PLC’s continued Regulatory support of Intravail® and its technology has assisted in the advancement of ARS-1 and its product development.
Neurelis Announces That Intravail® Licensee, ARS Pharmaceuticals’ Intranasal Epinephrine Product, Demonstrates Bioequivalent Exposure to Epinephrine Injectors
— ARS Pharmaceuticals’ lead product, ARS-1 (epinephrine nasal spray) to treat severe allergic reactions, has previously been granted Fast Track designation by the U.S. Food and Drug Administration (FDA)
— Neurelis’ lead product, VALTOCO® (diazepam nasal spray), approved by the FDA for seizure cluster rescue, also utilizes Intravail® as a key component of its formulation
— New data further highlight the permeation enhancement potency of Intravail® for both small and large molecules
SAN DIEGO, CA — May 4, 2020 — Neurelis, Inc., announced today that the American Academy of Allergy, Asthma & Immunology (AAAAI) presented promising results for ARS Pharmaceuticals’ lead asset, ARS-1, a 1-mg intranasal epinephrine product utilizing the Intravail® technology. The abstracts released by AAAAI show that ARS-1 results in bioequivalent exposure to epinephrine injection given once and twice, as well as results in a more rapid absorption and onset of hemodynamic effects. ARS-1 is being investigated as a treatment for patients with severe allergic reactions (including anaphylaxis) to food, medications and insect bites that could lead to life-threatening anaphylaxis. The AAAAI press release can be found here.
Neurelis President and CEO Craig Chambliss stated, “This endorsement by AAAAI and latest data on the ability of ARS-1 to provide injection-like absorption with a 1-mg dose of epinephrine administered intranasally provide more validation of the crucial role Intravail plays in the development of innovative products targeting areas of high unmet need. We congratulate the ARS team on their tremendous progress, which has the potential to offer people a convenient and needle-free alternative to epinephrine injection.”
Intravail is a proprietary drug delivery technology that enhances drug absorption across mucous membranes through two mechanisms: (1) paracellular transport via the transient opening of tight junctions between cells, and (2) transcellular transport via vesicle carriers. The science of Intravail enables the non-invasive delivery of a broad range of protein, peptide, and non-peptide drugs, including small molecules. Intravail can be utilized via the oral, buccal, dermal, and intranasal routes of administration, providing several advantages:
- Increased bioavailability – addressing suboptimal absorption and resulting bioavailability
- Application to wide range of molecules – small molecules, therapeutic proteins, peptides, non-peptide macromolecules (up to ~30KDa)
- Safety – odorless, tasteless, non-toxic, non-mutagenic and non-irritating
- Solubility in water/oils – compatible with routine liquid formulation and dispensing processes for ease of scale-up and production
VALTOCO® (diazepam nasal spray), Neurelis’ lead product, also leverages Intravail as a key component of its formulation. VALTOCO was granted approval by the FDA on January 10, 2020, for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in adult and pediatric patients 6 years of age and older.
In addition to VALTOCO, Chambliss said the company’s pipeline utilizes Intravail to develop novel formulations of drugs targeting areas of significant unmet medical needs in central nervous system (CNS) diseases. Neurelis has also been fortunate to partner with other companies who have licensed Intravail, furthering the development of important drugs in a variety of diseases, and continues to expand its strategic partnerships to benefit patients, caregivers and healthcare providers.
VALTOCO is a proprietary formulation of diazepam incorporating the science of Intravail®. Intravail transmucosal absorption enhancement technology enables the noninvasive delivery of a broad range of protein, peptide and small-molecule drugs. In a long-term, open-label, repeat-dose clinical trial, the safety of VALTOCO was evaluated and more than 4,000 seizures were treated. The clinical trial included adult and pediatric patients aged 6 and older. VALTOCO was generally safe and well tolerated during clinical studies. The most common adverse reactions for diazepam (at least 4%) were somnolence, headache and nasal discomfort. For more information on VALTOCO, please visit www.valtoco.com.
About ARS Pharmaceuticals, Inc.
ARS Pharmaceuticals is dedicated to empowering at-risk patients and caregivers to better protect themselves from severe allergic reactions that could lead to anaphylaxis. The company is developing ARS-1, an intranasal epinephrine spray with a unique absorption technology that could be easy to use, convenient and more reliable for patients and loved ones at risk of severe allergic reactions to food, medications and insect bites that could lead to life-threatening anaphylaxis. For more information on ARS and the data published in conjunction with the 2020 AAAAI Annual Meeting, please visit www.ars-pharma.com.
Neurelis, Inc. is an innovation-driven neuroscience company providing a highly differentiated approach to target unmet medical needs. Neurelis is focused on the development and commercialization of product candidates for epilepsy and the broader central nervous system (CNS) market. On January 10, 2020, the U.S. Food and Drug Administration (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. In addition to VALTOCO, the company is developing NRL-2 for intermittent use to control acute panic attacks, NRL-3 as a noninvasive acute therapy to stop seizures that have progressed to status epilepticus and NRL-4 as a noninvasive rescue therapy to address the escalation of psychomotor agitation (PMA) symptoms outside of the medical setting. The Neurelis technology platform includes Intravail®, ProTek® and Hydrogel™, three proprietary, noninvasive drug-delivery and stabilization technologies applicable to a wide range of molecules, including therapeutic proteins, peptides, non-peptide macromolecules and small molecules. For more information on Neurelis, please visit www.neurelis.com.
Important Safety Information about VALTOCO:
Please see full Prescribing Information, including Boxed Warning, and Medication Guide.
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.
IMPORTANT SAFETY INFORMATION
RISK FROM CONCOMITANT USE WITH OPIOIDS
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
- Reserve concomitant prescribing of these drugs for use in 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
Contraindications: VALTOCO is contraindicated in patients with:
- Known 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. Advise patients and caregivers to be alert for these behavioral changes and to immediately report them to a healthcare provider.
Benzodiazepines, including VALTOCO, can increase intraocular pressure in patients with glaucoma. VALTOCO may only be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. VALTOCO is contraindicated in patients with narrow-angle glaucoma.
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.
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 see full Prescribing Information, including Boxed Warning, for additional important safety information.