Women With Epilepsy – LPCN 2101
Product Candidate: LPCN 2101
30% of patients with epileptic seizures have drug-resistant epilepsy.
Product Attributes:
LPCN 2101 is an oral formulation of a new chemical entity (NCE), a neuroactive steroid for epilepsy. NAS of LPCN 2101 is chemically similar to a naturally occurring neuroactive steroid, a positive allosteric modulator of Ɣ-aminobutyric acid (GABA) receptor, representing a novel mechanism of action specifically targeted for patients with refractory epilepsy experiencing uncontrolled seizures.
LPCN 2101 is being developed as an antiepileptic (AED) for women with epilepsy (“WWE”) and Acute seizure management through the prevention of seizure recurrence and reducing seizure cluster occurrence. NASs have been shown to have anti-seizure properties in pre-clinical and clinical studies. LPCN 2101, being bioidentical to endogenous NAS, may provide a superior benefit-to-risk ratio over currently approved AEDs.
While targeting the goal of seizure control, LPCN 2101 also has the potential for additional benefits in psychiatric disorders comorbidities (e.g., anxiety and/or depression) and sleep impairment. Moreover, these oral endogenous NASs could potentially address some of the fetal toxicity concerns related to unplanned or planned pregnancy in women.
Lipocine has completed pre-clinical and Phase 1 studies for LPCN 2101, which demonstrated chronic administration safety and tolerability, and promising PK results demonstrating first oral enablement of the NAS through achievement of the therapeutically relevant levels with our proprietary technology. Our LPCN 2101 IND was accepted by the FDA for adults with epilepsy.
About Indication:
Epilepsy is a symptom of a neurological problem that causes sudden, brief seizures. It can occur as a result of a neurological injury, a structural brain lesion, as a part of many systemic medical diseases or may be genetic in origin. Epilepsy is a disorder of the brain that causes seizures, affecting the physical, mental, and social well-being of persons, and is associated with a 2 to 3 times greater mortality rate compared with the general population.
About 60-65% of epilepsy is idiopathic and about 30% of patients are refractory (i.e., epilepsy not well managed with currently available Anti-Seizure Medications (“ASMs”). Epilepsy is the most common neurological disorder during pregnancy.
Comorbidities such as depression and anxiety may be co-treated with therapies that do not aggravate seizures and have no drug interaction with the ASM used for epilepsy. Epileptic patients are 5-20 times more likely to develop depression.
While the lowest effective dose and monotherapy are preferred, management of patients with epilepsy is focused on controlling seizures, avoiding adverse events, and maintaining quality of life.
Women with epilepsy:
It is estimated that approximately 900,000 childbearing (“CB”) aged women suffer from active epilepsy in the U.S. Women of CB age with epilepsy face many additional challenges due to hormonal influences on seizure activity and endocrine function throughout the different phases of their reproductive cycles. Elevated estrogen or decreased progesterone levels can exacerbate seizure frequency. Often, these women experience hormonal and endogenous NAS imbalances, coupled with fluctuations in the blood levels of ASMs that impact control of seizures, efficacy of oral contraceptives, any coexisting anxiety and/or depression and any associated sleep impairment.
Unmet needs for women with epilepsy
Women with epilepsy face specific challenges throughout their lifespan because of seizures, ASMs, and hormonal fluctuations. While numerous molecules have been approved for the treatment of epilepsy in the U.S., no epilepsy drug has been specifically approved for women.
Women with epilepsy were once counseled to avoid pregnancy, but epilepsy is no longer considered a contraindication to pregnancy. Caregivers for WWE in the preconception phase either intending to start a family (planning pregnancy) or using contraception to prevent an unplanned pregnancy face significant challenges to balance seizure control efficacy with the selection and dosage of ASMs and ASM-related risks such as, among other risks, fetal-neonatal toxicity, contraception failure, and psychiatric side effects.
Moreover, risks associated with ASMs are considerable early in pregnancy; therefore, it is necessary that WWE of CB age undergo counseling, monitoring, and adjustment to the most appropriate ASM prior to becoming pregnant. It is preferable that WWE of CB age discuss seizure control with their doctor for at least 6 months before conception and, if possible, cease ASM therapy or use the lowest effective dose of a single anticonvulsant according to the type of epilepsy and the fetal toxicity of the ASM. Anxiety, depression, lack of adherence to ASM, and/or contraception failure may be experienced by women who are worried about unplanned pregnancy or are late in confirming pregnancy, planned or unplanned. ASMs can reduce the efficacy of oral contraceptives, compounding this problem. There remains an unmet need to make available a treatment option specifically for women with active epilepsy.
Unmet needs for Acute Repetitive Seizures (ARS)
ARS is also known as cluster seizures, serial seizures, crescendo seizures, seizure flurries, recurrent seizures, or cyclical seizures, and is defined as more than 2-3 seizures within a day, often within 6-8 hours despite being treated with ASMs. 30-40 % of patients experiencing ARS have refractory epilepsy with uncontrolled epilepsy approximating one M patients including more than 150,000 also experience seizure clusters. Seizure clusters increase a patient’s risk for status epilepticus, which could result in death and increased emergency room visits.
ARS is mostly managed via rescue medicines in an emergency setting that require fast onset via administration through nasal or rectal route with drawbacks of limited efficacy, need of assistance, and approved for short use duration.
There is a need for new AED that could address the drug-resistant in epilepsy.
There remains a need patient friendly, fast acting ASM with a novel MOA to manage ARS in refractory epilepsy as an adjunct or post rescue for longer term use in patients experiencing uncontrolled seizures and improve quality of life.