RARE Daily

FDA Lifts Clinical Hold on Inhibikase Therapeutics Therapy for Multiple System Atrophy

March 8, 2023

Rare Daily Staff

The U.S. Food and Drug Administration lifted the full clinical hold on Inhibikase Therapeutics experimental therapy IkT-148009 for the treatment of multiple system atrophy clearing the way for a phase 2 clinical trial.

Multiple System Atrophy (MSA) is a rapidly progressive rare disease affecting the central and autonomic nervous systems. MSA is characterized by pathological alpha-synuclein aggregation, which may lead to cell dysfunction and degeneration of neurons. MSA affects men and women equally, with onset of symptoms typically occurring in the fifth or sixth decade of life. Rapid progression of the disease results in patients becoming wheelchair bound in many cases, with varying combinations of extrapyramidal dysfunction, cerebellar ataxia, dysautonomia and parkinsonism. Currently, no disease-modifying or symptomatic therapies exist for the condition.

IkT-148009 is a potent, selective, brain penetrant c-Abl tyrosine kinase inhibitor that has been shown to halt disease progression, protect and restore lost neurons and clear the underlying protein pathology in animal studies of Parkinson’s disease. In previously published work, Inhibikase has demonstrated that MSA may also be initiated by c-Abl modification of alpha-synuclein aggregates in the brain. In ongoing animal models of MSA, Inhibikase has observed that IkT-148009 shows a substantial neuroprotective benefit, preventing functional loss in mice following 7 week, once-daily dosing.

Inhibikase said it will continue to evaluate the functional benefit of IkT-148009 for an additional three months to assess whether IkT-148009 leads to clearance of alpha-synuclein aggregate pathology in the treated animals.

The planned trial will evaluate the safety, tolerability and pharmacokinetics of IkT-148009 in MSA patients over six months of once daily dosing at one of two oral doses. Secondary and exploratory endpoints will evaluate clinical benefit using a modification of the Total Unified MSA Rating Scale, an assessment of quality of life. Severity of symptoms arising from orthostatic hypotension, and the levels of neurofilament light chain in peripheral blood and spinal fluid. Additionally, biomarkers of treatment benefit will be explored by measuring levels of phosphorylated alpha-synuclein in spinal fluid, peripheral blood and skin. Clinical effect on the progression of atrophy will be monitored in the trial using MRI.

“As with our work in Parkinson’s, preclinical models have highlighted the therapeutic potential of IkT-148009 in MSA,” said Milton Werner, president and CEO of Inhibikase Therapeutics. “One of two ongoing model studies has shown a substantial neuroprotective benefit in response to c-Abl inhibition by IkT-148009. With the clinical hold lifted and the IND now open, we look forward to completing these studies prior to initiation of the phase 2a trial in this patient population.”

Photo: Milton Werner, president and CEO of Inhibikase Therapeutics

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