Nayzilam (USL261) is a rescue medication designed as a nasal spray for prolonged seizures such as those that occur in Batten disease. Nayzilam was first developed by Proximagen, but the rights to the medication were later acquired by UCB.

About rescue medications

Batten disease is a serious genetic disorder, which causes loss of vision, progressive degradation of mental and physical abilities, and seizures. Prolonged seizures are very dangerous and can be life-threatening.

Rescue medications are medicines that can be given to stop a prolonged seizure or a cluster of seizures. The advantage of Nayzilam is that it can be administered through the nose without the patient having to breathe deeply, which most patients are incapable of doing during a seizure.

How Nayzilam works

Nayzilam is a preparation of midazolam, a type of benzodiazepine.

In normal nerve signaling, a message is sent from one brain cell to another by changing the flow of charged particles in and out of the cells. When this signaling is overactive and does not end after a message has been sent, a seizure occurs.

Benzodiazepines enhance the effect of an inhibitory signaling molecule called gamma-aminobutyric acid (GABA). GABA reduces the excitability of nerve cells. Benzodiazepines bind to a specific protein found on the surface of nerve cells to which GABA also binds, increasing the effect of GABA in the brain and reducing the severity and incidence of seizures.

Nayzilam in clinical trials

A clinical trial compared the pharmacokinetics (movement in the body) of Nayzilam nasal spray, midazolam administered as an intravenous infusion, and midazolam injected through the nose in 25 healthy adult volunteers. The results, published in the scientific journal Neurology, showed that Nayzilam had a better bioavailability than injected midazolam — meaning that more of the treatment reached the blood from the nasal spray.

A Phase 1 trial was conducted to determine the pharmacokinetics of Nayzilam in adults, ages 65 and older. A total of 18 healthy volunteers, 65 and older, and 12 healthy volunteers, ages 18 to 40, were treated with either 2.5 or 5 mg of Nayzilam. The results were published in the journal Epilepsy Behavior and showed no significant differences in how the treatment was absorbed or how long it lasted in the body regardless of age.

A Phase 3 trial (NCT01999777) examined the safety and effectiveness of Nayzilam in treating intermittent bouts of increased seizure activity in patients admitted to epilepsy monitoring units at hospitals around the world. A total of 62 patients, ages 12 and older, were randomly assigned to receive either Nayzilam or placebo. The primary outcome was whether the medication ended seizures within 10 minutes of treatment. The secondary outcome was whether any seizures reoccurred within six hours of treatment. The results of this trial have not been published yet.

Another Phase 3 trial (NCT01390220) examined the safety and effectiveness of Nayzilam in treating seizure clusters. A total of 201 patients, ages 12 and older, with seizure clusters were randomly assigned to receive either Nayzilam or a placebo. The primary outcomes of the trial were the termination of seizures within 10 minutes after Nayzilam administration, and no recurrence of seizures between 10 minutes and six hours after administration.

The results of the trial were presented at the 2017 Antiepileptic Drug & Device Trials Meeting and showed that Nayzilam was a significant improvement over placebo in terms of both successfully ending the seizure and decreasing the recurrence of seizures while Nayzilam was still in the bloodstream.

Other information

Nayzilam has been granted orphan drug status and fast track designation from the U.S. Food and Drug Administration. A new drug application for Nayzilam has been accepted by the FDA, meaning it could be approved in the U.S. as soon as 2019.

The side effects of Nayzilam are expected to be identical to those for midazolam, including headaches, low blood pressure, sleepiness, and respiratory depression.

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