Verdiperstat Aims to Be First DMT for Multiple System Atrophy

NeurologyLiveJune 2020
Volume 3
Issue 3

Biohaven’s verdiperstat has entered a phase 3 trial for the treatment of multiple system atrophy, with a new drug application submission on the agenda for late 2021.

Irfan Qureshi, MD

Irfan Qureshi, MD

Verdiperstat (Biohaven), a first-in-class, potent, selective, brain-penetrant, irreversible myeloperoxidase (MPO) enzyme inhibitor is the subject of the phase 3 M-STAR clinical trial (NCT03952806) for the treatment of patients with multiple system atrophy (MSA).1 The randomized, double-blind, placebo-controlled, parallel group study began enrollment in July 2019 and is expected to reach its estimated total enrollment of 250 subjects, age 40 to 80 years, by the fourth quarter of 2020, with a primary study completion date of October 2021 (FIGURE).1

Verdiperstat is a unique orally administered MPO inhibitor. The MPO enzyme acts as a key driver of oxidative stress and inflammation that underlies neurodegeneration and is abundant in activated microglial cells found in the brains of patients with MSA.

“The goal of the M-STAR study is to determine whether verdiperstat can reduce MSA disease progression, for both subtypes of MSA: parkinsonism and cerebellar. The primary efficacy end point is the change from baseline to week 48 in verdiperstat- versus placebo-treated subjects on a modified UMSARS [Unified MSA Rating Scale] score, which consists of a subset of items from the UMSARS Part I (Activities of Daily Living) and Part II (Motor Exam) that directly assess clinically meaningful change in patients’ ability to function,” Irfan Qureshi, MD, vice president of neurology at Biohaven, told NeurologyLive®.

Patients eligible for inclusion in the trial must have a diagnosis of probable or possible MSA, be able to ambulate without the assistance of another individual, and have an anticipated survival of at least 3 years at the time of screening. Those who have any neurological disorders other than MSA or any condition that may interfere with the subject’s ability to adhere to study instructions are excluded from the study. Secondary outcome measures include change from baseline to week 48 on Clinical Global Impression of Improvement score as well as impact of verdiperstat on quality of life, measured by a change from baseline in the motor and nonmotor subscales of the MSA Quality of Life scale at week 48.

The history of verdiperstat has been well documented with the FDA as it has climbed through the clinical pipeline. In February 2019, the agent received orphan drug designation after completing its phase 1 and 2a clinical trials.2

The 12-week, randomized, double-blind, placebo-controlled phase 2a study (NCT02388295) was designed to evaluate the safety and tolerability of 2 doses of verdiperstat in patients with MSA. Fifty-nine patients were randomly assigned to receive either verdiperstat 300 mg or 600 mg twice daily (n = 19, n = 20, respectively) or placebo (n = 20).2

Results indicated that the drug significantly decreased MPO activity in plasma, with favorable trends over 12 weeks on UMSARS. Over the treatment period, patients in the placebo group experienced greater worsening on the UMSARS, with a 4.6-point decline (standard error [SE], 1.1; 90% CI, 2.5-6.8) compared with 3.7- (SE, 1.2; 90% CI, 1.4-5.7) and 2.6-point (SE, 1.4; 90% CI, 0.5-4.7) declines in patients treated with verdiperstat 300 mg or 600 mg, respectively.2 The investigators also noted positive effects on outcome measures, such as the Composite Autonomic Symptom Score and MSA Quality of Life scale.2

This past March, the FDA granted the drug fast track designation for the treatment of MSA.3

“Biohaven sees the potential for verdiperstat to be the first disease-modifying treatment for MSA. No disease-modifying treatments currently exist for MSA; only symptomatic and palliative therapies are available,” Qureshi said.

Biohaven is expected to submit a new drug application to the FDA in late 2021 or early 2022 if the M-STAR study demonstrates that verdiperstat is effective against MSA.


1. Biohaven enrolls first patient in phase 3 clinical trial of verdiperstat, oral myeloperoxidase inhibitor, for the treatment of multiple system atrophy. News release. Biohaven Pharmaceutical. July 31, 2019. Accessed May 6, 2020.

2. Biohaven’s verdiperstat receives orphan drug designation from FDA for multiple system atrophy. News release. Biohaven Pharmaceutical. February 19, 2019. Accessed May 6, 2020.

3. Biohaven’s verdiperstat receives fast track designation for the treatment of multiple system atrophy. News release. Biohaven Pharmaceutical. March 18, 2020. Accessed May 6, 2020.

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