antibody against the alpha-synuclein protein — in people with early stage Parkinson’s disease, including those on stable levodopa treatment.

The decision was based on positive data from a previous Phase 2 trial, PASADENA (NCT03100149), which, despite failing to meet its main goal of demonstrating prasinezumab can slow the progression of both motor and non-motor symptoms, showed the therapy significantly reduced motor function decline and improved disease biomarkers.

Prasinezumab becomes the first antibody of its kind to advance into late-stage clinical development. Additional details of the new clinical trial should be announced in the first half of 2021.

“We are very encouraged by the results from PASADENA, demonstrating significant slowing of motor progression and improvements on imaging biomarkers consistent with disease modification, as this provides a rich dataset to directly inform and de-risk this next late-stage study,” Gene Kinney, PhD, president and CEO of Prothena, said in a press release.

“Results from the PASADENA study are part of a growing clinical body of evidence suggesting antibodies that optimally target misfolded proteins can result in clinically meaningful benefit,” Kinney added.

Developed by Prothena in collaboration with Roche, prasinezumab is designed to selectively eliminate the toxic alpha-synuclein aggregates that contribute to Parkinson’s progression by inducing an immune response against them.

After a Phase 1b trial (NCT02157714) showed that prasinezumab safely and effectively lowered alpha-synuclein blood levels in patients with Parkinson’s, Roche launched PASADENA to determine if the therapy also could prevent disease symptom progression.

The international, two-part trial included 316 people with early stage Parkinson’s, who had been diagnosed in the past two years, were not on dopaminergic therapy (such as levodopa), and were not expected to need it for at least one year.

In the first part, participants were assigned randomly to receive an into-the-vein infusion of one of two doses of prasinezumab (1,500 mg or 4,500/3,500 mg, depending on body weight), or a placebo, once every four weeks for one year.

Those who completed the one-year treatment course were eligible to enter the trial’s second part, in which all participants either continued treatment or switched from placebo to one of the two therapy doses. Patients completing Part 2, including a 12-week treatment-free follow-up visit, may choose to continue treatment with prasinezumab for an additional five years.

In April, Roche announced that PASADENA failed to meet its main goal of showing that prasinezumab was superior to placebo at lessening the progression of motor and non-motor symptoms — measured by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score — after one year (the end of part one).

However, the company noted that prasinezumab showed signs of effectiveness on multiple pre-specified secondary and exploratory measures — data that were presented at the International Parkinson and Movement Disorder Society’s MDS Virtual Congress 2020.

The results showed that prasinezumab (pooled doses) significantly reduced patients’ motor function decline by 35% and significantly delayed clinically meaningful worsening of motor symptoms, compared with a placebo. These changes in motor function were assessed based on the MDS-UPDRS Part III — motor examination.

Positive signals on motor function also were confirmed using Roche’s PD Mobile Application v2. — a smartphone app that includes several motor function tests and passive monitoring. It indicated that prasinezumab lowered motor function decline by 25%.

In addition, both prasinezumab doses were associated with better cognitive performance, greater physician- and patient-perceived global improvements, when compared with a placebo. The therapy also improved blood flow in the putamen, a brain region highly affected in Parkinson’s, suggesting an impact on the underlying biology of disease progression.

Prasinezumab was generally safe and well-tolerated, with most side effects being mildly or moderately severe and with similar rates across patient groups.

In a press release announcing these data, Joseph Jankovic, MD, professor of neurology and the director of Baylor College of Medicine’s Parkinson’s Disease Center and Movement Disorders Center, in Texas, said that “these results are extremely encouraging for patients with Parkinson’s disease and the clinicians who treat them and warrant additional clinical investigation.”

“There is an urgent need for new therapies that target the underlying cause of this debilitating disease and, unlike symptomatic therapies, slow its relentless progression,” Jankovic added.

These positive findings supported the planned launch of a Phase 2b trial, designed to confirm the motor function benefits in a similar early-stage patient population, but now also including patients on stable levodopa therapy — the main treatment for Parkinson’s motor symptoms.

Per the companies’ previous agreement, Prothena will receive a $60 million clinical milestone payment from Roche when the first patient is dosed in the new trial.