Metreleptin and Lipodystrophy Data Presented at the Annual Meeting of the Endocrine Society

VANCOUVER, British Columbia & CAMBRIDGE, Mass., April 04, 2017 (GLOBE NEWSWIRE) — Novelion Therapeutics Inc. (NASDAQ:NVLN) (TSX:NVLN), a biopharmaceutical company dedicated to developing new standards of care for individuals living with rare diseases, today announced the presentation of four separate data presentations by academic researchers investigating metreleptin and lipodystrophy-related diseases at the annual meeting of the Endocrine Society, ENDO 2017, taking place in Orlando, April 1-4.  

In an open-label study, initiated by Elif Oral, M.D., Associate Professor of Medicine, Michigan Medicine, to predict the response to metreleptin treatment based on baseline leptin levels among 23 patients with partial lipodystrophy-associated NASH (nonalcoholic steatohepatitis, or fatty liver), the study team reported patients with a lower baseline leptin level appeared to have a higher response rate after one year of treatment with metreleptin. Metreleptin is a recombinant, synthetic analog of the naturally occurring hormone leptin.  The study was funded by National Institutes of Health and study drug (metreleptin) was provided by Novelion Therapeutics’ subsidiary.

Of the 23 patients enrolled in the study, 22 were treated with at least one dose of metreleptin at baseline. Of these 22 patients, the mean age was 41, and 17 were female and 5 were male. The primary endpoint of the study was the total NASH score from a liver biopsy, with related NAS (non-alcoholic fatty liver disease score) as a supportive endpoint. NASH measures hepatic steatosis with inflammation, ballooned hepatocytes, and/or fibrosis. There were secondary measures that included HbA1c, triglycerides, body fat and body composition.

Of the 18 patients who completed treatment at one year, NASH scores improved from 6 at baseline to 5 at 12 months (p=0.0079). NAS scores also improved from a mean baseline of 5 to 4 at 12 months (p=0.0002). Among patients who experienced a treatment response (n=9), the mean decrease in NAS scores was 2 (p=0.0047). This degree of improvement in the scores without a significant change in fibrosis has only been observed in patients with NASH not associated with lipodystrophy who experienced greater than 10 percent weight loss. Those who experienced a treatment response had a lower mean baseline leptin level of 14.5 ng/mL vs. non-responders whose average leptin level at baseline was 25 ng/mL.

While there were clinically important reductions in both glucose and lipid levels in subgroups of the patients, the differences noted in the entire cohort did not attain statistical significance.

The most frequently reported adverse events in the study occurring in more than 20 percent of patients were: upper respiratory infections, hypoglycemia, and diarrhea.

“Fatty liver is a common metabolic disturbance seen in patients with lipodystrophy. The underlying metabolic disturbances seen in patients can be difficult to manage with traditional therapies. Investigational studies improve our understanding of how baseline leptin levels can be used in patients with partial lipodystrophy-associated NASH to assess response to treatment with metreleptin,” said Dr. Oral, who was the principal investigator in the study.

“The liver disease at baseline is quite remarkable among the patients in this study, which showed a significant degree of inflammation and fibrosis, even in the absence of liver test abnormalities. This highlights the importance of screening for this complication,” added Nevin Ajluni, M.D., assistant professor of medicine at Michigan Medicine and the presenting author of the study.

Additional Lipodystrophy Studies

Researchers in Brazil presented a case study of a 22-year-old woman who presented with changed appearance due to abnormal subcutaneous fat redistribution. She had severe insulin resistance and had been treated for type 2 diabetes mellitus since age 10. The patient had been diagnosed with metabolic syndrome and type 2 diabetes mellitus. Upon examination, ultrasonography showed fatty and enlarged liver, and an enlarged spleen. Twenty-four relatives were screened and features of Dunnigan familial partial lipodystrophy were evident in 8 of 14 female relatives, suggesting the importance of screening family members to differentiate between metabolic syndrome and inherited forms of partial lipodystrophy.

Two separate case studies from Michigan Medicine and led by Dr. Oral were also highlighted. One case described a 33-year-old woman who was diagnosed with stage IV panniculitis-like T-cell lymphoma. Subsequent to her successful treatment for lymphoma, she presented with loss of adipose tissue with muscular prominence, high triglycerides and diabetes leading to a diagnosis of acquired generalized lipodystrophy (AGL).

“This case suggests an association between the underlying disease and the risk of lymphoma,” concluded authors Nazanene Esfandiari, M.D., Melvyn Rubenfire, M.D., and Dr. Oral. T-cell lymphoma has been reported in patients with AGL, both treated with metreleptin and in the absence of treatment.

The second case report described the development of AGL and juvenile dermatomyositis in a patient who is discovered to have a pathogenic missense variant on the LMNA gene, highlighting that some patients with seemingly AGL may have an underlying genetic defect.

“This latter case highlights the challenges of differentiating between genetic vs. acquired forms of lipodystrophy and suggests that the previously known relationship of juvenile dermatomyositis and AGL may be linked through genetic predispositions,” said Shafaq Khairi, M.D., the presenting author.  

About Lipodystrophy

Lipodystrophy syndromes (LD) are ultra-rare disorders characterized by the irreversible loss of adipose tissue. In patients with lipodystrophy syndromes, levels of leptin are often very low. Leptin is a naturally occurring hormone produced in adipose tissue and is an important regulator of energy homoeostasis, fat and glucose metabolism, reproductive capacity, and other diverse physiological functions.

With generalized lipodystrophy, the loss of fat affects the whole body. With partial lipodystrophy, the loss of fat typically occurs in the arms, legs, head and trunk regions, while accumulation of fat may occur in other areas of the body, including the neck, face and intra-abdominal regions. Metreleptin is approved in the U.S. to treat generalized lipodystrophy and is not approved to treat partial lipodystrophy.


MYALEPT® (metreleptin) for injection is a leptin analog indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. LIMITATIONS OF USE: The safety and effectiveness of MYALEPT for the treatment of complications of partial lipodystrophy or for the treatment of liver disease, including nonalcoholic steatohepatitis (NASH), have not been established. MYALEPT is not indicated for use in patients with HIV-related lipodystrophy. MYALEPT is not indicated for patients with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of generalized lipodystrophy.

Anti-metreleptin antibodies with neutralizing activity have been identified in patients treated with MYALEPT. T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with MYALEPT. For more detailed information, please see additional Important Safety Information and the Prescribing Information, including boxed warning, for MYALEPT. 

MYALEPT is available only through a restricted program called the MYALEPT REMS PROGRAM.

About University of Michigan, Metabolism, Endocrinology and Diabetes Division

The University of Michigan, Metabolism, Endocrinology and Diabetes Division and Brehm Center for Diabetes collectively house a major referral for the study of lipodystrophy syndromes. For more information, contact Adam Neidert at (734) 615-0539.

About Novelion Therapeutics

Novelion Therapeutics is a biopharmaceutical company dedicated to developing new standards of care for individuals living with rare diseases. The company seeks to advance its portfolio of rare disease therapies by investing in science and clinical development. Novelion has a diversified commercial portfolio through its indirect subsidiary, Aegerion Pharmaceuticals, Inc. (Aegerion), which includes MYALEPT® and JUXTAPID®, and is also developing zuretinol acetate for the potential treatment of inherited retinal disease caused by underlying mutations in RPE65 or LRAT genes. 


Amanda Murphy, Director, Investor Relations & Corporate Communications
Novelion Therapeutics