Subjects: TRI, FDA
NEURELIS ANNOUNCES FIRST HEALTHY SUBJECTS DOSED IN INVESTIGATIONAL STUDY OF NRL-1049, A RHO KINASE (ROCK) INHIBITOR WITH POTENTIAL TO TREAT CEREBRAL CAVERNOUS MALFORMATIONS
- First in human study will evaluate safety, tolerability, and pharmacokinetic parameters of NRL-1049, a Rho kinase (ROCK) inhibitor
SAN DIEGO, Calif., March 24, 2023 /PRNewswire/ -- Neurelis, Inc., announced the first two cohorts dosed in the investigational clinical trial of NRL-1049, a Rho kinase (ROCK) inhibitor, a potential treatment for people living with cerebral cavernous malformations (CCM), a disease characterized by abnormally enlarged capillary cavities in the brain and spinal cord. This is a first-in-human study designed to establish safety, tolerability, and pharmacokinetic parameters of NRL-1049.
"We are excited to initiate this study because it will build upon the preclinical activity and tolerability observed in preclinical studies. People afflicted with CCMs have limited treatment options, which include management of seizures through anti-seizure medications and in limited selected cases surgical intervention to remove lesions," said Founder and CEO of Neurelis, Craig Chambliss. "If successful, NRL-1049 has the potential to be the first FDA approved treatment for CCMs."
An analysis of NRL-1049 preclinical data showed that transgenic mice showing the mutations for familial CCMs treated with NRL-1049 showed a significant dose-dependent reduction in lesion volume and a reduction in hemorrhage (iron deposition) near lesions at all doses after treatment compared with placebo.
NRL-1049 will be evaluated in a randomized, dose-escalation, double-blind, placebo-controlled single ascending dose study to establish safety, tolerability, and pharmacokinetic parameters in healthy volunteers. The primary objectives of the study are to determine the maximum tolerated dose (MTD) of a single oral dose of NRL-1049 and collect data on clinical safety and tolerability.
"The NRL-1049 Phase 1 study was built on strong preclinical data, both providing greater insight into its potential, which helped inform our decision to initiate this clinical program," said Chief Scientific Officer, Stuart Madden, PHD, CCHEM, FRSC. "We are excited about what NRL-1049 could mean for patients and appreciate the contributions of the trial volunteers and investigators."
About NRL-1049
In June 2021, Neurelis licensed NRL-1049 from BioAxone BioSciences, Inc., which is an investigational pre-clinical stage small molecule, Rho kinase (ROCK) inhibitor designed to potentially reduce the accumulation of new lesions, as well as alleviate neurological symptoms associated with CCMs. Earlier this year, the investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) was accepted for NRL-1049.
Cerebral Cavernous Malformations
CCMs are a disease characterized by abnormally enlarged capillary cavities, most commonly found in the cerebral cortex, brainstem, and spinal cord. CCMs can present as a single lesion or as multiple lesions. Depending on lesion size and location, CCMs can be "clinically silent" or can present with clinical symptoms ranging from headaches to focal neurological deficits, seizures, and cerebral hemorrhage. People afflicted with CCMs have limited treatment options, which include management of seizures through anti-seizure medications and surgical intervention to remove lesions (e.g., microsurgical resection, stereotactic radiosurgery). There are no FDA-approved therapeutic treatments for CCMs. Most cavernous malformations are conservatively managed by observing for changes in appearance, recent hemorrhages, or other clinical symptoms.
About Neurelis
Neurelis, Inc., is a commercial-stage neuroscience company focused on the development and commercialization of therapeutics for the treatment of epilepsy and orphan neurologic disorders characterized by high unmet medical need. In 2020, the FDA approved Neurelis' VALTOCO® (diazepam nasal spray) as an acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from an individual's usual seizure pattern in adult and pediatric patients 6 years of age and older. VALTOCO is a proprietary formulation of diazepam incorporating the science of INTRAVAIL®. Intravail's transmucosal absorption enhancement technology enables the noninvasive delivery of a broad range of protein, peptide and small-molecule drugs. In its approval of VALTOCO, the U.S. Food and Drug Administration also granted Neurelis Orphan Drug Exclusivity and recognized VALTOCO's intranasal route of administration as a clinically superior contribution to patient care over the previously approved standard-of-care treatment (a rectal gel formulation of diazepam). For more information on VALTOCO, please visit http://www.valtoco.com/. In addition to VALTOCO, Neurelis is developing NRL-4 as a noninvasive rescue therapy to address the escalation of acute agitation symptoms associated with schizophrenia and bipolar 1 mania in adults. In addition, Neurelis is developing NRL-1049 (previously known as BA-1049), an investigational, Phase I stage small molecule Rho kinase (ROCK) inhibitor, for the treatment of cerebral cavernous malformations (CCMS), a rare disorder of the central nervous system (CNS). For more information on Neurelis, please visit http://www.neurelis.com/. For the latest scientific information on VALTOCO, please visit https://www.neurelismedicalaffairs.com/.
Important Safety Information about VALTOCO:
Indication
VALTOCO® (diazepam nasal spray) is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 6 years of age and older.
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS |
? Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. |
? The use of benzodiazepines, including VALTOCO, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing VALTOCO and throughout treatment, assess each patient's risk for abuse, misuse, and addiction. |
? The continued use of benzodiazepines may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Although VALTOCO is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of VALTOCO may precipitate acute withdrawal reactions, which can be life-threatening. For patients using VALTOCO more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue VALTOCO. |
Contraindications: VALTOCO is contraindicated in patients with:
- Hypersensitivity to diazepam
- Acute narrow-angle glaucoma
Central Nervous System (CNS) Depression
Benzodiazepines, including VALTOCO, may produce CNS depression. Caution patients against engaging in hazardous activities requiring mental alertness, such as operating machinery, driving a motor vehicle, or riding a bicycle, until the effects of the drug, such as drowsiness, have subsided, and as their medical condition permits.
The potential for a synergistic CNS-depressant effect when VALTOCO is used with alcohol or other CNS depressants must be considered, and appropriate recommendations made to the patient and/or care partner.
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including VALTOCO, increase the risk of suicidal ideation and behavior. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or unusual changes in mood or behavior.
Glaucoma
Benzodiazepines, including VALTOCO, can increase intraocular pressure in patients with glaucoma. VALTOCO may be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. VALTOCO is contraindicated in patients with narrow-angle glaucoma.
Neonatal Sedation and Withdrawal Syndrome
Use of VALTOCO late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Monitor neonates exposed to VALTOCO during pregnancy or labor for signs of sedation and monitor neonates exposed to VALTOCO during pregnancy for signs of withdrawal; manage these neonates accordingly.
Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative
VALTOCO is not approved for use in neonates or infants. Serious and fatal adverse reactions, including "gasping syndrome," can occur in neonates and low-birth-weight infants treated with benzyl alcohol?preserved drugs, including VALTOCO. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known.
Adverse Reactions
The most common adverse reactions (at least 4%) were somnolence, headache, and nasal discomfort.
Diazepam, the active ingredient in VALTOCO, is a Schedule IV controlled substance.
To report SUSPECTED ADVERSE REACTIONS, contact Neurelis, Inc. at 1-866-696-3873 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).
Please read full Prescribing Information, including Boxed Warning.
Contacts:
Neurelis:
Brittany Bradrick, Chief Operating Officer and Chief Financial Officer, +1 858 251 2135
Media:
Glenn Silver, FINN Partners, +1 646 871 8485
SOURCE Neurelis, Inc.
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