LPCN: 1148 Shows Muscle Loss Reversal

By John Vandermosten, CFA

NASDAQ:LPCN

READ THE FULL LPCN RESEARCH REPORT

Lipocine Inc. (NASDAQ:LPCN) provided a pleasant surprise to investors with its strong Phase II results from its LPCN 1148 study as presented in a July 27th press release. A slide presentation was concurrently provided which can be accessed here. A The study was intended to measure the efficacy, safety and tolerability of LPCN 1148 in adult men with cirrhosis of the liver and sarcopenia on the liver transplant waitlist. The primary endpoint was the increase in the L3 skeletal muscle index (L3-SMI)¹ relative to placebo at week 24. Secondary endpoints included rates of decompensation events including hepatic encephalopathy and participant-reported change in symptoms using the Patient Global Impression of Change (PGI-C) scale.²

Subjects in the LPCN 1148 arm demonstrated a material and statistically significant improvement in their muscle mass as measured by the L3-SMI. Active arm participants, with a baseline of 47.8 cm²/m² produced a 3.62 cm²/m² improvement in muscle mass whereas the placebo group saw a slight 0.74 cm²/m² decline from their 45.8 cm²/m² baseline measurement.

Results from the L3-SMI metric also showed improvement after 12 weeks of therapy. Subjects in the active arm produced a 2.64 cm²/m² improvement after 12 weeks, which was statistically significant at the 5% level of significance.

Secondary endpoints examined decompensation events,⁵ including hepatic encephalopathy and change in patient reported symptoms. The number of decompensation events were lower in the active arm, both in terms of number and percentage of total. Subjects administered LPCN 1148 had fewer major decompensation events as compared to the placebo group. There were seven major decompensation events in the active arm and ten in the placebo arm. There were also fewer recurrences of hepatic encephalopathy in the active arm with a longer delay to recurrence.

In addition to the objective measures of muscle mass increase and decompensation events, subjective measures were also taken. Individuals enrolled in the trial reported significant improvement in symptoms as measured by the PGI-C scale. At week 24, one third of LPCN 1148 subjects reported that they felt moderately or very much better. Lipocine’s principal investigators noted that significantly more 1148-treated subjects reported feeling better and that the mean PGI-C score was significantly lower for 1148 subjects at week 24.

The study also observed two hematological benefits using biomarkers. Hemoglobin improved relative to baseline for 1148 subjects while remaining essentially flat for those in the placebo group. The trial also observed resolution of anemia in four patients at week 24 in the active arm compared with no net change in the placebo group.

LPCN 1148 Trial Design

Lipocine’s 1148 study design was a Phase II, multicenter, double-blinded, placebo-controlled study that enrolled male subjects with liver cirrhosis and sarcopenia on the liver transplant waitlist. The two-arm, 1:1 randomized study enrolled 29 subjects of which 25 remained in the modified intent to treat (mITT) population.

Results from the Phase II LPCN 1148 trial were quite good in our opinion, with material and statistically significant improvement in the primary endpoint as well as observed improvement in decompensation events including hepatic encephalopathy and patient symptom perception. The strong results support pursuit of either an additional pivotal study or other accelerated development path to approval with the FDA. Lipocine plans to set up a Type C meeting with the FDA in the second half of 2023, present its findings and determine next steps. With no other approved treatment for cirrhosis, if these results persist in a pivotal or confirmatory study, LPCN 1148 could become standard of care for patients on the liver transplant list and potentially reduce the risk of and the need for liver transplant.

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1. The L3 skeletal muscle index (L3-SMI) is a measurement used to estimate skeletal muscle mass and diagnose sarcopenia (age-related loss of muscle mass and strength). It is calculated using a CT scan is done at the L3 vertebral level to measure the cross-sectional area of skeletal muscle. The cross-sectional muscle area is normalized for stature by dividing it by height in meters squared. The resulting value is the L3 skeletal muscle index (L3-SMI) measured in cm²/m². Normal L3-SMI values are above 55 cm²/m² for men and above 39 cm²/m² for women. Sarcopenia is diagnosed if the L3-SMI is below 55 cm2/m2 for men and below 39 cm²/m² for women. The L3-SMI allows quantification of muscle mass and identification of sarcopenia, which can guide treatment to prevent muscle loss and related adverse health outcomes.

2. The PGI-C scale is a patient-reported outcome measure used to assess symptoms in patients with chronic conditions. The scale allows patients to rate how their symptoms have changed compared to a recall period, usually the past week. Patients select one of the seven following options with responses scored from 1 to in the following order: 1) Substantially improved, 2) Moderately improved, 3) Slightly improved, 4) No change, 5) Slightly worse, 6) Moderately worse, 7) Substantially worse.

3. Source: June 27, 2023 Corporate Presentation: LPCN 1148 Phase 2 Study Week 24 Topline Results

4. Source: June 27, 2023 Corporate Presentation: LPCN 1148 Phase 2 Study Week 24 Topline Results

5. Decompensation events in the context of cirrhosis refer to acute episodes where the liver's function suddenly worsens. This is usually due to complications from the underlying cirrhosis. Some key decompensation events include ascites, hepatic encephalopathy, variceal hemorrhage, spontaneous bacterial peritonitis, hepatorenal syndrome, hepatopulmonary syndrome. Decompensation events often require hospitalization for management. They indicate worsening liver dysfunction and that the cirrhosis is progressing. Goals of treatment are to stabilize the acute event and prevent further decompensation. The number of decompensation events and their severity are strong predictors of morbidity and mortality in cirrhosis. Preventing decompensation is a major goal of therapy for patients with stable compensated cirrhosis.

6. Source: June 27, 2023 Corporate Presentation: LPCN 1148 Phase 2 Study Week 24 Topline Results

7. Source: June 27, 2023 Corporate Presentation: LPCN 1148 Phase 2 Study Week 24 Topline Results

8. Source: June 27, 2023 Corporate Presentation: LPCN 1148 Phase 2 Study Week 24 Topline Results

9. Source: June 27, 2023 Corporate Presentation: LPCN 1148 Phase 2 Study Week 24 Topline Results