Here's LGND's press release on their three advanced trials for Targretin for CTCL:
Ligand To Launch Three Pivotal Trials With Targretin(TM) (LGD1069) Oral And Topical
SAN DIEGO, Aug. 22 /PRNewswire/ -- Ligand Pharmaceuticals Inc.
(Nasdaq: LGND) today announced that it reached agreement with the U.S. Food
and Drug Administration (FDA) on trial design and will launch three Phase
II/III pivotal clinical trials for the treatment of cutaneous T-cell lymphoma
(CTCL) with Targretin(TM) (LGD1069), a retinoid subtype receptor selective
agonist discovered and developed by Ligand scientists. During meetings with
the FDA in August, the Company and the FDA reached agreement on the design and
endpoints for two Phase II/III trials to evaluate orally administered
Targretin capsules, and one Phase III trial to study Targretin gel for the
topical treatment of CTCL.
"We presented safety and activity data to the FDA on both Targretin oral
capsules and Targretin topical gel. The data showed that Targretin oral
capsules appear to be well-tolerated over a very broad dose range up to 1000
mg/m2/day in 119 advanced cancer patients in Phase I/II studies. In our
interim assessment of ongoing Phase I/II studies, data showed that at least 11
of 30 CTCL patients (37%) treated topically with Targretin gel had complete or
partial responses," said Steven D. Reich, M.D., Ligand Senior Vice President,
Clinical Research. "Based upon these data we determined, with the FDA, that
both formulations should be evaluated further in open label pivotal trials to
determine efficacy in CTCL and to accumulate the data necessary to support NDA
submissions."
Based on input from the FDA, the initiation of three independent open
label pivotal studies over the next several months is planned. Two Phase
II/III studies are to be conducted with Targretin oral capsules: one study
will treat refractory or persistent early-stage CTCL, and the other study will
treat refractory advanced CTCL. Each study will involve 60 patients. The
third pivotal trial is to study the efficacy of Targretin topical gel in 60
refractory or persistent early stage CTCL patients.
"These three trials, in addition to the pivotal Phase III trial we are
conducting on behalf of Allergan Ligand Retinoid Therapeutics, Inc. with
Panretin(TM) (ALRT1057) Topical in Kaposi's sarcoma, mean that Ligand's
clinical research group is conducting four early registration, pivotal trials
on three distinct products, moving the Company another step closer to
registration and commercialization," said David E. Robinson, Ligand Chairman,
President and Chief Executive Officer.
Results of Phase I/II studies reported earlier this year indicated that
both formulations of Targretin have activity in the treatment of CTCL.
Treatment of CTCL with Targretin oral capsules resulted in clinical response
of two of nine patients. The time to earliest response was 15 and 22 days,
and duration of response was 12 and 19 weeks. Treatment of CTCL lesions
resulted in at least 11 of 30 (37%) of the Targretin topically treated
patients experiencing at least a 50% response based on the physicians' global
assessment. Of the 37% responders, 100% were still responsive at a median of
8+ weeks follow-up.
In addition to these early registration, pivotal CTCL trials, Targretin
Oral is in Phase IIb trials in patients with advanced lung cancer, head and
neck cancer, Kaposi's sarcoma and kidney cancer. In April, investigators
reported stabilization of disease in many lung cancer patients treated with
Targretin oral capsules. Ligand expects to review interim Phase IIb data for
treatment of lung cancer early next year.
Targretin(TM) (LGD1069) is a compound discovered by Ligand scientists
which selectively activates a subclass of retinoid receptors called retinoid X
receptors (RXRs) which play an important role in several cellular activities.
One of the most important of these activities is called programmed cell death,
or "apoptosis," a natural process by which the body rids itself of unwanted
cells.
Preclinical in vitro findings presented to the FDA and elsewhere have
demonstrated that Targretin's selective activation of the RXR family of
receptors induces apoptosis in a human promyelocytic cell line (HL-60) and in
the human cervical squamous cell line (ME 180). It induces apoptosis and
inhibits cell proliferation in the human myeloma cell line (RPMI 8226). And,
it inhibits cell proliferation of Kaposi's sarcoma, breast carcinoma, prostate
carcinoma and squamous cell carcinoma, all derived from human cell lines.
Preclinical in vivo findings presented to the FDA, indicated that
Targretin completely suppresses carcinogen-induced mammary tumors in the NMU
rat model with efficacy equal to or better than tamoxifen. It inhibits tumor
growth in the nude mouse xenograft model with two primary human squamous cell
tumors. It produces a dose dependent decrease in the volume of papillomas in
the Sencar mouse two-stage model of carcinogenesis. And, it possesses
antikeratinizing activity in the rhino mouse model with topical or oral
administration.
Ligand Pharmaceuticals Incorporated, founded in 1987, is a leader in gene
transcription technology, particularly intracellular receptor (IR) technology
and Signal Transducers and Activators of Transcription (STATs). Ligand has
applied IR and STATs technology to the discovery and development of small
molecule drugs to enhance therapeutic and safety profiles and to address major
unmet patient needs in cancer, women's health, skin diseases, osteoporosis,
cardiovascular and inflammatory disease.
This press release contains certain forward looking statements by Ligand
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: (a) that the clinical and preclinical results described herein will
be observed in patients; (b) that these or any products under development by
Ligand or any of its partners will receive approval from the U.S. Food and
Drug Administration or other authorities to market any of these products; (c)
that, if approved, there will be a market for the drugs; or (d) that interim
results will be predictive of any final results to be reached.
Targretin(TM) (LGD1069) is a trade mark of Ligand Pharmaceuticals
Incorporated.
Panretin(TM) (ALRT1057) is a trade mark of Allergan Ligand Retinoid
Therapeutics, Inc.
SOURCE Ligand Pharmaceuticals
CONTACT: Susan E. Atkins, Vice President, Corporate
Communications and Investor Relations of Ligand, 619-550-7687 |
