Failed studies prompt Lundbeck to terminate foliglurax in Parkinson's disease, Lu AG06466 in Tourette syndrome

Lundbeck reported Friday that it is ending development of foliglurax in Parkinson's disease and Lu AG06466 in adults with Tourette syndrome after the experimental drugs failed their respective Phase IIa studies. Commenting on foliglurax, which was being assessed in the AMBLED trial, Lundbeck's R&D chief Johan Luthman said the company was "disappointed" that the drug did not demonstrate sufficient efficacy for patients with Parkinson's disease, but that it has decided to "focus…resources on more promising programmes."

However, in regards to Lu AG06466, Lundbeck noted that "while there was insufficient efficacy to proceed with development of Lu AG06466 in Tourette syndrome, the safety and tolerability of the agent was such that further investigational studies in additional indications will proceed." 

The AMBLED study involved 157 patients diagnosed with idiopathic Parkinson's disease for at least three years, who were being treated with a stable regimen of levodopa-based therapy and experiencing OFF time and dyskinesia. Participants were randomised to receive either one of two doses of foliglurax twice daily as an adjunct to levodopa for a 28-day treatment period. The primary endpoint was change from baseline in the daily awake OFF time, based on subject Hauser diary entries, while dyskinesia was assessed as a secondary goal in terms of change from baseline in the Unified Dyskinesia Ratings Scale (UDysRS) score.

Lundbeck said there was no statistically significant difference on the primary endpoint, with the difference in change from baseline being 0.27h and 0.44h for the low and high foliglurax doses, respectively, versus placebo. Similarly, neither of the doses separated from placebo on the secondary dyskinesia goal either.

Lundbeck acquired foliglurax, also known as Lu AF99757, which works by stimulating the glutamatergic target mGluR4, following its acquisition of Prexton Therapeutics in 2018 in a deal worth up to €900 million ($1 billion). The Danish drugmaker is conducting additional analyses "to understand the totality of the foliglurax data," adding that the AMBLED results will be published "in the near future."

Meanwhile, the randomised study of Lu AG06466 in Tourette syndrome enrolled 48 patients. According to Lundbeck, findings indicate that the primary endpoint, measured on the Yale Global Tic Severity Scale (YGTSS-TTS), was not met compared to placebo after 28 and 56 days of treatment. However, the drugmaker noted that the MAGL inhibitor, which also acts as a selective modulator of the endocannabinoid system, did not show any adverse events that would barr it from being developed for something else, adding that it plans to conduct studies of Lu AG06466 in other indications in neurology and psychiatry.

Luthman said "further exploration both of this molecule and the endocannabinoid biology will continue," and indicated that Lundbeck is looking "to develop multiple new classes of drugs for a broad spectrum of brain diseases and harnessing the therapeutic potential of one of the largest and most diverse enzyme classes – the serine hydrolases."

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