Lipocine Announces Positive Week 52 Results from LPCN 1148 Phase 2 Study in Patients with Cirrhosis
- Positive Phase 2 results for LPCN 1148 in cirrhosis management
- Increased Skeletal Muscle Index (SMI) maintained through 52 weeks
- Fewer Hepatic Encephalopathy (HE) events with LPCN 1148 therapy
- Well-tolerated treatment with similar AE rates to placebo
- Potential for LPCN 1148 to be a standard of care for cirrhosis
- None.
Insights
The recent Phase 2 clinical study results for LPCN 1148 present a significant development in the treatment of cirrhosis, particularly in addressing sarcopenia and Overt Hepatic Encephalopathy (OHE). The study indicates that LPCN 1148 not only increases Skeletal Muscle Index (SMI) but also reduces the recurrence of OHE, which are both critical factors in the management of cirrhosis patients.
From a medical research perspective, the sustained increase in SMI over a 52-week period is noteworthy. Sarcopenia, or muscle wasting, is a common and serious complication of cirrhosis that can lead to increased morbidity and mortality. Current management strategies are limited and there are no FDA-approved pharmacotherapies targeting this condition. Therefore, the introduction of LPCN 1148 could potentially fill a substantial gap in patient care.
The reduction in OHE events is equally important. Hepatic encephalopathy is a severe neuropsychiatric complication of liver disease and its management is important for improving patient outcomes and quality of life. The longer time to first recurrent OHE event suggests that LPCN 1148 may offer a protective effect against this debilitating condition.
These findings could have a profound impact on the standard of care for cirrhosis patients, potentially leading to better clinical outcomes and reduced hospitalization rates. However, it is essential to consider the safety profile of LPCN 1148, which appears to be well-tolerated with adverse event rates and severities similar to placebo. This is encouraging, but long-term safety data and further large-scale studies will be important to fully understand the benefits and risks of this treatment.
The positive outcomes from Lipocine Inc.'s Phase 2 study of LPCN 1148 have significant pharmacoeconomic implications. The potential reduction in hospitalization days and the decrease in serious adverse events translate into direct cost savings for the healthcare system. Cirrhosis is a chronic condition that imposes a substantial economic burden due to frequent hospitalizations and long-term care needs.
By improving muscle mass and reducing the incidence of OHE, LPCN 1148 could decrease the economic strain on healthcare resources. Fewer hospitalizations and a longer time to OHE recurrence could result in lower healthcare utilization and costs associated with acute care services. Moreover, the improvement in patients' quality of life could lead to indirect cost savings through increased productivity and reduced caregiver burden.
The 'First in Class' designation of LPCN 1148, if approved, suggests that it has a unique mechanism of action that is not found in existing therapies. This novelty could command a premium price in the market, but it would be essential to balance the cost of the drug with the potential savings in healthcare expenditures. Payers and healthcare providers would need to assess the cost-effectiveness of this treatment option carefully.
Furthermore, the pharmacoeconomic rationale presented by Lipocine Inc. could be a persuasive argument for insurance coverage and reimbursement, which is a critical factor for patient access to new therapies. If LPCN 1148 proves to be cost-effective, it could be widely adopted as a standard of care, which would have a substantial impact on the company's market share and revenue.
The announcement by Lipocine Inc. regarding the successful Phase 2 study of LPCN 1148 has the potential to be a significant catalyst for the company's stock. Positive clinical trial results often lead to increased investor confidence and can drive stock prices up, especially when the product addresses a substantial unmet medical need, such as sarcopenia in cirrhosis.
Investors will be closely monitoring the company's upcoming meeting with the FDA to discuss the development path to NDA filing. A clear and favorable regulatory pathway could further boost investor sentiment. Additionally, the market opportunity for a 'First in Class' therapy in advanced cirrhosis management is considerable, given the lack of FDA-approved treatments for sarcopenia in this patient population.
However, investors should also consider the risks associated with the drug development process, including the potential for adverse findings in future studies, regulatory hurdles and challenges in commercialization. The biopharmaceutical sector is highly volatile and while the upside potential for Lipocine Inc. is substantial, the inherent risks cannot be overlooked.
