FDA approves Ingrezza Sprinkle to treat chorea in Huntington’s
New granulated formulation designed to be sprinkled onto soft foods
The U.S. Food and Drug Administration (FDA) has approved Neurocrine Biosciences’ oral granules formulation of Ingrezza (valbenazine) — called Ingrezza Sprinkle — for treating chorea, or involuntary movements, in adults with Huntington’s disease.
The new formulation, taken once per day, is designed to provide an easier administration option for patients experiencing swallowing issues due to chorea. A previous survey showed that 62% of 78 Huntington’s patients with chorea and their caregivers reported such difficulties, according to a press release from Neurocrine announcing the therapy’s approval.
The original formulation of Ingrezza — oral capsules available at 40, 60, and 80 mg, taken once daily with or without food — was approved by the FDA last year for the same indication. The Ingrezza Sprinkle capsules, available at the same three dosages, are intended to be opened for sprinkling onto soft food. Both formulations offer simple dosing that involves always just one capsule per day.
“We developed Ingrezza Sprinkle to make administration easier for patients who have difficulty swallowing or prefer not to take a capsule,” said Eiry W. Roberts, MD, Neurocrine’s chief medical officer.
“We are pleased to offer the proven efficacy of INGREZZA in reducing uncontrollable movements in a new formulation,” Roberts added.
Like Ingrezza, the new granulated formulation is also cleared for treating adults with tardive dyskinesia, a condition marked by persistent, uncontrollable movements in the face, tongue, and other body parts.
Ingrezza Sprinkle approval comes within 1 year of original formulation’s
Chorea, a hallmark Huntington’s symptom, causes unpredictable movements that affect finger and hand coordination, walking, and swallowing. Over time, it may worsen and make daily activities more difficult. It’s believed the symptom is caused by overactive signaling by dopamine, a major brain signaling molecule involved in motor control.
Ingrezza and Ingrezza Sprinkle contain the same active ingredient, valbenazine, which works by blocking a protein called VMAT2. This protein is involved in the transport and recycling of dopamine at the sites where nerve cells release molecules to communicate with each other.
By reducing the amount of dopamine release by nerve cells, Ingrezza and Ingrezza Sprinkle are expected to ease chorea.
Ingrezza’s approval in the U.S. was based mainly on results from the Phase 3 KINECT-HD clinical trial (NCT04102579). In the study, 128 adults with Huntington’s and chorea were given either Ingrezza or a placebo once a day for 12 weeks, or about three months.
Treatment with Ingrezza over the 12 weeks led to an average reduction of 3.2 points versus the placebo on the total maximal chorea (TMC) part of the 28-point Unified Huntington’s Disease Rating Scale. On that scale, a lower score indicates less severe chorea.
Most of the individuals in KINECT-HD, along with other adults with Huntington’s, were enrolled in an open-label extension study, called KINECT-HD2 (NCT04400331), in which both researchers and participants know the medication being given patients. That ongoing three-year study is assessing Ingrezza’s long-term safety and efficacy.
Interim data from KINECT-HD2 showed that Ingrezza continued to ease chorea after about one year into treatment, with an average reduction of 5.8 points on the TMC score relative to the study’s start. A similar reduction was observed in a small group of participants who were taking antipsychotics.
Data submitted to FDA showed the 2 formulations were bioequivalent
The filing for approval of Ingrezza Sprinkle included details about its chemical composition and how it is manufactured. It also included data showing that Ingrezza and Ingrezza Sprinkle capsules are bioequivalent, meaning that they have comparable safety and and pharmacological properties.
A previous Neurocrine-sponsored study showed that valbenazine is released at sufficient levels when Ingrezza capsules are opened for crushing and sprinkling onto a range of soft foods, or dissolved in water to be given via a feeding tube.
Neurocrine noted in the release that the FDA’s approval “was based on chemistry, manufacturing, and controls information and data demonstrating the bioequivalence and tolerability of Ingrezza Sprinkle compared to Ingrezza capsules.”
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