This article is more than 5 years old. Information may no longer be current.
FDA approves Myalept for treatment of lipodystrophy
Click Here to Manage Email Alerts
The FDA today approved metreleptin, in combination with diet, for the treatment of complications of leptin deficiency in patients with congenital generalized or acquired generalized lipodystrophy, according to a press release.
“Myalept is the first approved therapy indicated for treating the complications associated with congenital or acquired generalized lipodystrophy and provides a needed treatment option for patients with this orphan disease,” Mary Parks, MD, deputy director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, said in the release.
Metreleptin (Myalept, Amylin Pharmaceuticals) is an analog of the naturally occurring hormone leptin, which is made by fat tissue. Because patients with lipodystrophy, either congenital or acquired, have very little fat tissue, they also produce very little leptin, which regulates food intake and other hormones such as insulin.
The newly approved medication was evaluated in an open-label, single-arm study of 48 patients with congenital or acquired generalized lipodystrophy who also had diabetes, hypertriglyceridemia, and/or elevated levels of fasting insulin. The trial resulted in reductions in HbA1c, fasting glucose and triglycerides, according to the release. The most common adverse effects observed were hypoglycemia, headache, decreased weight and abdominal pain.
Myalept will only be available through the FDA’s Risk Evaluation and Mitigation Strategy (REMS) due to the risk of developing neutralizing antibodies and lymphoma seen in patients with lipodystrophy both treated and not treated with the drug.
“Under this REMS program, prescribers must be certified with the program by enrolling in and completing training. Pharmacies must be certified with the program and only dispense Myalept after receipt of the Myalept REMS Prescription Authorization Form for each new prescription,” the release stated.
The FDA also announced its requirement of seven postmarketing studies for Myalept, including a product exposure registry of patients, a study to assess immunogenicity and an assessment and analysis of spontaneous reports of serious risks related to use of the medication. There are also eight additional studies requested.
FDA approves Myalept to treat rare metabolic disease.
Perspective
Back to Top
Abhimanyu Garg, MD
I’ve been evaluating patients with lipodystrophy for more than 25 years and we’ve made tremendous progress in understanding the molecular genetic basis for this rare syndrome and also in understanding why they develop metabolic complications of insulin resistance, such as premature diabetes, severe hypertriglycemia and hepatic steatosis. It is one thing to understand the pathogenesis of the disorder, but it’s another thing to help these patients with a novel treatment which can improve the metabolic derangements.
Before we began clinical trials with metreleptin about 14 years ago, we were using conventional therapies to treat these patients.
Even with low doses of metreleptin, we can normalize their blood leptin levels, resulting in marked improvements in diabetes, hypertriglyceridemia and hepatic steatosis.
Many of the patients with generalized lipodystrophy who once took thousands of units of insulin daily don’t require it upon initiating leptin replacement therapy; or we can now control them on a reduced dose of insulin. Some of them don’t need lipid-lowering therapies anymore and we definitely see a reduction in liver fat and size as well, indicating that their hepatic steatosis is improving.
Overall, after almost 14 years, I’m very happy for my patients that the therapy is finally approved. Anybody affected with generalized lipodystrophy can now see benefits with leptin hormone replacement therapy.
Perspective
Back to Top
Thomas B. Repas, DO, FACP, FACE, CDE
The U.S. Food and Drug Administration recently approved Myalept (metreleptin for injection) for the treatment of generalized lipodystrophy. Metrelepin is an analog of leptin and is the first medication to be approved for this indication. Metrelepin is only approved for the treatment of congenital or acquired generalized lipodystrophy, not for the much more common HIV-associated lipodystrophy or partial lipodystrophies. It is also not approved for the treatment of obesity or other metabolic disease, including type 2 diabetes mellitus and hypertriglyceridemia.
Lipodystrophies are rare syndromes associated with complete or partial loss of subcutaneous fat tissue. In general, lipodystrophy is classified into subtypes depending on whether the fat loss is complete or partial and whether the syndrome is congenital or acquired. Metabolic abnormalities are common, including insulin resistance, type 2 diabetes, fatty liver disease, PCOS and hypertriglyceridemia.
Congenital and acquired generalized lipodystrophy tend to be diagnosed at younger ages and present with more severe metabolic abnormalities. They are both extremely rare. There have been only about 250 cases of congenital generalized lipodystrophy reported and less than 100 cases of acquired generalized lipodystrophy. In comparison, it is estimated that there are over 100,000 cases of HIV-associated lipodystrophy in the US alone.
Until the approval of Myalept, the only available treatment options besides dietary and lifestyle modification were medications to treat the underlying metabolic abnormalities including anti-diabetes and lipid-lowering medications. Because the metabolic derangements of generalized lipodystrophy tend to be severe, and less likely to respond to standard therapies, it is good to have a new drug available to treat these rare orphan diseases.
The initial open-label, single-arm study of 48 patients showed improvements in HbA1c, fasting glucose, and triglycerides. Of concern, neutralizing antibodies were reported, as well as T-cell lymphoma in patients with acquired generalized lipodystrophy, both treated and not treated.
Because of this, the FDA is requiring additional studies and for now, metreleptin will only be available only through a Risk Evaluation and Mitigation Strategy (REMS) Program. Prescribers and pharmacies must be certified through this REMS program before they can prescribe and dispense this drug.
Due to the rarity of these two syndromes, I do not envision this medication will be prescribed very often. As an endocrinologist and lipidologist, I have a number of patients with lipodystrophy. At the present time, however, I only have a single patient with acquired generalized lipodystrophy who could potentially be eligible for treatment.
The REMS program requirements may be somewhat of a barrier. However, if there is a patient who truly could benefit, I suspect that most clinicians with expertise in lipodystrophy would be willing to consider this medication, given how challenging it can be to treat the severe metabolic abnormalities of some of these patients.
A question for which we do not have the answer to: could this drug (or a similar drug without the adverse effect concerns) ever become an option for the treatment of other lipodystrophies or for that matter for the treatment of individuals with metabolic disease but without lipodystrophy? The FDA felt that submitted data was insufficient to show benefit for the treatment of other patient groups. Only with time and more research will we know.
For more information:
Click Here to Manage Email Alerts