Lipocine Announces LPCN 1154 Meets Bioequivalence with IV Brexanolone in Pivotal Study
Lipocine has announced that its oral drug LPCN 1154 met bioequivalence criteria in a pivotal study comparing it to IV brexanolone for treating postpartum depression (PPD). The study met key pharmacokinetic (PK) parameters: Cmax, AUC0-t, and AUC0-∞. LPCN 1154 also showed no sedation or somnolence events and was well tolerated. The company aims to submit a New Drug Application (NDA) by the end of Q4 2024. PPD affects around 500,000 women in the U.S. annually, with a significant unmet need for effective, fast-acting oral treatments.
- LPCN 1154 met bioequivalence criteria in pivotal PK study.
- No sedation or somnolence events observed with LPCN 1154.
- Targeting NDA submission by end of Q4 2024.
- PPD market size and awareness are increasing.
- LPCN 1154 showed higher Ctrough than IV brexanolone.
- Study results exclude one participant due to outlier criteria.
- Reported adverse events include headache, fatigue, and dizziness.
Insights
Bioequivalence studies are a cornerstone in the development of generic drugs or new formulations of existing drugs. In this case, Lipocine’s LPCN 1154 achieving bioequivalence to IV brexanolone is significant for postpartum depression (PPD) treatment. Here’s why: Intravenous brexanolone is already an approved treatment for PPD, but its administration requires a hospital setting and supervision, which is a hurdle for many patients.
By matching the pharmacokinetics of the IV formulation, LPCN 1154 (oral form) has demonstrated it can achieve similar therapeutic levels in the bloodstream as the IV version. This suggests that patients can receive the same benefits without the need for invasive procedures. The absence of sedation or somnolence events is another excellent sign, indicating that the new oral formulation could potentially offer a better safety profile with more convenience.
However, it’s important to note that bioequivalence does not guarantee clinical efficacy and safety in the wider population. Further clinical trials and longer-term studies will be needed to confirm these findings. Still, the preliminary data is promising and aligns with the industry's move towards more patient-friendly drug delivery methods.
The market potential for LPCN 1154 is substantial given the unmet need in treating PPD. Currently, the PPD market is underserved, with few effective treatments available. The fact that approximately 500,000 women in the U.S. are affected by PPD annually and up to 175,000 suffer from moderate to severe forms, underscores the market size and demand for new treatments.
Lipocine’s oral formulation, which promises a more convenient and potentially safer option, could capture a significant share if it receives FDA approval. Additionally, the increased awareness and diagnosis of PPD will likely drive market growth. Thus, the oral brexanolone could not only meet a critical need but also serve as a lucrative opportunity for Lipocine.
Moreover, if the company can file the NDA by the end of Q4 2024 as planned, it stands to benefit from being among the first to market with an oral alternative to IV brexanolone. This could enhance its competitive positioning and drive long-term growth.
- Met standard bioequivalence (BE) criteria Cmax, AUC0-t, and AUC0-∞
- Ctrough criterion was met
- LPCN 1154 was well tolerated with no sedation or somnolence events observed
- On track for NDA filing, targeted by end of Q4 2024
"I'm pleased with the positive outcome of this pivotal study which brings us a step closer to potentially offering a differentiated preferred treatment option for PPD patients in need," said Dr. Mahesh Patel, President and CEO of Lipocine. "PPD is a serious and potentially life-threatening condition. LPCN 1154 is targeted to be a highly effective, oral, fast-acting and short duration treatment option. We believe a 48-hour oral dosing duration with fast onset of efficacy would be an important solution for patients and caregivers."
Per published FDA bioequivalence guidance1, the criteria to establish bioequivalence are that Geometric Mean Ratios (GMR) and corresponding
The pivotal PK study was an open label, randomized, crossover study in 24 healthy postmenopausal women utilizing the "to be marketed" formulation and oral dosing regimen of LPCN 1154 and the commercial IV brexanolone formulation using the approved high dose infusion regimen (IV90). The primary objective of the study is to compare the PK of a multi-dose regimen of oral LPCN 1154 (test product) to IV infusion brexanolone (reference product).
Twenty-four post-menopausal women were randomized (safety set), and all completed dosing in both study periods. The PK analysis data set includes 23 participants; data from one participant meeting outlier criteria was excluded.
