Ligand's ONTAK Shows Potential to Treat Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma and Graft-Versus-Host Disease, Five Abstracts from ASH Meeting Demonstrate In Phase II Study, ONTAK Reduces CLL in Blood Cells, Lymph Nodes and Bone Marrow
SAN DIEGO, Dec 9, 2002 (BUSINESS WIRE) -- Ligand's ONTAK(R) (denileukin
diftitox) may benefit patients with chronic lymphocytic leukemia (CLL), B- and
T-cell non-Hodgkin's lymphoma (NHL) and graft-versus-host disease (GVHD) after
allogeneic hematopoietic stem cell transplantation, according to five abstracts
presented or published at the 44th annual meeting of the American Society of
Hematology, underway now in Philadelphia.
"These clinical studies add to the growing body of evidence suggesting that
ONTAK, which is approved to treat cutaneous T-cell lymphoma, may have benefits
for patients with other hard-to-treat cancers and serious compromise of the
immune system," said Andres Negro-Vilar, M.D., Ph.D., Ligand's senior vice
president for research and development and chief scientific officer. "We are
particularly excited about ONTAK's potential in refractory CLL, and plan to
begin a company-sponsored, large-scale Phase II study next year."
ONTAK Reduces CLL Blood Cells in Nine of 10 Fludarabine-Refractory Patients,
Shrinks Lymph Nodes in Six of 10
In ASH abstract 5020, researchers from Wake Forest, Louisville and Northwestern
reported interim results from their Phase II study of ONTAK in patients with
fludarabine-refractory, CD25-positive, B-cell CLL. Eighteen patients had been
treated with ONTAK when the abstract was submitted. They had received a mean of
four prior treatments, and 10 of them had advanced (Rai stage four) disease.
In the study, nine of 10 patients who received at least three courses of ONTAK
experienced reductions in peripheral CLL cells, with three of these patients
showing reductions of at least 99%. In addition, six of 10 patients showed
reductions in the diameter of their cancerous lymph nodes, with one patient
showing an 80% reduction. One of 12 patients showed a partial remission, with
80% node shrinkage and 100% clearance of CLL cells from bone marrow.
In the study, the side effects of ONTAK were similar to those reported
previously, including transient elevated transaminases, fever, asthenia,
hypoalbuminemia, nausea, vomiting, myalgias, rash, anorexia, vascular leak
syndrome, and elevated CPK.
"These results are encouraging, especially since there are few effective drugs
to treat refractory CLL patients," said lead author Arthur Frankel, M.D.,
professor of medicine and cancer biology at Wake Forest. "To elucidate the
activity of ONTAK further, we intend to investigate combination therapy with
Targretin(R) (bexarotene) to enhance IL-2 receptor expression and drug
sensitivity."
ONTAK Benefits Half of Patients with Relapsed or Refractory NHL
In ASH abstract 1405, scientists from the M.D. Anderson Cancer Center in Houston
reported results from their Phase II study of ONTAK in patients with relapsed or
refractory B- and T-cell NHL, most of whom had undergone multiple prior
treatments. The researchers were particularly interested in whether the efficacy
of ONTAK related to the degree of CD25 expression by tumor cells. CD25 is a
subunit of the IL-2 receptor, which is commonly expressed on the surface of
lymphoma cells.
Thirty-one patients entered the study, 25 of whom were available for response
evaluation. One patient had a complete response, four had partial responses, and
eight had stable disease, indicating that ONTAK benefited 52% of study patients
(13 of 25) overall. ONTAK was well tolerated in the study, with the majority of
side effects being mild to moderate and transient. Adverse events that occurred
in more than 20% of patients were fatigue, sensory changes, rash and nausea.
"These results demonstrate that ONTAK has activity in CD25-positive, B- and
T-cell NHL, as well as in tumors with low or non-detectable CD25 expression,"
said lead author Nam Dang, M.D., Ph.D., assistant professor of medicine at the
M.D. Anderson Cancer Center. "ONTAK was well tolerated at the dosing schedule
tested, although other doses may help enhance activity with tolerable side
effects."
ONTAK Improves GVHD in Seven of Nine Steroid-Refractory Patients
In ASH abstract 1638, researchers from the Dana-Farber Cancer Institute, Brigham
and Women's Hospital, the New England Medical Center and Ligand reported
preliminary results from a pilot dose-finding study to assess the safety and
efficacy of ONTAK in patients with steroid-refractory acute GVHD after
allogeneic hematopoietic stem cell transplants.
Ten patients had been treated when the abstract was submitted: two had grade II
GVHD, six had grade III GVHD, and two had grade IV GVHD. Nine of the patients
were able to be evaluated for GVHD response. Of these nine patients, three had
complete resolution of GVHD by day 28 of the study and four had partial
responses, defined as minimal one-grade improvement in one affected organ. The
overall response rate was 78% (seven of nine patients).
"Our preliminary results suggest that ONTAK was well tolerated by recipients of
allogeneic stem cell transplants, and had therapeutic activity for the treatment
of steroid-refractory GVHD," said Vincent Ho, M.D., instructor of medicine at
the Dana-Farber Cancer Institute and Harvard Medical School. "Enrollment in the
study continues, and the optimal dosing schedule remains to be determined."
A separate, in vitro study of ONTAK in GVHD is scheduled to be presented by Duke
scientists in a poster session from 5:15 to 6:45 p.m. Eastern Time today. The
study, ASH abstract 3299, is entitled "Alloreactive T Cells are Depleted by
Trimetrexate and IL-2 Immunotoxin in Synergy from PBSC and Umbilical Cord Blood
Grafts."
ONTAK Well Tolerated by Two ALCL Patients, One Shows Partial Response
In ASH abstract 4772, physicians from the University of Louisville, SUNY and
Wake Forest reported treating two patients with primary systemic T-cell
anaplastic large cell lymphoma (ALCL) whose disease had relapsed following
autologous stem cell transplants and other aggressive treatments. ALCL is the
second most common T-cell lymphoma and represents approximately 2% of all adult
NHL. In general, the prognosis for systemic ALCL is poor, and therapy is not
well defined.
Both patients were given one cycle of ONTAK. The authors conclude that in these
patients, ONTAK did not produce any infusion-related, hematologic or organ
toxicity. They also note that ONTAK produced an objective clinical response in
one patient with abnormal liver function, a situation where the use of other
cytotoxic drugs would have been prohibitive.
About ONTAK
In February 1999, the U.S. Food and Drug Administration granted Seragen, Inc., a
wholly owned subsidiary of Ligand, marketing approval for ONTAK for the
treatment of patients with persistent or recurrent CTCL whose malignant cells
express the p55 (CD25) component of the IL-2 receptor.
Full prescribing information for Ligand's products can be obtained in the United
States from Ligand Professional Services by calling 800-964-5836, or on Ligand's
internet site at www.ligand.com.
Full abstracts for the five ONTAK studies discussed in this news release are
available on the ASH internet site at www.hematology.org. |
