Lipocine Updates Progress on Phase 3 Clinical Trial in Postpartum Depression with LPCN 1154

Lipocine Inc. reported on Tuesday that one-third of participants have been randomly assigned to treatment in the company's pivotal phase 3 trial of LPCN 1154, an oral formulation of brexanolone for the treatment of postpartum depression (PPD). The company said in the announcement that it expects topline results in the second quarter of 2026. An independent Data Safety Monitoring Board (DSMB) will review interim safety data later this year, with a public update anticipated in the fourth quarter of 2025.¹

The randomized, double-blind study (NCT06979544) is evaluating LPCN 1154 against placebo in women aged 15 years and older with severe PPD. Based on FDA guidance, the trial is being conducted entirely in the outpatient setting without the need for in-clinic medical monitoring.²

"We are very encouraged by the steady enrollment momentum in our pivotal Phase 3 trial and are pleased to see the program advance as planned,"Mahesh Patel, CEO of Lipocine, said in a statement. "LPCN 1154 is designed to be differentiated from existing options for PPD, with its 48-hour dosing schedule, and potential for rapid, meaningful clinical benefit. We believe it has the potential to become the standard of care for women suffering from this condition. We intend to use the data from this phase 3 trial to support a 505(b)(2) NDA submission in 2026."¹

LPCN 1154 is designed for rapid onset of antidepressant effects and is intended to avoid significant exposure to breastfed infants. Brexanolone, an analog of allopregnanolone that modulates GABA-A receptors, is already approved in intravenous form for PPD, but requires a 60-hour inpatient infusion under monitoring.³ Lipocine’s oral formulation is being developed as a more accessible option.

PPD is a major depressive disorder that can begin during pregnancy or within four weeks after delivery, with symptoms that may persist up to 12 months. It is estimated that 1 in 7 women are impacted by the symptoms after giving birth.¹ Manifestations include depressed mood, loss of interest, changes in appetite and sleep, fatigue, cognitive difficulties, and in some cases suicidal ideation or fear of harming the infant.¹ In its statement, Lipocine cites findings of a 2024 survey conducted by Truist Securities Research that found obstetricians estimate 20–40% of their patients may experience PPD, and most report comfort with diagnosing the condition.¹ They also report prescribing traditional antidepressants off label despite their limitations which include slow onset of action and side effects such as weight gain. They are also associated with poor rates of remission in post-acute treatment.¹

Current PPD-Specific Treatment Options

Evidence to date shows that intravenous brexanolone (Zulresso) produces rapid and clinically meaningful improvement in depressive symptoms, with response often evident within days, but uptake has been limited by the need for prolonged inpatient infusion and monitoring requirements.⁴ More recently, oral zuranolone (Zurzuave; Sage Therapeutics), another neuroactive steroid targeting GABA-A receptors, was approved in 2023 as the first oral treatment for PPD, offering a 14-day outpatient dosing regimen.⁵

Lipocine intends to use results from the phase 3 program to support a New Drug Application in 2026 under the FDA’s 505(b)(2) pathway.

References

1. Lipocine Provides Progress Update on LPCN 1154 Phase 3 Clinical Trial in Postpartum Depression (PPD). News release. Lipocene. September 30, 2025. Accessed October 1, 2025. https://www.lipocine.com/news-article/lipocine-provides-progress-update-on-lpcn-1154-phase-3-clinical-trial-in-postpartum-depression-ppd/

2. Halsey G. First Patient Receives Lipocene's LPCN 1154 for Postpartum Depression in Phase 3 Clinical Trial. Patient Care. June 27, 2025. https://www.patientcareonline.com/view/first-patient-receives-lipocene-s-lpcn-1154-for-postpartum-depression-in-phase-3-clinical-trial

3. Zulresso. Prescribing information. Lipocine, 2022. Accessed October 1, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/211371s007lbl.pdf

4. Meltzer-Brody S, Colquhoun H, Riesenberg R, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomized, placebo-controlled, phase 3 trials. Lancet. 2018;392(10152):1058-1070. doi:10.1016/S0140-6736(18)31551-4

5. Deligiannidis KM, Meltzer-Brody S, Gunduz-Bruce H, et al. Effect of zuranolone vs placebo in postpartum depression: a randomized clinical trial. Am J Psychiatry. 2021;178(6):506-516. doi:10.1176/appi.ajp.2020.20050509