In an open-label study, initiated by
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
"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
Additional Lipodystrophy Studies
Two separate case studies from Michigan Medicine and led by
"This case suggests an association between the underlying disease and the risk of lymphoma," concluded authors Nazanene Esfandiari, M.D.,
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
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
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.
Amanda Murphy, Director, Investor Relations & Corporate Communications Novelion Therapeutics857-242-5024 firstname.lastname@example.org
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