It will also be important to assess Lipocine's financial position and its ability to fund further development and potential commercialization of LPCN 1148. The company's capacity to negotiate favorable partnership or licensing deals could also impact its financial outlook and should be considered in any investment analysis.
- Met primary and Hepatic Encephalopathy (HE) endpoints in Phase 2 study
- Increase in Skeletal Muscle Index (SMI) observed at Week 24 was maintained through 52 weeks
- Participants on placebo increased SMI when switched to LPCN 1148
- Fewer Overt Hepatic Encephalopathy (OHE) events and time to first recurrent OHE event was longer while on LPCN 1148 therapy
- LPCN 1148 was well-tolerated, with AE rates and severities similar to placebo.
- Participants on LPCN 1148 were hospitalized for fewer days
"We are encouraged with the positive results from our Phase 2 study. These results demonstrate that LPCN 1148 treatment benefits patients with cirrhosis who are sarcopenic and have experienced other serious decompensation events such as OHE," said Dr. Mahesh Patel, President and CEO of Lipocine Inc. "Cirrhosis management is a significant unmet medical need with a strong pharmaco-economic rationale. We believe LPCN 1148 both ameliorates sarcopenia and decreases the recurrence of OHE. If approved, this treatment is a compelling opportunity with the potential to be the standard of care as a mono or adjunct therapy in managing advanced cirrhosis."
This Phase 2 proof of concept study was a randomized placebo-controlled study in sarcopenic male patients with cirrhosis on the liver transplant waitlist. In Stage 1, 29 patients were randomized 1:1 to receive either LPCN 1148 or matching placebo for 24 weeks. At Week 24, the open-label extension Stage 2 of the study commenced. During Stage 2, 8 participants who were on placebo in Stage 1 converted to LPCN 1148, and 11 participants who started the study on LPCN 1148 continued treatment with LPCN 1148.
The study's primary endpoint was a change in L3-SMI at week 24. L3-SMI estimates whole body skeletal muscle mass. SMI was analyzed at baseline, and Weeks 12, 24, 36, and 52. Key secondary endpoints included rates of hepatic encephalopathy and the safety/tolerability of LPCN 1148.
Results
All LPCN 1148-treated participants completed Week 24 (n=15), and 10 of 14 placebo participants completed Week 24. During the initial 24 weeks, all LPCN 1148-treated participants had at least one evaluable post-baseline CT scan and are therefore part of the modified intent to treat (mITT) analysis; 10 placebo-treated participants had an evaluable post-baseline CT. As prespecified, L3-SMI analysis was performed on the mITT population (n=25), with the last evaluable post-baseline observation carried forward (LOCF). Of those participants on placebo in Stage 1, 6 out of 8 who went on to receive LPCN 1148 starting at Week 24 had evaluable CT scans in Stage 2.
Primary endpoint
Participants who received LPCN 1148 during Stage 1 had a significant (p<0.01) increase in L3-SMI of 4.1 cm2/m2 (
Table 1: Change in L3-SMI at Week 24 and Week 52
Timepoint | LPCN 1148 | Placebo | LPCN 1148 |
N=15 | N=10 | (Placebo converted) | |
N=6 | |||
Baseline | 47.8 (1.8) | 45.8 (2.3) | 50.1 (2.7)# |
Week 24 CFB | 4.1 (0.9) *† | - 0.6 (1.2) | |
Week 52 CFB | 4.1 (1.1) * | - | 8.1 (1.7) * |
Data are least squares mean (standard error), LOCF.
# For Placebo participants converted to LPCN 1148, baseline is considered Week 24 data.
ANCOVA model with treatment and overall baseline L3-SMI as covariates.
* p<0.01 vs baseline.
† p<0.01 LPCN 1148 vs placebo at Week 24.
‡ Change from baseline in SMI at Week 24 was the study's primary endpoint.
