Acthar in Treatment of Refractory Dermatomyositis and Polymyositis

Despite its FDA approval there is very limited data on its clinical effectiveness in PM and
DM. There was a recent study published in the peer-review journal Drug Design, Development
and Therapy on a retrospective case series evaluating Acthar in the treatment of PM and DM.
Acthar was administered to five patients who had previously failed multiple steroid and
immunosuppressant treatment regimens. The patients received injections of Acthar over the
course of 12 weeks or more. Improvement in PM and DM symptoms related to disease
exacerbations was seen in all five patients. Symptom improvements included increased muscle
strength, resolution of disease-related skin manifestations and improvements in the ability
to perform tasks associated with daily living. All of these patients tolerated the treatment
well with no significant side effects reported. The paper, "Treating refractory
dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case
series," was authored by Dr. Todd Levine, M.D., Co-Director of the Neurophysiology
Department at Banner Good Samaritan Medical Center, Assistant Professor at the University of
Arizona in Neurology, and Member of Phoenix Neurological Associates.

H.P. Acthar® Gel, or Acthar, is a prescription medication containing the hormone
adrenocorticotropin (hormone produced and secreted by the anterior pituitary gland), also
known as ACTH. H.P. Acthar Gel is a highly purified preparation of adrenocorticotropic
hormone (ACTH) in a gel that is designed to provide extended release of the ACTH following
injection. Acthar was originally approved by the FDA in 1952. It is approved for use in 19
different conditions including dermatomyositis and polymyositis.

Acthar is designed to provide a prolonged release of the medication after it is injected.
Acthar is not a steroid; it works by helping your body produce its own natural steroid
hormones, such as cortisol, corticosterone, and aldosterone. Acthar is an injection that is
given intramuscularly (into the muscle). Subjects enrolled in the study will be asked to
self administer Acthar two times per week. Subjects will be provided training by the
principal investigator on how to perform the self injections.

Inclusion Criteria:

- Definite or probable polymyositis (PM) or dermatomyositis (DM) by Bohan and Peter
criteria.

- PM patients must either possess a myositis-associated autoantibody or undergo
adjudication for confirmation of the PM diagnosis by consensus of two experts to
ensure non-PM patients are not enrolled. This step is necessary since there are
well-known mimics of PM.

- Age ≥ 18 years.

- Active myositis as defined by baseline Manual Muscle Testing (MMT-8) no greater than
125/150 and at least 2 additional CSM meeting the criteria stipulated below:

1. Patient global with a minimum value of 2.0 cm on a 10 cm visual analog
scale(VAS)

2. Physician global with a minimum value of 2.0 cm on a 10 cm VAS scale

3. Health Assessment Questionnaire (HAQ) disability index with a minimum value of
0.25

4. Elevation of at least one of the muscle enzymes [which includes creatine kinase
(CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and
aspartate aminotransferase (AST)] at a minimum level of 1.3 x the upper limit of
normal.

5. Global extramuscular disease activity score with a minimum value of 1.0 cm on a
10 cm VAS scale [this measure is the physician's composite evaluation and is
based on assessments of activity scores on the constitutional, cutaneous,
skeletal, gastrointestinal, pulmonary and cardiac scales of the Myositis Disease
Activity Assessment Tool (MDAAT)].

- To ensure that we can enroll active DM patients with a severe rash who may not meet
the MMT-8 criterion noted above, we propose additional enrollment criteria such that
the International Myositis Assessment and Clinical Studies (IMACS) definition of
improvement (DOI) can potentially be met:

1. Cutaneous VAS score on MDAAT > 3 cm on a 10 cm VAS scale, and

2. At least 3 of the above 5 (a through e under 4.) criteria.

- Refractory myositis is defined by active disease despite an adequate glucocorticoid
trial (> 2 months of usual glucocorticoid therapy or intolerance to such therapy)
and/or ≥ 1 conventional immunosuppressive agent (e.g. methotrexate, azathioprine,
tacrolimus, cyclosporine, mycophenolate mofetil, IVIG, anti-TNF or rituximab) for a
reasonable dose and duration (> 3 months or intolerance to therapy). It is
recommended to enroll refractory patients failing (or intolerant to) both
glucocorticoids and at least 1 conventional immunosuppressive agent.

- If the enrolling physician is planning to continue current immunosuppressive agents
or glucocorticoids as concomitant therapy with Acthar gel during the trial, then
patient must be on a stable glucocorticoid and/or immunosuppressive dose 2 weeks
prior to visit 1. The patient should have been on that immunosuppressive medication
for at least 8 weeks (and at least 4 weeks for glucocorticoids) prior to visit 1.

- If the enrolling physician is planning to discontinue current immunosuppressive agent
or glucocorticoids, then following wash out period is required prior to visit 1.

- If previous concomitant medications were discontinued, the following wash out periods
are required prior to Visit 1

- Methotrexate -4 weeks

- Other IS agent (e.g. azathioprine, cyclosporine, tacrolimus, leflunomide,
mycophenolate mofetil) - 4 weeks

- IVIg or cyclophosphamide - 2 months

- rituximab -6 months

- infliximab or adalimumab -8 weeks

- glucocorticoids - 2 weeks

- etanercept -2 weeks

- anakinra -1 week

Exclusion Criteria:

- Juvenile DM or PM, myositis in overlap with another connective tissue disease, cancer
associated myositis, inclusion body myositis, or any other non immune-mediated
myopathy.

- Hypersensitivity to Acthar

- Severe cardiac or pulmonary involvement

- Severe muscle damage defined as a baseline global muscle damage score on the MDI
(Myositis Damage Index) of ≥ 5 cm on a 10 cm VAS.

- Patients with malignancy within 3 years of screening (except basal cell cancer or
squamous cell cancer of skin).

- Uncontrolled diabetes, hepatic or renal disease.

- Ongoing active or chronic infections.

- Pregnant or lactating females.

- For any medical or physical or socio-psychological reasons that PI feels would not
allow the subject to complete the study.