ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P586 | DOI: 10.1530/endoabs.63.P586

Real-world experience of generalized and partial lipodystrophy patients enrolled in the metreleptin early access program

Keziah Cook1, Anna Stears2, David Araujo-Vilar3, Ferruccio Santini4, Stephen O’Rahilly2, Giovanni Ceccarini4, Shruti Tibrewala1, Pamela Bradt5, Corinne Vigouroux6, Camille Vatier6 & David B Savage2

1Analysis Group, Menlo Park, CA, USA; 2University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK; 3University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain; 4University Hospital of Pisa, Pisa, Italy; 5Aegerion Pharmaceuticals, Cambridge, MA, USA; 6Sorbonne University, Reference Center of Rare Diseases PRISIS, Hospital Saint-Antoine, Paris, France.

Objective: To evaluate the real-world experience of patients with generalized (GL) and partial (PL) lipodystrophy initiating treatment with metreleptin as part of an early access program (EAP).

Methods: A retrospective data collection was conducted from four countries for patients enrolled in the EAP. A descriptive analysis was performed on selected patient characteristics, baseline organ impairments and complications, and response to metreleptin therapy, measured through changes in triglycerides (TG) and HbA1c.

Results: 53 lipodystrophy patients (GL, PL: 28, 25) were identified in four countries (France: 19, Italy: 3, Spain: 11, UK: 20). Average age at metreleptin initiation for GL and PL patients was 17.4 (SD: 14.9) and 38.6 (SD: 12.6) respectively. Among patients treated in France, Italy, and UK, 100% presented with organ impairments at baseline, including liver impairment (GL, PL: 100%, 100%), cardiovascular damage (24%, 44%), kidney impairment (35%, 20%) and pancreatitis (12%, 16%). 93% of patients had diabetes. Prior to treatment, 95% of GL patients and 71% of PL patients had TG >200 mg/dl and 78% of GL patients and 68% of PL patients had HbA1c >7%. Duration of patients’ metreleptin exposure varied, with a maximum of 14.7 years (mean 5.4, S.D.: 3.5). Following treatment for GL patients, mean % TG change was a decrease of 53% (P<0.001) and mean HbA1c change was a 1.9 percentage point decrease (P<0.001) between baseline and 12 months. By month 12, 50% of GL patients (vs 5% at baseline) achieved TG ≤200 mg/dl and 57% of patients (vs 22% at baseline) achieved HbA1c ≤7%. For PL patients, mean % TG change was a decrease of 21.5% (P<0.005) and mean HbA1c change was a 0.5 percentage point decrease (P<0.1). By month 12, 52% of PL patients (vs 29% at baseline) achieved TG ≤200 mg/dl with no change in the 32% at baseline that achieved HbA1c ≤7%. No new safety signals emerged as EAP data were integrated with existing safety data. In the clinical trial, the most frequent adverse reactions reported included decreased weight (17%) and mild occurrences of hypoglycaemia (14%); other adverse reactions affected <10%.

Conclusions: Response to metreleptin in real-world EAP patients was consistent with clinical trial experience for registration, which resulted in mean % TG decrease (GL, PL: 32.1, 37.4) and HbA1c percentage point decrease (GL, PL: 2.2, 0.9). Ongoing research is needed to further characterize the burden of lipodystrophy on patients and the impact of metreleptin.