metreleptin (Myalepta)

following a full submission assessed under the ultra-orphan process:

Indication under review: as an adjunct to diet as a replacement therapy to treat the complications of leptin deficiency in lipodystrophy (LD) patients with:

• confirmed congenital generalised LD (Berardinelli-Seip syndrome) or acquired generalised LD (Lawrence syndrome) in adults and children 2 years of age and above.
• confirmed familial partial LD or acquired partial LD (Barraquer-Simons syndrome), in adults and children 12 years of age and above for whom standard treatments have failed to achieve adequate metabolic control.

Key Points:

• Lipodystrophy is a very rare, serious and heterogeneous, inherited or acquired condition. It is characterised by variable loss of adipose tissue and is associated with severe metabolic abnormalities, which can result in significant morbidity and mortality in affected patients.
• After 12 months of treatment in a single-arm, open-label study, metreleptin significantly improved the co-primary outcomes of change from baseline in HbA1c and percent change in fasting triglycerides.
•  The co-primary outcomes are surrogate outcomes of metabolic control and there are no data on the effect of metreleptin on clinically relevant longer term complications.
• There are no controlled data and limitations in the indirect comparison with supportive care make the size of the metreleptin treatment effect unclear. Furthermore, evidence was confounded by a lack of restriction or control of background diet and supportive treatment, which may have affected metabolic control.
• No patient-reported outcomes or quality of life data were collected during the main study and the impact of metreleptin on these outcomes is unknown.
• The cost of metreleptin in relation to its health benefits remains high and the evidence used in the economic model is highly uncertain; including no direct evidence on long term effectiveness, impacts on morbidity and mortality, no utility evidence for patients, and limited primary resource use data for a population of lipodystrophy patients.

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From 7 September 2023 metreleptin (Myalepta) can be prescribed within the ultra-orphan pathway while further evidence on its effectiveness is generated. At the end of the data collection period the company will provide an updated submission for reassessment to allow a decision on its routine use in NHSScotland.