Oral androgen receptor agonist improves sarcopenia, encephalopathy in cirrhosis
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Key takeaways:
- LPCN 1148 increased Skeletal Muscle Index at L3 spine level by the equivalent of 7.9%.
- Treatment also resulted in improvement in total decompensation events, hepatic encephalopathy and total hospital days.
BOSTON — LPCN 1148, an oral androgen receptor agonist, improved sarcopenia, hepatic encephalopathy and other biomarkers associated with end-stage liver disease among men with advanced cirrhosis and clinical decompensation.
“Sarcopenia is commonly present in those with decompensated cirrhosis and impacts clinically meaningful outcomes,” Arun J. Sanyal, MBBS, MD, director of the Stravitz-Sanyal Institute for Liver Disease & Metabolic Health and interim chair of the division of gastroenterology, hepatology and nutrition at Virginia Commonwealth University School of Medicine, said at The Liver Meeting. “There are multiple mechanisms that contribute to sarcopenia in cirrhosis. Of these, androgens are known to enhance muscle mass by inhibiting myostatin ... This is, of course, relevant because 90% of males with cirrhosis have low-free testosterone.”
Sanyal continued: “LPCN 1148 is an oral androgen receptor agonist and is a dosage form comprising testosterone dodecanoate, a unique prodrug of the endogenous hormone. ... We hypothesized that LPCN 1148 will improve sarcopenia, sarcopenia-related outcomes and clinically significant outcomes in patients with cirrhosis.”
In a phase 2, proof-of-concept study, 29 men (mean age, 59 years; BMI 29 kg/m2) with sarcopenia and cirrhosis awaiting liver transplantation received either oral LPCN 1148 (n = 15) or placebo (n = 14) for 24 weeks. At baseline, mean MELD was 17 and hemoglobin was 12.2 g/dL; most patients (86%) had experienced at least two unique decompensation events and 79% were on therapy for hepatic encephalopathy (HE).
The primary studied endpoint was change in Skeletal Muscle Index (L3 region, L3-SMI) at 24 weeks compared with baseline. Additional studied outcomes included “feel and function” parameters, survival outcomes and biomarkers.
Results showed L3-SMI increased among those in the treatment group compared with placebo (3.62 cm2/m2 vs. –0.74 cm2/m2) at week 24, equating to a 7.9% increase in L3-SMI with LPCN 1148. Those in the treatment group also experienced fewer total decompensation events (7 vs. 10) and episodes of overt HE higher than grade 1 (2 vs. 6), as well as total days in the hospital (54 vs. 117).
Further, significantly more treated patients reported feeling “very much” or “moderately better” (33.3% vs. 0%), and researchers noted symptom improvement as early as week 4. Anemia resolved among 36% vs. 14% of participants, and other secondary measures, such as the 6-minute walk test (270 ft. vs. –16 ft.) and the EncephalApp Stroop Test, also favored LPCN 1148.
Treatment-emergent adverse events were similar between groups with no incident cases of hepatocellular carcinoma, drug-induced liver injury or thrombosis.
“LPCN 1148... improved sarcopenia in adult male patients with cirrhosis,” Sanyal concluded. “We believe these data demonstrate that this molecule is well-tolerated and improves multiple clinically significant and surrogate outcomes in [male] patients with advanced cirrhosis and supports its further development in this population while patients await transplant or as a palliative measure.”