Lipocine Inc. has completed dosing of subjects in its pivotal pharmacokinetic study for LPCN 1154, an oral formulation of brexanolone being developed as a treatment for postpartum depression (PPD). The biopharmaceutical company announced that it anticipates topline results late in the second quarter of 2024, with the goal of submitting a New Drug Application (NDA) by the end of the fourth quarter of 2024.
"We are pleased to complete dosing of participants in this NDA enabling study of LPCN 1154," said Dr. Mahesh Patel, President and CEO of Lipocine. "We look forward to reporting topline results from this study late in the second quarter of 2024."
Streamlined Regulatory Pathway
The pivotal study design has been aligned with the FDA on a streamlined pathway to NDA submission. Lipocine has confirmed FDA acceptance of a proposal for a 505(b)(2) NDA filing enabled by a single pivotal pharmacokinetic study comparing exposure of LPCN 1154 with the approved IV infusion of brexanolone.
The pivotal study is an open-label, randomized, crossover study in 24 healthy postmenopausal women utilizing the "to be marketed" formulation of LPCN 1154 and dosing regimen. The primary objective is to compare the pharmacokinetics of a multi-dose regimen of oral LPCN 1154 to IV infusion brexanolone administered per label instructions. During the two treatment visits, each participant receives both the oral and IV brexanolone regimens in a randomized, crossover manner.
Addressing Significant Unmet Need
Postpartum depression is a major depressive disorder with onset either during pregnancy or within four weeks of delivery, with symptoms persisting for up to 12 months after childbirth. Recent reports suggest that the market size for PPD is larger than previously estimated, with approximately 500,000 women affected by PPD annually in the United States. According to the CDC, an estimated 175,000 women suffer from moderate to severe PPD.
Results from a recent survey by Truist Securities Research in January 2024 show that obstetricians believe approximately 20-40% of their patients may suffer from PPD. Increasing awareness of PPD among physicians and patients is expected to result in higher diagnosis rates and greater numbers of patients seeking treatment.
There is an unmet need for an oral fast-acting product with an improved efficacy and safety profile to treat PPD. Traditional antidepressants, not approved for PPD, have slow onset of action, side effects such as sexual dysfunction and weight gain, and do not demonstrate adequate remission post-acute treatment.
Drug Mechanism and Advantages
LPCN 1154 is an oral formulation of brexanolone targeted for administration resulting in rapid relief of postpartum depression. Brexanolone is bioidentical to naturally occurring neuroactive steroid allopregnanolone, a positive allosteric modulator of γ-aminobutyric acid (GABA) receptor. Hormonal changes leading to GABA dysfunction are common in depression and pregnancy.
Oral LPCN 1154, comprising a bioidentical neuroactive steroid with 48-hour outpatient dosing, is being developed to provide rapid relief with robust efficacy. The treatment is expected to have characteristics that could be particularly appealing to patients with severe PPD, acutely elevated suicide risk, and in whom rapid improvement is a priority while presenting no significant risk of adverse reactions to breastfed infants from exposure to brexanolone.
"LPCN 1154 is targeted to be a highly effective, oral, fast-acting and short duration treatment option for PPD, a serious and potentially life-threatening condition," said Dr. Patel. "We believe a 48-hour oral dosing duration will be important for patients and caregivers. If approved, LPCN 1154 has the potential to be a differentiated preferred treatment option for PPD."
Symptoms of PPD include hallmarks of major depression, including sadness, depressed mood, loss of interest, change in appetite, insomnia, sleeping too much, fatigue, difficulty thinking/concentrating, excessive crying, fear of harming the baby/oneself, and/or thoughts of death or suicide.
