2214-PUB: An Open-Label Study of Gemcabene in Adults with Familial Partial Lipodystrophy
Authors: AKINCI BARIS , SWAIDAN MARIO , FOSS-FREITAS MARIA CRISTINA , LUO YINGYING , NEIDERT ADAM H. , HENCH RITA P. , CHENEVERT THOMAS L. , LONGCORE AMY , BAKKER-ARKEMA REBECCA , BISGAIER CHARLES L. , ORAL ELIF A. 
Published: June 2020

Familial Partial Lipodystrophy (FPLD) is characterized by partial loss of subcutaneous fat accompanied by metabolic abnormalities, not responding well to conventionally available therapies. Gemcabene calcium is a monocalcium salt of a dialkyl ether dicarboxylic acid having 2 terminal gem dimethyl carboxylate moieties. Previous studies have shown that gemcabene has the potential to enhance the clearance of VLDL cholesterol and block the overall production of hepatic triglyceride and cholesterol synthesis.
The objective of this study was to assess the overall efficacy and safety of gemcabene in a small number of patients with FPLD who have a fasting triglyceride value ≥ 250 mg/dL and hepatic steatosis ≥10%. Five female patients with FPLD (age range: 39-63; 2 with LMNA R482Q and 3 with no causative genetic variant) were included. Patients received a 300 mg/day dose of gemcabene for the first 12 weeks, with randomization to either 300 mg/day (n=3) or 600 mg/day (n=2) for another 12 weeks. Four patients completed treatment and a fifth one discontinued at 22 weeks (data carried forward). Gemcabene treatment resulted in a median change in serum triglycerides of -19.6% at week 12 (the primary endpoint). The range of triglyceride responses was +40.4% to -52.9%, with 3 patients showing decreases. Liver fat fraction showed a reduction in 2 of the 3 responding patients, although an increase in hepatic fat was observed in 2 patients with LMNA R482Q at the end of the study. Four of 5 patients showed slight reductions in HbA1c at week 12 and one patient had no change. Best responding patients fit the previous profiles of gemcabene responders from previous studies (elevated baseline LDL along with triglycerides). This limited proof-of-concept study provided evidence that gemcabene has the potential to lower triglycerides in certain FPLD patients at 12 weeks. Heterogeneous patient responses observed in this study might be related to different genetic etiologies; however further studies are needed to understand this phenomenon.

Disclosure
B. Akinci: Advisory Panel; Self; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals. Research Support; Self; Gemphire Therapeutics Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Servier. M. Swaidan: None. M. Foss-Freitas: None. Y. Luo: None. A.H. Neidert: None. R.P. Hench: None. T.L. Chenevert: None. A. Longcore: Consultant; Self; Gemphire Therapeutics Inc., Viacyte, Inc. R. Bakker-Arkema: None. C.L. Bisgaier: Advisory Panel; Self; Imagine Pharma. Board Member; Self; Gemphire Therapeutics Inc., Hygieia. Employee; Self; Gemphire Therapeutics Inc. Stock/Shareholder; Self; Gemphire Therapeutics Inc., Hygieia, Imagine Pharma. E.A. Oral: Consultant; Self; Aegerion Pharmaceuticals, Akcea Therapeutics, Regeneron Pharmaceuticals. Research Support; Self; Aegerion Pharmaceuticals, Akcea Therapeutics, Gemphire Therapeutics Inc., GI Dynamics Inc., Regeneron Pharmaceuticals.

Funding
Gemphire Therapeutics Inc.