Data Presented At AAD Show Low Doses of ONTAK Induce Responses in Moderate-to-Severe Plaque Psoriasis.

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SAN DIEGO--(BW HealthWire)--March 5, 2001

Additional Data Presented Show Responses for Targretin(R) Gel as

First-Line Treatment for Cutaneous T-Cell Lymphoma and for

Panretin(R) Gel in Classical Kaposi's Sarcoma 

Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) today announced that investigators presented results of a pilot study demonstrating responses with ONTAK(R) (denileukin diftitox) with low dose schedules in patients with moderate-to-severe plaque psoriasis. These results and results from two studies of Targretin(R) gel and Panretin(R) gel were presented at the 59th Annual Meeting of the American Academy of Dermatology (AAD) in Washington, D.C.

"We are extremely pleased that this study confirms the anti-psoriatic activity of ONTAK with low dose schedules," said Steven D. Reich, M.D., Senior Vice President of Clinical Research at Ligand. "The high dose levels of ONTAK used to clear malignant cells in patients with CTCL are not required to treat patients with psoriasis. Beneficially, the toxicity profile of ONTAK at these lower doses is more suitable to patients with psoriasis, a disease that is not generally life-threatening. Further research will be required to determine the optimal dosing regimen in patients with psoriasis and other related T-cell mediated diseases such as rheumatoid arthritis."

Six patients with moderate-to-severe plaque-type psoriasis received ONTAK at a dose of 5 mcg/kg/day, as a 15-minute infusion administered on either one day every other week or for three consecutive days every other week. Patients were scored for disease severity before and during the eight-week study period, and samples of peripheral blood and skin biopsies were obtained for analysis.

All six patients completed this pilot study of ONTAK and achieved the protocol-defined response criteria of at least 30 percent decrease in Psoriasis Area and Severity Index (PASI) score at some point in the eight-week study. Two patients met the more stringent criterion of at least 50 percent reduction in PASI score.

Response rates were not significantly different between the two dosing regimens. Clinical improvements were seen as early as one to two weeks, with a median time to response of approximately 29 days. Adverse events were mild, with related adverse events occurring in more than one patient being fever, chills, and asthenia. This study was presented as abstract P518, "Denileukin Diftitox (DAB389IL-2) Improves Skin Lesions in Patients with Moderate-to-Severe Plaque Psoriasis," by lead author Brigitte Holder, M.D., Laboratory for Investigative Dermatology, The Rockefeller University.

Targretin Gel Produces Overall Response Rate of 75 Percent in Patients with Untreated, Early-Stage CTCL

Results from 12 patients (a subset of a 67-patient study) in a multicenter, dose-ranging, Phase I-II trial demonstrated that patients with untreated cutaneous T-cell lymphoma (CTCL) respond to Targretin (bexarotene) gel. Responses were evaluated every four weeks by a Physician's Global Assessment and a Composite Assessment of clinical signs and symptoms that required at least 50 percent improvement for at least four weeks. Overall response rate was 75 percent (nine of twelve) in these treatment-naive patients.

Complete responses (100 percent clearing) were seen in 33 percent of treatment-naive patients (4/12): two patients with Stage IA, one with Stage IB, and one with Stage IIA. Partial responses (at least 50 percent clearing) were seen in 42 percent of patients (5/12), all with Stage IA disease. Earliest time to onset of response was 29 days, with a projected median of 92 days. Responses were durable, with 33 percent of patients (3/9) relapsing over a median of 484 days. Adverse events were predominantly limited to the site of application (rash, pruritus, pain, and skin irritation) and were generally mild to moderate in severity. There were no drug-related serious adverse events, although one patient withdrew due to a mild rash. This study was presented in abstract P204, "Efficacy and Safety of Bexarotene Gel in Patients with Previously Untreated CTCL," by lead author Debra Breneman, M.D., University of Cincinnati.

Patient with Classical Kaposi's Sarcoma Responds to Panretin Gel

A case report of an 83-year-old woman presenting with multiple classical Kaposi's sarcoma (KS) lesions found that Panretin (alitretinoin) gel 0.1% provided local control of classical KS cutaneous lesions. The patient had previous unsuccessful treatment with excision, laser, and cryosurgery.

The patient treated her lesions with Panretin gel twice daily. After five months, all treated lesions demonstrated 90 to 100 percent resolution. After seven and a half months of treatment, no lesions were present on examination. The patient presented with three new lesions in untreated areas at 11 months of treatment, and they completely resolved with subsequent treatment with Panretin gel. The patient experienced mild burning and a mild, self-limited dermatitis during treatment; otherwise, no significant adverse events were observed. This case report is abstract P465, "Successful Treatment of Classical Kaposi's Sarcoma with Alitretinoin Gel 0.1," by Greg Morganroth, M.D., Orchard Creek Medical Center.

ONTAK, Targretin gel, and Panretin gel

ONTAK was approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with persistent or recurrent CTCL whose malignant cells express the CD25 component of the IL-2 receptor. Targretin gel is approved as a topical treatment of cutaneous lesions in patients with early-stage (TNM Stage IA and IB) CTCL who have refractory or persistent disease after other therapies or who have not tolerated other therapies. Panretin gel is approved for the topical treatment of cutaneous lesions in patients with AIDS-related KS.

Ligand Pharmaceuticals Incorporated

Ligand Pharmaceuticals Incorporated discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, skin diseases, and men's and women's hormone-related diseases, as well as osteoporosis, metabolic disorders and cardiovascular and inflammatory diseases. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IRs) and Signal Transducers and Activators of Transcription (STATs).

Information contained in this press release which is not historical may be forward-looking. Forward-looking statements and actual results could differ materially from those described as a result of factors including, but not limited to the following. There can be no assurance that results of additional clinical trials of ONTAK, Targretin gel or Panretin gel will confirm results of earlier clinical trials; that ONTAK will be approved for additional indications; or that any Ligand product will be accepted by patients and physicians. Additional information concerning these and other factors affecting Ligand's business can be found in press releases as well as in Ligand's public periodic filings with the Securities and Exchange Commission, which are available via Ligand's web site at www.ligand.com. Ligand disclaims any intent or obligation to update any forward-looking statements beyond the date of this release.

Panretin(R) and Targretin(R) are registered trademarks of Ligand Pharmaceuticals Incorporated. ONTAK(R) is a registered trademark of Seragen, Inc., a wholly owned subsidiary of Ligand. Full prescribing information for Ligand's products may be obtained by calling Ligand Professional Services at 800-964-5836, or, in Europe, Ligand Pharmaceuticals International, Inc., at [phone].

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