New Parkinson’s drugs targeting apathy, falls, are advancing
Irlab launching trial of IRL757, says pirepemat reduces fall rate by 50%
Irlab Therapeutics has announced new advancements for its three symptoms-targeting Parkinson’s disease drugs — medications designed to treat apathy, prevent falls, and reduce uncontrolled movements, known as dyskinesia, among people with the neurodegenerative disease.
Before the year’s end, the company intends to launch a Phase 1b clinical trial testing its IRL757 oral tablets for treating apathy, or a loss of motivation, in people with Parkinson’s. Irlab has received $4 million in funding from a partner for this study, the company stated in its latest interim report, covering the period from January through September.
The developer also shared new data showing that pirepemat, its oral medication for preventing falls in people with Parkinson’s, was shown to significantly reduce fall risk after three months in a clinical trial.
Additionally, Irlab has been granted a new patent in China for mesdopetam, its therapy for levodopa-induced dyskinesia. That patent will provide market exclusivity for the oral treatment in the country into the mid-2040s, Irlab said.
“We have taken several important steps in the development of our leading drug projects,” said Kristina Torfgård, PhD, CEO of Irlab, adding that, following this progress, “the management team now continues to execute our strategy with full focus and determination.”
Parkinson’s is caused by the progressive loss of nerve cells in the brain that are responsible for making dopamine. Dopamine is a signaling molecule that nerve cells use to communicate with each other and the rest of the body.
The loss of dopamine-making cells causes problems with nerve signaling, ultimately giving rise to a range of motor symptoms, including slowed movements and gait and balance issues, as well as nonmotor symptoms such as mood and cognitive changes, which can include increased apathy.
Apathy affects up to 70% of Parkinson’s patients
IRL757 is an oral medication designed to treat apathy, which affects as many as 70% of people with Parkinson’s, according to Irlab.
The therapy is thought to restore communication between the cerebral cortex — the outermost layer of the brain — and deeper brain regions. Disruption of this communication is a proposed mechanism underlying apathy in neurological disorders, and preclinical studies have suggested the drug can improve motivation.
Thus far, the treatment candidate has been tested in two Phase 1 clinical trials. In a first-in-human trial (NCT06493045), 82 healthy volunteers received single or multiple ascending doses of IRL757 or a placebo. A second trial (NCT06699628) tested the medication in 12 healthy elderly volunteers, ages 65 to 89.
Results from both studies showed that IRL757 is well absorbed, leading to good exposure to the medication. The data also demonstrated that the therapy had a favorable tolerability and safety profile.
Now, Irlab is planning to launch a Phase 1b clinical trial that will test whether IRL757 can reduce apathy in people with Parkinson’s disease. The trial will be fully funded by the McQuade Center for Strategic Research and Development (MSRD), Irlab’s partner, and recruitment is expected to begin before the end of the year, per the company. MSRD has made payment of the $4 million in funding, per Irlab.
“We are excited about the potential of our drug candidate IRL757, now moving rapidly [toward] a clinical study aiming to detect early signals of efficacy in Parkinson’s patients experiencing apathy,” Torfgård said in another company press release. “Scientific and financial support from our collaborator MSRD allows us to efficiently advance the development of this first-in-class drug candidate.”
Parkinson’s drug pirepemat found to lower fall rate
Pirepemat is another medication being developed by Irlab for people with Parkinson’s — one that aims to prevent falls among patients, a common issue. It works by targeting receptors in the prefrontal cortex and strengthening nerve cell signaling.
An in-depth analysis of data from the Phase 2b REACT-PD trial (NCT05258071) demonstrated that pirepemat reduced fall rates by as much as 51.5% after three months of treatment — an effect that was clinically meaningful and statistically significant. This was observed with a median exposure of the drug; no significant benefits were seen at high or low treatment doses.
“It is clear to us that there is a way forward for pirepemat to address the largest unmet need in the treatment of Parkinson’s disease,” Torfgård said in another press release announcing those results.
Joakim Tedroff, MD, PhD, chief medical officer at Irlab, said the results demonstrate that the therapy “affects the brain mechanisms involved in the systems controlling upright posture and stability leading to reduced fall rate.”
“It is very encouraging that we now have gained a deeper understanding of the exposure dependent efficacy profile of our drug candidate,” Tedroff said.
It is clear to us that there is a way forward for pirepemat to address the largest unmet need in the treatment of Parkinson’s disease.
This year, the company also received a new patent protection for mesdopetam, its experimental treatment for people with Parkinson’s who develop levodopa-induced dyskinesia. Mesdopetam works by blocking the activity of a dopamine receptor called D3.
While levodopa — a standard Parkinson’s treatment that provides the raw materials for cells to make dopamine — is effective at easing the disease’s motor symptoms, its long-term use frequently leads to dyskinesia.
“The already strong patent protection for mesdopetam in China is now being extended to include the salt form of the active ingredient used in the clinical development,” Torfgård said in a press release from earlier this year announcing the new patent. “This extended protection can potentially extend the market exclusivity of mesdopetam [toward] the mid 2040s.”
In a Phase 2b clinical trial (NCT04435431), the highest dose of mesopetam was shown to ease levodopa-induced dyskinesia compared with a placebo. It also reduced off periods, when symptoms are not well controlled between doses.
After completing the trial, Irlab said it was planning to move into a Phase 3 trial to further test the efficacy of mesdopetam at easing dyskinesia. According to the company, the treatment also has potential to treat Parkinson’s disease psychosis, or the loss of contact with reality.
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