Metreleptin was approved in the United States as adjunct to diet as replacement therapyto treat the complications of leptin deficiency in patients with congenital or acquiredgeneralized lipodystrophy in February 2014. The approval was based on results obtained in2 open-label, investigator-sponsored studies (Studies 991265 and 20010769) conducted atthe National Institutes of Health (NIH) to evaluate the safety and efficacy ofmetreleptin treatment in patients with lipodystrophy and 1 treatment IND(FHA101/MB002-002/MB002-002) conducted by Bristol-Myers Squibb on behalf of AstraZeneca(BMS/AZ) in patients with diabetes mellitus and/or hypertriglyceridemia related tolipodystrophy. These studies enrolled patients with lipodystrophy including bothgeneralized and partial lipodystrophy. Although the marketing authorization restrictedthe indication to patients with generalized lipodystrophy, meaningful clinical benefitwas achieved in a subset of patients with partial lipodystrophy, and these patients fromFHA101/MB002-002 form the basis of the request for ongoing treatment under expandedaccess.
Leptin is a naturally occurring hormone and an important regulator of energy homeostasis
and other diverse physiological functions. Circulating levels of leptin closely correlate
with the amount of adipose tissue present. Metreleptin, a recombinant analogue of human
leptin, is a 147-amino acid polypeptide that differs from the human leptin sequence by 1
additional amino acid, methionine, located at the amino-terminal end. Metreleptin has the
same physiological effects as leptin, including regulation of energy homeostasis and
metabolic function.
The patient group covered under this expanded access submission has demonstrated evidence
of clinical benefit from treatment with metreleptin in clinical study FHA101/MB002-002,
and needs expanded access to continue treatment without interruption.
New enrollment, subject to approval by the FDA, can be considered on a case-by-case
basis.
Drug: Metreleptin
Metreleptin open-label treatment
Other Name: MyaLept
Inclusion Criteria:
1. Signed Written Informed Consent
a) Before any program procedures are performed, the details of the program will be
described to the patient and the patient will be given a written informed consent
document to read. If the patient agrees to participate in the program, consent will
be indicated by signing and dating of the informed consent document in the presence
of program personnel.
2. Target Population
1. Ability to comply with visits and procedures required by program
2. Previously enrolled in study FHA101/MB002-002
3. Has physician-confirmed partial lipodystrophy and had evidence of benefit with
metreleptin treatment based on the following metabolic criteria demonstrated
within the last year of metreleptin treatment (if on treatment over 1 year)
from baseline values:
- TG reduction ≥ 30% OR
- HbA1c reduction ≥ 1% OR
- Decrease in insulin requirements ≥ 40% OR
- Decrease in episodes of pancreatitis OR
- Improvement in steatohepatitis OR
- Withdrawal of metreleptin led to marked worsening of metabolic parameters
3. Age and Reproductive Status
1. Male or female, over the age of 6 months
2. Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within
24 hours prior to the restart of study drug.
3. Women must not be breastfeeding
4. WOCBP must agree to follow instructions for method(s) of contraception for the
duration of treatment with metreleptin plus 5 half-lives of metreleptin plus 30
days (duration of ovulatory cycle) for a total of 6 months post-treatment
completion.
5. Men who are sexually active with WOCBP must agree to follow instructions for
method(s) of contraception for the duration of treatment with metreleptin plus
5 half-lives of the metreleptin plus 90 days (duration of sperm turnover) for a
total of 3 months post-treatment completion.
Exclusion Criteria:
1. Target Disease Exceptions
a) Has acquired lipodystrophy and clinically significant hematologic abnormalities
(such as neutropenia and/or lymphadenopathy)
2. Medical History and Concurrent Diseases
1. Has been diagnosed with generalized lipodystrophy
2. Has been diagnosed with HIV infection
3. Has a clinically significant medical condition that could potentially affect
the risk/benefit ratio for metreleptin treatment and/or the personal well-being
of the patient, as judged by the primary treating physician
4. Has known infectious liver disease
5. Has known allergies to E. coli-derived proteins or hypersensitivity to any
component of metreleptin treatment
3. Other Exclusion Criteria
1. Prisoners or patients who are involuntarily incarcerated.
2. Patients who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.
University of Michigan
Ann Arbor, Michigan, United States
Investigator: Elif A Oral, MD
Contact: 734-615-7271
eliforal@med.umich.edu
Investigator: Nevin A Ajluni, MD
Elif A Oral, MD
734-615-7271
eliforal@med.umich.edu
Adam H Neidert, MS
734-615-0539
aneidert@med.umich.edu
Elif A Oral, MD, Principal Investigator
University of Michigan