PK Comparisons of LPCN 1154 vs. IV90 Brexanolone
LPCN 1154 and IV90 brexanolone were bioequivalent based on GMRs and
PK Parameter | GMR (%) Test vs. Reference | Test vs. Reference | Test vs. Reference |
Cmax | 105 | 92 | 120 |
AUC0-∞ | 97 | 88 | 107 |
AUC0-t | 88 | 80 | 99 |
n=23; Outlier participant presented PK results for the IV administration period greater than 70 standard deviations away from the PK data set mean for all PK parameters included above; LB = lower bound, UB = upper bound, t = 100 hours for AUC0-t |
LPCN 1154 treatment was well tolerated with no sedation nor somnolence events observed. All events were mild to moderate, and no severe or serious adverse events occurred. Reported study related events were venipuncture site reaction, headache, arthralgia, fatigue, dizziness, low back pain, and pelvic pain and no event was reported by more than two participants.
PPD 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. There is an unmet need for an oral fast-acting product with an improved efficacy and safety profile to treat PPD. Oral LPCN 1154 comprising a bioidentical neuroactive steroid is designed to provide rapid relief with robust efficacy and 48-hour outpatient dosing.
Recent reports suggest that the market size for PPD is larger than previously estimated. Approximately 500,000 women are affected by PPD annually in
About LPCN 1154
LPCN 1154 is an oral formulation of brexanolone in development targeted for administration resulting in rapid relief of PPD. Brexanolone is a bioidentical to naturally occurring neuroactive steroid, allopregnanolone, a positive allosteric modulator of y-aminobutyric acid (GABA) receptor. LPCN 1154 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.
About Postpartum Depression and Unmet Needs
PPD is a major depressive disorder with onset either during pregnancy or within four weeks of delivery, with symptoms persisting up to 12 months after childbirth. Hormonal changes leading to GABA dysfunction are common in depression and pregnancy. Symptoms of PPD include hallmarks of major depression, including, but not limited to, 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. Results from a recent survey (Truist Securities Research, January 2024) show that obstetricians believe approximately 20
About Lipocine
Lipocine is a biopharmaceutical company leveraging its proprietary technology platform to augment therapeutics through effective oral delivery to develop differentiated products. Lipocine has drug candidates in development as well as drug candidates for which we are exploring partnering. Our drug candidates represent enablement of differentiated, patient friendly oral delivery options for favorable benefit to risk profile which target large addressable markets with significant unmet medical needs.
Lipocine's clinical development candidates include: LPCN 1154, oral brexanolone, for the potential treatment of postpartum depression, LPCN 2101 for the potential treatment of epilepsy, LPCN 2203 an oral candidate targeted for the management of essential tremor, LPCN 2401 an oral proprietary combination of anabolic androgen receptor agonist and α-tocopherol, an antioxidant, as an adjunct therapy to incretin mimetics, as an aid for improved body composition in chronic weight management and LPCN 1148, a novel androgen receptor agonist prodrug for oral administration targeted for the management of symptoms associated with liver cirrhosis. Lipocine is exploring partnering opportunities for LPCN 1107, our candidate for prevention of preterm birth, LPCN 1154, for rapid relief of postpartum depression, LPCN 1148, for the management of decompensated cirrhosis, and LPCN 1144, our candidate for treatment of non-cirrhotic NASH. TLANDO, a novel oral prodrug of testosterone containing testosterone undecanoate developed by Lipocine, is approved by the FDA for conditions associated with a deficiency of endogenous testosterone, also known as hypogonadism, in adult males. For more information, please visit www.lipocine.com.
Forward-Looking Statements
This release contains "forward-looking statements" that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and include statements that are not historical facts regarding our product development efforts, the application of our proprietary platform in developing new treatments, our product candidates and related clinical trials, the timing and outcome of product studies, our development of and filing of a NDA with the FDA for LPCN 1154, and the potential uses and benefits of our product candidates. Investors are cautioned that all such forward-looking statements involve risks and uncertainties, including, without limitation, the risks that we may not be successful in developing product candidates, we may not have sufficient capital to complete the development processes for our product candidates, we may not be able to enter into partnerships or other strategic relationships to monetize our non-core assets, the FDA will not approve any of our products, risks related to our products, expected product benefits not being realized, clinical and regulatory expectations and plans not being realized, new regulatory developments and requirements, risks related to the FDA approval process including the risk that we do not ultimately receive FDA approval for LPCN 1154, the results and timing of clinical trials, patient acceptance of Lipocine's products, risks related to the manufacturing and commercialization of Lipocine's products, and other risks detailed in Lipocine's filings with the SEC, including, without limitation, its Form 10-K and other reports on Forms 8-K and 10-Q, all of which can be obtained on the SEC website at www.sec.gov. Lipocine assumes no obligation to update or revise publicly any forward-looking statements contained in this release, except as required by law.
1FDA Guidance, Statistical Approaches to Establishing Bioequivalence December 2022
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