Add-on NE3107, now bezisterim, eases Parkinson’s symptoms

Treatment lessened motor, nonmotor symptoms, trial data show

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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NE3107, now known as bezisterim, eased both motor and nonmotor symptoms when used in combination with a standard carbidopa/levodopa regimen in people with Parkinson’s disease, study data showed.

Twice-daily dosing with the anti-inflammatory small molecule being developed by BioVie resulted in better motor function upon waking, more restful sleep, and less urge to move the legs compared with a placebo, according to full data from a Phase 2a study (NCT05083260)

“Bezisterim as adjunct therapy to levodopa may hold promise in ameliorating specific non-motor symptoms of Parkinson’s [disease], particularly in sleep/fatigue and restlessness of the legs,” Joseph Palumbo, MD, BioVie’s chief medical officer, said in a company press release.

The data were shared in an oral presentation, “Improvement of Motor and Non-Motor Symptoms with Bezisterim Adjunctive to Carbidopa/Levodopa in Patients with Parkinson’s Disease: A Phase 2A, Placebo-Controlled Study,” at the XXIX World Congress on Parkinson’s Disease and Related Disorders, held May 19–22 in Lisbon, Portugal.

Parkinson’s motor symptoms occur when dopaminergic neurons in the brain gradually stop working and die. Dopaminergic neurons are nerve cells that produce dopamine, a chemical in the brain that is involved in the control of body movement.

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In addition to motor symptoms such as slowness of movement, tremor, stiffness, and difficulty with balance, many patients experience nonmotor symptoms. These include trouble falling or staying asleep, tiredness or sleepiness during the day, and restless legs.

Although the exact causes of Parkinson’s are unclear, there is evidence that neuroinflammation plays a role. In Parkinson’s, an uncontrolled inflammatory response may act on healthy tissue in the brain, causing dopaminergic neurons and other cells of the nervous system to become damaged and die.

Bezisterim, is an oral small molecule designed to reach the brain and keep the inflammatory response under control. It also inhibits insulin resistance, in which response to insulin — a hormone that helps glucose (sugar) enter cells so that it can be used as fuel to produce energy — is impaired.

The Phase 2a study included 46 adults with Parkinson’s, ages 30 to 80, who were randomly assigned to either 20 mg bezisterim or a placebo, taken as capsules by mouth twice daily for 28 days, on top of their standard carbidopa/levodopa medication.

Bezisterim resulted in a 2.8-point greater reduction on part 3 of the MDS Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), a measure of how severe motor symptoms are, compared with a placebo. In the MDS-UPDRS, lower scores mean less severe symptoms.

In line with a previous analysis of the data, patients younger than 70, who made up about half of the study population, showed an even greater difference in motor symptoms, an advantage of 4.7 points in favor of bezisterim.

On day 28, nearly one-third (30%) of patients treated with bezisterim reported better motor function in the morning, before taking their standard carbidopa/levodopa medication, whereas none of the patients on a placebo experienced this.

Participants treated with bezisterim also had less trouble falling or staying asleep than those on a placebo, as measured by the sleep/fatigue domain of the Non-Motor Symptom Scale (NMSS). In the NMSS, lower scores mean less severe symptoms.

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Better sleep, calmer legs

Patients on bezisterim showed a 2.4-point reduction in the sleep/fatigue domain of the NMSS, while those on a placebo showed a one-point increase. Changes in motor symptoms correlated with changes in non-motor symptoms: That is, the lower the MDS-UPDRS scores, the lower the NMSS scores.

When asked about restless legs, patients on bezisterim showed a 0.89-point reduction from the start of the study to day 28, indicating less urge to move the legs, whereas patients on a placebo showed a 0.99-point increase over the same time window.

“These findings warrant confirmation in patients who are significantly impacted by these non-motor symptoms,” researchers wrote in the presentation slides. The researchers had previously reported that add-on treatment with bezisterim was safe and well tolerated.

“These findings … demonstrate potential intrinsic and levodopa-enhancing activity of bezisterim that is consistent with data from animal models and support further clinical investigation of bezisterim in late-phase trials,” Palumbo said.

BioVie plans to launch a Phase 2b study of bezisterim as a first-line, stand-alone treatment for newly diagnosed Parkinson’s. Its goal is to test how well bezisterim eases motor symptoms against a placebo when given on its own for up to six months.