FDA Lifts Partial Clinical Hold on Vigil’s Study of TREM2 Candidate for the Treatment of ALSP

Rare Daily Staff

The U.S. Food and Drug Administration lifted its partial clinical hold Vigil Neuroscience’s clinical trial evaluating its TREM2 candidate VGL101 for the treatment of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, or ALSP.

The hold had been on doses greater than 20 mg/kg for VGL101 in its ongoing and future clinical trials in patients with ALSP. VGL101, Vigil’s lead product candidate, is currently being studied in IGNITE, a phase 2 proof-of-concept trial in patients with ALSP as well as in an ongoing phase 1 single and multiple ascending dose (SAD and MAD) healthy volunteer trial.

“We are happy to share that the FDA has lifted the partial clinical hold on VGL101 based on supporting clinical data from our ongoing phase 1 trial,” said Ivana Magovčević-Liebisch, president and CEO of Vigil. “Although we believe that 20 mg/kg is a clinically relevant dose in ALSP, we are very pleased that the hold has been lifted as we believe it’s important to maintain optionality to develop treatments that support patients suffering from both rare and common neurodegenerative indications.”

ALSP is a rare, inherited, autosomal dominant neurological disease with high penetrance. It is caused by a mutation to the CSF1R gene and affects an estimated 10,000 people in the United States, with similar prevalence in Europe and Japan. The disease generally presents itself in adults in their forties, is diagnosed through genetic testing and established clinical/radiologic criteria and is characterized by cognitive dysfunction, neuropsychiatric symptoms, and motor impairment. These symptoms typically exhibit rapid progression with a life expectancy of approximately six to seven years on average after diagnosis, causing significant patient and caregiver burden. There are currently no approved therapies for the treatment of ALSP, underlining the high unmet need in this rare indication.

VGL101, Vigil’s lead product candidate, is a fully human monoclonal antibody targeting human triggering receptor expressed on myeloid cells 2 (TREM2), which is responsible for maintaining microglial cell function. TREM2 deficiency is believed to be a driver of certain neurodegenerative diseases. VGL101 is in development for rare microgliopathies, such as ALSP, as well as other neurodegenerative diseases for which TREM2 and/or microglia deficiency is believed to be a key driver of disease pathway.

In November 2022, Vigil reported interim top-line data from the phase 1 trial in healthy volunteers in the United States and Australia. Based on these data, VGL101 demonstrated favorable safety and tolerability profiles at doses up to 40 mg/kg SAD and 20 mg/kg MAD. The company expects to report the full data analysis up to 60 mg/kg from the phase 1 trial in the second half of 2023.

In December 2022, Vigil initiated a phase 2 proof-of-concept clinical trial evaluating VGL101 in patients with ALSP. IGNITE, the first interventional trial in ALSP, is a global phase 2, open-label trial designed to evaluate the safety and tolerability of VGL101 in up to 15 patients with symptomatic ALSP who have a CSF1R gene mutation. Patients enrolled in the trial will receive an intravenous infusion of 20 mg/kg of VGL101 approximately every 4 weeks for a treatment duration of one year. Vigil expects to report six-month interim data from the first six patients in this trial in the second half of 2023.

The FDA previously granted Fast Track and Orphan Drug designations to VGL101 for the treatment of ALSP.

Photo: Ivana Magovčević-Liebisch, president and CEO of Vigil