The drug candidate mesdopetam is in development for the treatment of dyskinesia, i.e. involuntary movements (LIDs), associated with Parkinson’s disease (PD). LIDs occur as a side effect from long-term use of levodopa, the standard treatment in PD, and remains an unmet medical need since the introduction of levodopa in the 1970s. Mesdopetam has also shown antipsychotic properties and will be further investigated in PD psychosis (PD-P). Mesdopetam is in clinical phase II and in development with partner Ipsen who has exclusive global rights for development and commercialization.
Mesdopetam is intended as a supplementary medicine for patients with Parkinson’s disease, to be used in combination with the standard levodopa treatment. Through decrease of dyskinesia, mesdopetam is aimed to increase the daily time when levodopa treatment works well without the patient experiencing troublesome dyskinesia, so called “good ON-time”. Troublesome side effects in the form of excessive involuntary movements (dyskinesia, LIDs) arise in approximately 30% of patients after 5 years of treatment with levodopa, and as many as about 60% after 10 years of treatment. Many patients also suffer from psychiatric illness in the form of hallucinations (PD-Psychosis or PD-P), which set in during the course of the disease.
Today, patients affected by levodopa induced dyskinesia (LIDs) have few treatment alternatives available and none with a similar potential as mesdopetam to improve patients’ quality of life by addressing both motor and mental complications.
Mesdopetam is a dopamine D3 receptor antagonist
Mesdopetam acts by antagonizing the dopamine D3 receptor and thereby counteracting the physiological effects of the signal substance dopamine. The dopamine D3 receptor is genetically linked to increased risk of involuntary movements and patients with PD-LIDs have higher amounts of D3 receptors in parts of the brain essential for the control of movements.
Clinical phase results
Mesdopetam has successfully gone through clinical studies demonstrating a good safety and tolerability profile. In 2019, a 28-Day Phase IIa study was concluded evaluating the effect and tolerability of mesdopetam in PD patients exhibiting LIDs.
The study results show clinically meaningful and quantitatively impressive effects on dyskinesias as assessed by two of the most used measurements in the field: standardized patient-reported diaries (Hauser diaries) and the Unified Parkinson’s Disease Rating Scale (UPDRS). Patients reported marked improvements without added side effects, demonstrating mesdopetam’s ability to offer a significant qualitative shift in patients’ everyday life.
Mesdopetam is aimed to improve patients’ quality of life by increasing the daily time when levodopa treatment works well without troublesome dyskinesias, so called “good ON-time”. This is achieved through specifically targeting the cause of dyskinesias.
Ongoing clinical phase IIb/III study
A larger and longer Phase IIb/III study to further evaluate the effects of mesdopetam in PD-LIDs started in November 2020. The clinical phase IIb/III study with mesdopetam is a randomized, double-blind and placebo-controlled study with the aim of evaluating the effect of mesdopetam in patients with Parkinson’s disease affected by troublesome dyskinesias.
The primary outcome measure is change in daily hours of ON-time without troublesome dyskinesia as assessed with 24-hour patient home diaries. The study is designed to randomize approximately 140 patients distributed across four groups, three dose levels of mesdopetam and a placebo group with approximately 35 patients in each group. Each patient will have a three-month treatment period. The study is planned to include patients in USA and Europe.
A Phase II study in PD-Psychosis is planned to follow.
About the recommended INN, mesdopetam
Since early 2020, IRL790 goes by the International Nonproprietary Name (INN), mesdopetam. The World Health Organization (WHO) concluded that IRL790 is unique in its mechanism of action and assigned a new INN, mesdopetam, that can become a new substance class in the existing classification system for pharmaceutical substances. The INN will serve to identify the active pharmaceutical substance of mesdopetam during its lifetime worldwide.
Solid intellectual property rights
Mesdopetam has an approved substance patent in all major markets worldwide. The patent application was submitted in 2012 and provides protection for at least 20 years. Provided the regulatory requirements are met, the patent protection can be extended at most until 2037 in the US, Europe and Japan.
Mesdopetam will enjoy market exclusivity as a new chemical compound, for ten years from market approval in Europe and five years from market approval in the US.
Ready for large-scale manufacture
In parallel with clinical development, manufacturing methods for production of the active substance (API) and drug product (DP) have been optimized for mesdopetam and analytical methods needed for quality control of the API and DP have been further developed. The purpose is to prepare for future clinical studies in accordance with regulatory requirements and guidelines.