Roche Phase IIb study of prasinezumab did not measure primary endpoint, but suggests possible benefit in early-stage Parkinson’s

PADOVA showed numerical delayed motor progression and positive trends for several secondary and exploratory endpoints
Prazinezumab continues to be well tolerated and no new safety features have been observed
Roche continues to evaluate the data and will work with public health authorities to determine next steps

Basel, December 19, 2024. – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from the Phase IIb PADOVA study, which investigated prasinezumab in 586 people with early-stage Parkinson’s disease who had been treated for at least 18 months with stable symptoms. Prasinezumab demonstrated potential clinical efficacy in the primary endpoint of time to confirmed motor progression with HR=0.84 (0.69-1.01) and p=0.0657, without statistical significance. In the prespecified analysis, the effect of prazinezumab was more pronounced in the levodopa-treated population (75% of participants), HR=0.79 (0.63-0.99). Sustained positive trends were also observed in several secondary and exploratory endpoints. Prazinezumab continues to be well tolerated and no new safety signals were observed in the study.

“Parkinson’s disease is challenging and devastating because there are no disease-modifying treatment options for millions of sufferers,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “We believe the continued efficacy trends from the phase IIb trial of prasinezumab merit further study. We will continue to work closely with the Parkinson’s community as we further evaluate the data to determine next steps.”

The extended open-label phase II PASADENA and phase IIb PADOVA studies will be continued to examine 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 an upcoming medical meeting.

About prazinezumab
Prasinezumab is an investigational monoclonal antibody designed to selectively bind aggregated a-syn and reduce neuronal toxicity. By targeting the accumulation of a-syn protein in the brain, prazinezumab could potentially prevent further accumulation and spread between cells, thereby slowing disease progression. The evidence supporting targeting α-syn aggregates as a mechanism of action in Parkinson’s disease is based on a wide range of scientific evidence in the field.

Prasinezumab is currently being evaluated in the ongoing open-label phase II PASADENA and phase IIb PADOVA extensions. Four-year data from the PASADENA study showed potential evidence of sustained slowing of motor progression compared with a matched cohort from the PPMI Nature Study, published in the October 2024 issue of Nature Medicine. The PASADENA delayed-onset (n?=?94) and early-onset (n?=?177) groups showed a slower decline (smaller increase in scores) in MDS–UPDRS Part?III scores in the OFF (delayed-onset) condition, -51%; early start, -65%) than external PPMI comparator (n?=?303). The safety database for prazinezumab consists of data from more than 900 Parkinson’s study participants who received the study drug, including more than 500 who were treated for 1.5 to 5 years.

In December 2013, Roche entered into a licensing, development and commercialization agreement with Prothena to develop and commercialize monoclonal antibodies against a-syn, such as prazinezumab, for the treatment of Parkinson’s disease.

About the PADOVA study
PADOVA is a multicenter, randomized, double-blind, phase IIb study evaluating the efficacy and safety of prazinezumab versus placebo in 586 randomized patients with early Parkinson’s disease receiving stable symptomatic treatment (stable doses of levodopa or monoamine oxidase B inhibitor). as monotherapy for more than three months initially). Patients receive monthly intravenous doses of prazinezumab 1500 mg or placebo every four weeks for at least 76 weeks. This is followed by a two-year open-label extension phase in which all participants receive active treatment, which is currently ongoing.

The primary PADOVA endpoint is time to confirmed motor progression of Parkinson’s disease (= a 5-point increase in Movement Disorders Society Parkinson’s Movement Disorders Rating Scale (MDS-UPDRS) Part III scores assessed in the treatment OFF condition). An increase of 5 points in the MDS-UPDRS Part III represents a clinically significant motor progression event (Trundell et al., in press).

About Parkinson’s disease
Parkinson’s disease is a chronic, progressive, and debilitating neurodegenerative disease characterized by the gradual loss of dopamine-producing neurons and other nerve cells, and the development of motor and non-motor symptoms that may appear years before diagnosis. Today, heart disease affects more than 10 million people worldwide. The prevalence of Parkinson’s disease is increasing, and it has become one of the fastest growing neurological disorders. Currently, symptomatic treatment methods are available that effectively relieve motor symptoms, which significantly affects people’s quality of life; however, no available symptomatic therapy can slow or stop the clinical progression of Parkinson’s disease, and the effects disappear over time as the disease progresses.

Roche is evaluating multiple approaches to slowing disease progression and potentially preventing Parkinson’s disease that involve targeting processes underlying the disease, such as aggregated α-syn production, lysosomal dysfunction, and neuroinflammation.

About Roche in Neuroscience
Neurology is the main area of research and development of the Roche company. Our goal is to advance groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating illnesses.

Roche is investigating more than a dozen drugs for neurological disorders, including neuromuscular diseases: Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy and spinal muscular atrophy; neuroimmune diseases: multiple sclerosis and neuromyelitis, visual spectrum disorder; and neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Together with our partners, we strive to push the boundaries of scientific understanding to solve some of the most challenging challenges in neuroscience today.

About Roche

Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded drugs, Roche has grown into the world’s largest biotechnology company and a world leader in in vitro diagnostics. The company is committed to scientific excellence to discover and develop medicines and diagnostics to improve and save lives around the world. We are pioneers in the field of personalized healthcare and want to further transform the way healthcare is delivered to have an even greater impact. To provide the best care for each individual, we collaborate with many stakeholders and combine our strengths in diagnostics and pharmacology with evidence from clinical practice.

For more than 125 years, sustainability has been an integral part of Roche’s business. As a scientific company, our greatest contribution to society is the development of innovative medicines and diagnostics that help people live healthier lives. Roche is committed to achieving net zero by 2045 through its Science-Based Targets and Sustainable Markets Initiative.

Genentech in the United States is a 100 percent Roche Group company. Roche is the majority shareholder of Chugai Pharmaceutical, Japan.

For more information visit www.roche.com.

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