LRRK2 Therapy Reports Positive Phase I Findings
Tuesday, 11th May 2021

A drug to lower activity of the protein LRRK2 — which is higher in some people with Parkinson’s — will move into a later-stage trial this year after positive results.

In early May Denali Therapeutics and Biogen announced final data from their Phase I trials of BIIB122/DNL151. The drug was safe in control volunteers and people with Parkinson’s. It also impacted measures of LRRK2 activity, showing that BIIB122/DNL151 is changing biology as intended.

Last summer Denali and pharmaceutical company Biogen announced a partnership to advance Denali’s LRRK2 drugs and a plan to move BIIB122/DNL151 into later-stage development in 2021. (Biogen is additionally testing another therapeutic approach to lower LRRK2 levels.)

“This new data shows safety and biological impact with different doses of the drug,” said Marco Baptista, PhD, Vice President of Research Programs at The Michael J. Fox Foundation who has led our LRRK2 portfolio for nearly a decade. “Denali and Biogen now have the information that will help them pick the doses for their next trials that will hopefully be safe and may be successful in slowing disease. This is an exciting step.”

The data comes from a Phase I study of control volunteers and a Phase Ib study of people with Parkinson’s disease (PD). Some had LRRK2 mutations, and some had idiopathic PD (cause unknown). LRRK2 mutations increase protein activity, and MJFF-funded research has found people with idiopathic PD can have the same. So, Denali and Biogen are testing their drug in both groups.

No one in the studies experienced serious adverse events. A few participants reported nausea, headache or dizziness.

And the study’s tests showed that the drug normalized levels of a form of LRRK2 protein and of a substrate of LRRK2 (a protein modified by LRRK2). This means this treatment could correct this imbalance that may play a role in PD onset and progression.

Additionally, BIIB122/DNL151 reduced levels of a marker called BMP. This marker of LRRK2 cellular function, linked to PD by Baptista and partners, is higher in people with LRRK2 mutations. These results are another piece of evidence that this therapy may be helping cells operate better.

The next trial is expected to begin in late 2021. That study will review safety and explore therapeutic impact on both biology and clinical symptoms in more people with Parkinson’s (with a LRRK2 mutation or idiopathic PD).

Rick Grant, 57, from Bel Air, Maryland is following this news closely. He carries a LRRK2 mutation and participated in a trial for another LRRK2 drug from Denali: DNL201. (That drug also showed positive results, but the partners chose DNL151 to move forward.)

“If we can strike Parkinson’s out right now — if my children don’t have to have it or my grandchildren don’t have to have it, if we make one person better — we’ve done our job,” he said.

Shake It Up Australia together with our partners at The Michael J. Fox Foundation have been funding LRKK2 Research project in Australia.

Learn more about LRRK2