FRI059 Long-term Follow-up On Partial Lipodystrophy Treated With Leptin Receptor Agonist Mibavademab(REGN4461)

Abstract

Abstract Disclosure: M.C. Foss de Freitas: Advisory Board Member; Self; PTC Therapeutics. A. DillGomes: None. A. Neidert: None. S. Podgrabinska: Employee; Self; Regeneron Pharmaceuticals. B. Olenchock: Employee; Self; Regeneron Pharmaceuticals. R. SinhaRoy: Employee; Self; Regeneron Pharmaceuticals. C.A. Harris: Employee; Self; Regeneron Pharmaceuticals. B. Akinci: Advisory Board Member; Self; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals. Consulting Fee; Self; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals, AstraZeneca, Lilly USA, LLC, Merck, Novartis Pharmaceuticals, Novo Nordisk, Boehringer Ingelheim, Servier, Sanofi-Aventis. J. Altarejos: Employee; Self; Regeneron Pharmaceuticals. E.A. Oral: Consulting Fee; Self; Regeneron Pharmaceuticals, Aegerion Pharmaceuticals, Ionis Pharmaceuticals Inc., Third Rock Ventures, Rejuvenate Inc. Grant Recipient; Self; Regeneron Pharmaceuticals, Aegerion Pharmaceuticals, Ionis Pharmaceuticals Inc., Novo Nordisk, Rhythm pharmaceuticals, Fractyl Laboratories, GID Dynamics. Other; Self; Aegerion Pharmaceuticals. Background: Treatment of partial lipodystrophy patients is always challenging due to the lack of approved therapeutic options and the side effects of available medications. Here we report the long-term follow-up of a 21- year-old female patient with atypical partial lipodystrophy who developed neutralizing antibodies after treatment with metreleptin and was enrolled in a compassionate use protocol (IND No. 144013) with a leptin receptor agonist (mibavademab) after observing no benefit from setmelanotide (a melanocortin 4 receptor-agonist). Clinical case: The patient has been on compassionate use of mibavademab for 3 years and 6 months. Treatment-emergent adverse events were also followed. Treatment with mibavademab resulted in clinically significant metabolic benefits (reduction of fasting triglycerides < 500 mg/dL without the need for ongoing plasmapheresis). Previously, we reported the patient’s first 24-week response to treatment, showing a reduction of triglycerides from 1288 mg/dL to 344 mg/dl and a significant reduction in liver size and fat content (from 29.9% to 16.6%). We have now detailed the patient’s laboratory results over the last 2 years and 4 months, from week 60 to week 185. No new adverse events related to the study drug were reported during this period, and no concerning signals were found in her safety measurements. We noted changes in many laboratory parameters, including triglyceride levels, body weight, and glucose control. On average, the patient’s triglyceride levels has remained stable. However, liver size progressively reduced until week 36 of follow-up. Additionally, liver fat content decreased to 7.9% at week 52 and has remained stable since then. AST decreased by 24.3 IU/L, while ALT levels dropped by 17.7 IU/L. Hepatic stiffness score further decreased from 8.6 kPa to 5.1 kPa at week 104 and has remained stable thereafter. There were some fluctuations in HbA1c level as the patient has true autoimmune diabetes and insulin dependance and utilizes an insulin pump. Nadir HbA1c was 7.2% at 28 weeks of therapy. The patient regained 3.6 kg in body weight from week 24 to week 185 while maintaining good physical function and control of her chronic pain. Conclusion: Long-term treatment with mibavademab maintained initial substantial clinical benefit by improving the metabolic abnormalities in this patient while also preserving good physical function and control of chronic pain syndrome. This compassionate-use experience represents the longest human exposure to mibavademab. The long-term follow-up supports the safety profile of the treatment. Presentation: Friday, June 16, 2023