Data presented at the 59th Annual
American Academy of Dermatology (AAD) meeting support the further study of the
efficacy and safety of ASM 981 (pimecrolimus) oral tablet in the treatment of
adult patients with moderate to severe chronic plaque psoriasis. An ascomycin
macrolactam, ASM 981 is a selective inflammatory cytokine inhibitor that is
being developed by Novartis Pharmaceuticals Corporation specifically for the
treatment of inflammatory skin diseases.
"The findings for oral ASM 981 are encouraging as there is a need for a
safer treatment option for patients with moderate to severe plaque psoriasis,"
said Ken Washenik, MD, PhD, Director of Dermatopharmacology, New York
University School of Medicine. "Patients within this spectrum of disease
severity can be more challenging to treat, particularly given the extensive
range of side effects for currently available treatments. Knowing that a
patient may no longer have to face reactions from nausea to high blood
pressure, as seen with current treatments, ASM 981 may offer an exceptional
new possibility for long-term sufferers."
The randomized, double-blind, placebo-controlled pharmacokinetic
study was conducted to assess the safety, tolerability and efficacy of
orally-administered ASM 981 in patients with moderate to severe chronic plaque
psoriasis. The study examined 50 patients (80 percent on ASM 981, 20 percent
on placebo) across five consecutive increasing-dose groups for a total of four
weeks. Each group's dosing remained constant, with the respective dose levels
of ASM 981 at 5 mg OD (once daily), 10 mg OD, 20 mg OD, 20 mg BID (twice
daily), and 30 mg BID.
A treatment effect was noted with all doses, with a substantial effect at
the 20 mg and 30 mg BID dosings. This was measured by reduction of the
severity and extent of the signs of the disease. A 60 percent (20 mg BID) and
75 percent (30 mg BID) reduction was seen by week 4, as compared to a 4
percent reduction for placebo. The adverse event profile for ASM 981 was
favorable at all dosages and no serious adverse events occurred. The most
frequently reported adverse event suspected to be related to ASM 981 was
transient mild to moderate feeling of warmth not associated with flushing or
any changes in vital signs. The study showed no clinically significant change
in any safety parameter including physical examination, blood pressure, ECG,
blood chemistries, blood glucose tolerance tests, and three different renal
Psoriasis is a chronic skin disease from which more than 7 million people
in the United States suffer, according to the National Psoriasis Foundation.
Chronic plaque psoriasis occurs in 80 percent of patients with psoriasis. It
is a condition, which results in patches of thick, red skin covered with flaky
white or silvery scales. These patches, sometimes referred to as plaques, may
itch and burn. They occur on the elbows, knees, scalp, lower back, face,
palms, and may also affect other sites including the fingernails and
Approximately 20 to 25 percent of psoriasis sufferers have moderate to
severe disease. While varied options for treating moderate to severe
psoriasis do currently exist, not all are orally administered, all carry the
risk of short- and long-term side effects and many are inconvenient to use.
Worrisome side effects of current available therapies to treat moderate to
severe psoriasis may include liver damage, kidney damage, birth defects, high
blood pressure, and an increased risk of skin cancer.
According to Alice Gottlieb, MD, PhD, WH Conzen Chair in Clinical
Pharmacology, Professor of Medicine, Director, Clinical Research Center at
UMDNJ-Robert Wood Johnson Medical School, "Having psoriasis can generate
feelings of frustration, despair, and low self-esteem. Having a new agent
that is performing well in early clinical trials is promising, and the fact
that it is an oral formulation is particularly encouraging given the low
compliance rates among adult sufferers with topical treatments and the
toxicity of currently available oral therapies."
Additional studies of ASM 981 tablets are underway to examine its efficacy
in treating other skin diseases including atopic dermatitis.