Hepatic Encephalopathy
Recurrent OHE is defined as an event of OHE in a participant with a medical history of HE. Most (22/29,
Initial | LPCN 1148 | Placebo | ||
Stage 1
(Through Week 24) N=15 | Stage 2
(Week 24 to EOS) N=11 | Stage 1 (Placebo)
(Through Week 24) N=14 | Stage 2 – LPCN 1148 (Placebo Converted)
(Week 24 to EOS) N=8 | |
History of HE prior to randomization (n) | 11 | 7 | 11 | 6 |
OHE (events) | 2 | 1 | 6 | 1 |
Recurrent OHE (events) | 1 | 1 | 6 | 1 |
Average time to first | 114 | 294 | 35 | 140 |
Safety set; includes all participants who received study drug in a given stage. Overt HE (OHE) is defined as an event of HE with CTCAE severity ≥ grade 2.
Safety
In this 52-week study, LPCN 1148 was well-tolerated with AE rates and severities similar to those observed in Stage 1 with placebo. Participants experienced fewer serious or severe adverse events when switched from placebo to LPCN 1148. Participants on LPCN 1148 were hospitalized for fewer total days with shorter hospital stays.
There were two deaths reported in placebo-treated participants and one in LPCN 1148-treated participants during the study.
The company plans to share additional results pertaining to other secondary endpoints at upcoming scientific conferences.
Dr. Arun J. Sanyal, MD, Director, Stravitz-Sanyal Institute for Liver Disease & Metabolic Health,
Dr. Jennifer Lai, MD, MBA, UCSF Professor of Medicine, transplant hepatologist, and study principal investigator, added, "The rapid and sustained increases in muscle mass seen in this study with LPCN 1148 are very exciting, especially as there are currently no FDA-approved pharmacotherapeutics for sarcopenia in cirrhosis. The observed trends towards improved clinical outcomes including hepatic encephalopathy support what we know about the importance of increasing and maintaining muscle mass in patients with cirrhosis."
About Cirrhosis
Cirrhosis is an end stage liver disease of varying etiologies such as alcoholic liver disease, chronic viral hepatitis, nonalcoholic fatty liver disease and primary cholangitis. Complications of cirrhosis include decompensation events such as hepatic encephalopathy due to systemic ammonia buildup, variceal bleeding, and ascites, which require frequent hospitalizations. In addition, many patients exhibit sarcopenia (low muscle mass).
Over 382,000 patients have been diagnosed with decompensated liver cirrhosis in the US, with few options for managing their disease other than liver transplant. Poor quality of life is common while waiting for a liver transplant. Although there is a limited supply of donor livers, transplant is the only cure for end-stage cirrhosis.
About HE
HE is a frequent complication and one of the most debilitating manifestations of liver disease, severely affecting the lives of patients and their caregivers. For patients with decompensated liver cirrhosis and sarcopenia, clinical outcomes tend to be worse - both sarcopenia and myosteatosis are associated with an increased risk of HE.
OHE is an episodic neurological disorder with a high recurrence rate. Up to
About LPCN 1148
LPCN 1148 comprises testosterone dodecanoate, a unique androgen receptor agonist. It is targeted as a differentiated intervention option with a novel multimodal MOA to elicit potential benefits in management of cirrhosis and associated comorbidities of cirrhosis.
About the Phase 2 study
This multi-center study enrolled and dosed a total of 29 patients across 8 centers in
Baseline characteristics, including age, disease etiology baseline L3-SMI, and other comorbidities were generally well-balanced between groups. Overall, the average baseline Model for End-Stage Liver Disease (MELD) score was 16.8, and
About Lipocine
Lipocine is a biopharmaceutical company leveraging its proprietary technology platform to augment therapeutics through effective oral delivery to develop products for CNS disorders. 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 and LPCN 1148, an oral prodrug of bioidentical testosterone 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 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, our product candidates and related clinical trials, our strategic plans for developing products to treat CNS disorders, our ability to monetize non-core product candidates, including through entering into partnering arrangements, the application of our proprietary platform in developing new treatments for CNS disorders, the timing and completion of regulatory reviews, outcomes of clinical trials of our product candidates, the potential uses and benefits of our product candidates, the potential uses and benefits of LPCN 1148, and the timing of and our ability to make any NDA filing relating to LPCN 1148. 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 to treat CNS disorders, 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 receipt of regulatory approvals and our ability to utilize a streamlined approval pathway for LPCN 1154, the results and timing of clinical trials, patient acceptance of Lipocine's products, 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.
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SOURCE Lipocine Inc.
FAQ
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