Roche’s phase IIb study of bracinizumab misses its primary endpoint, but suggests potential clinical benefit in early-stage Parkinson’s disease.

• The PADOVA study demonstrated a numerical delay in motor progression and positive trends on multiple secondary and exploratory endpoints
• Brasnezumab continues to be well tolerated and no new safety signals have been observed
• Roche is evaluating the data further and will work with health authorities to determine next steps

DUBLIN–( BUSINESS WIRE )– Prothena Corporation plc (NASDAQ:PRTA) today announced results from its partner Roche’s Phase IIb PADOVA study, which investigated bracinizumab in 586 people. People with early-stage Parkinson’s disease who have been treated for at least 18 months. During treatment of stable symptoms. Brasnezumab showed a potential clinical effect in the primary endpoint of time to confirmed motor progression with HR = 0.84 (0.69-1.01) and p = 0.0657. The effect of bracinizumab was more pronounced in a prespecified analysis in the levodopa-treated population (75% of participants), HR = 0.79 (0.63-0.99), p = 0.0431. Prespecified covariate-adjusted supplementary analyzes of these endpoints showed nominally significant effects on the primary endpoint (HR = 0.81 (0.67-0.98); nominal p = 0.0334) and in the levodopa subgroup (HR = 0.76 (0.61-0.95); nominal p = 0.0175). Consistent positive trends were also observed across multiple secondary and exploratory endpoints. Brasnezumab remains well tolerated and no new safety signals were observed in the study.

The results of Phase IIb PADOVA combined with the results of previous clinical studies will aid future clinical development, including study design, statistical analysis and appropriate evaluation of patient subgroups, of bracinizumab as a potential first-line disease-modifying treatment for patients with Parkinson’s disease.

“The results of the Phase 2b PADOVA study are an important step forward for potentially offering the first disease-modifying treatment option to millions of individuals with Parkinson’s disease and their families,” said Gene Kenny, Ph.D., President and CEO. , prothena. As leaders in the development of the first antibody targeting anti-alpha synuclein, we look forward to Roche presenting the results of the PADOVA study at an upcoming medical conference and sharing them with health authorities to determine the most appropriate path forward.

Open-label extension studies of Phase II PASADENA and Phase IIb PADOVA will continue in order to explore the effects observed in both studies. Roche will continue to evaluate the data and work with health authorities to determine next steps.

The full results of the PADOVA study will be presented at the next medical meeting.

About bracinizumab

Brasinizumab is a monoclonal antibody designed to selectively bind aggregated α-syn and reduce neuronal toxicity. By targeting the accumulation of α-syn protein in the brain, pracinizumab can prevent further accumulation and spread between cells, thus slowing the progression of the disease. The evidence supporting targeting α-syn as a mechanism of action in Parkinson’s disease is based on a wide range of scientific evidence in this area.

Brasnezumab is currently being evaluated in ongoing open-label extensions of Phase II Pasadena and Phase IIb Padova studies. Published in the October 2024 edition of Nature Medicine, four years of data from the PASADENA study showed potential evidence of a persistent slowing of motor progression compared with the matched PPMI natural history study group. The PASADENA late onset (n = 94) and early onset (n = 177) groups showed a slower decline (smaller score increase) in MDS’ UPDRS Part III scores in the OFF condition (late onset, ˆ’51%); early onset, ˆ ‘65% of what the PPMI external comparison did (n = 303). The brasenizumab safety database consists of data from more than 900 Parkinson’s disease study participants who They were treated with experimental medicine, including more than 500 treated over 1.5-5 years.

Roche entered into a license, development and commercialization agreement with Prothena in December 2013 to develop and commercialize monoclonal antibodies targeting α-syn, such as brasenizumab, for the potential treatment of Parkinson’s disease.

About the study of Padua

PADOVA is a randomized, double-blind, multicenter, phase IIb trial evaluating the efficacy and safety of bracinizumab compared with placebo in 586 randomized patients with early-stage Parkinson’s disease who were receiving stable symptomatic treatment (fixed doses of levodopa or a monoamine oxidase-B inhibitor). . As monotherapy for more than three months at baseline). Patients receive monthly doses of bracinizumab 1,500 mg or placebo every four weeks for at least 76 weeks. This is followed by a two-year open-ended extension phase in which all participants receive active treatment, which is currently ongoing.

The primary endpoint of PADOVA is time to confirmation of motor progression of Parkinson’s disease (an increase of ‰¥5 points in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III assessed if the drug is discontinued). A 5-point increase in the MDS-UPDRS Part III represents a clinically meaningful event of motor progression (Trundell et al., in press).

About Parkinson’s disease

Parkinson’s disease is a chronic, progressive, and debilitating neurodegenerative disease that has a devastating impact on patients and their families. Parkinson’s disease is characterized by the progressive loss of neurons that make dopamine and other neurons, and the development of motor and non-motor symptoms that may appear years before diagnosis. Symptoms can vary greatly between individuals and the progression of the disease is unpredictable, as symptoms can develop gradually over time or suddenly. Clinical diagnosis of Parkinson’s disease is late in the disease course and is currently based only on motor symptoms, and non-motor symptoms often precede diagnosis by up to 20 years.

About Prothena

Prothena Corporation plc is a late-stage clinical biotechnology company with expertise in protein dysregulation and a pipeline of investigational therapeutics with the potential to alter the course of devastating neurodegeneration and rare peripheral amyloid diseases. Backed by deep scientific expertise built on decades of research, Prothena is developing a pipeline of therapeutic candidates for a number of novel indications and targets that will leverage its ability to integrate scientific insights into neuronal dysfunction and the biology of misfolded proteins. Prothena’s pipeline includes both wholly owned and partnered programs being developed for the potential treatment of diseases including AL amyloidosis, ATTR amyloidosis with cardiomyopathy, Alzheimer’s disease, Parkinson’s disease and a number of other neurodegenerative diseases. For more information, please visit the company’s website at www.prothena.com and follow the company on Twitter @ProthenaCorp.

Forward-looking statements

This press release contains forward-looking statements. These data relate to, among other things, the treatment potential, design, and proposed mechanism of action of pracinizumab; Plans for ongoing and future clinical trials of bracinizumab; It plans to work with health authorities to determine next steps for the use of bracinizumab; and expected reporting data from PADOVA clinical trials. These statements are based on estimates, forecasts and assumptions that may prove to be inaccurate, and actual results may differ materially from those anticipated due to known and unknown risks, uncertainties and other factors, including but not limited to those described in Risk Factors. Sections of our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 12, 2024, and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with Sec. We undertake no obligation to publicly update any forward-looking statements contained in this press release as a result of new information, future events or changes in our expectations.

Covariates used for adjustment: medication at baseline, H&Y stage, DaT-SPECT, age, sex, baseline-dependent parameter.

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Source: Prothena plc