Investigational Targeted Therapy May Offer Progress for Non-Hodgkin's Lymphoma Patients
11 December 2005 - 1:15AM
PR Newswire (US)
INDIANAPOLIS, Dec. 10 /PRNewswire-FirstCall/ -- Data presented
today offer evidence that an investigational targeted therapy may
be useful in treating patients with the most common form of
non-Hodgkin's lymphoma (NHL). The five-year survival rate of U.S.
patients with NHL is only 59 percent with standard therapies,
according to the Lymphoma Research Foundation. Diffuse large B-cell
lymphoma (DLBCL) is the most frequent form of NHL (1). Conventional
therapies improve outcomes for some patients, but new treatment
options are always needed. Phase II data presented today at the
American Society of Hematology (ASH) 47th Annual Meeting and
Exposition in Atlanta, Georgia, showed enzastaurin HCl, an
investigational compound from Lilly Oncology, slowed the
progression of DLBCL in several patients pretreated with
chemotherapy. "The use of enzastaurin in relapsed diffuse large
B-cell lymphoma is important for two reasons," said Margaret A.
Shipp, M.D. director of Dana- Farber/Harvard Cancer Center's
lymphoma program and the senior investigator in the clinical trial.
"One, it represents a rational inhibitor of an identified target
and, two, several patients with aggressive chemo-insensitive
disease have had prolonged responses to this single, oral agent."
Enzastaurin inhibits the PKC-Beta and AKT/P13 pathways. This
protein, PKC-Beta, stimulates cell growth. Based on scientific
rationale from initial multicenter studies led by Shipp and from
independent confirmatory studies by other investigators, an
overexpression of PKC-Beta was identified as being linked to poor
outcomes for patients with DLBCL. Enzastaurin, created to target
PKC-Beta, was seen as a worthy candidate for further study in these
patients. In addition, preclinical data indicate that enzastaurin
may have additional effects on cutting off the tumor's blood supply
(anti- angiogenesis), increasing the natural death of tumor cells
(apoptosis) and reducing the cell's ability to reproduce (cell
proliferation). The Phase II multicenter clinical trial evaluated
55 DLBCL patients previously treated with a median of two other
therapies, but like many patients with this aggressive cancer, they
experienced relapses. Data, presented at ASH by Michael J.
Robertson, director of Indiana University Cancer Center's lymphoma
program, showed 22 percent (12 of 55) of study participants treated
with enzastaurin were free of disease progression for two months. A
quarter of those patients remained progression free with continued
responses of 1.5 years to more than three years in duration.
Overall, enzastaurin was well tolerated in this patient population
and clinical results show that patients treated with enzastaurin
experienced minimal side effects. Seven reports of grade 3 side
effects were reported in this trial which included fatigue,
thrombocytopenia (a low level of platelets in the blood), headache,
motor neuropathy (pain, numbness and weak muscles), and edema
(swelling caused by excess fluid), with only one patient
experiencing grade 4 hypomagnesemia (low levels of magnesia in the
blood). "We at Lilly are excited by the potential for enzastaurin
in the treatment of patients with recurrent diffuse large B-cell
lymphoma," said Richard Gaynor, M.D., vice president, cancer
research and global oncology platform leader for Eli Lilly and
Company. "We're also evaluating enzastaurin for patients with
glioblastoma, a form of primary brain cancer with few adequate
treatments. Our commitment to continuous innovation in cancer care
has resulted in enduring therapies such as Gemzar(R) and Alimta(R),
which are already helping patients with pancreatic, bladder,
breast, mesothelioma and lung cancers." Today's data support
continued development of enzastaurin, and Lilly will soon begin
enrolling patients in a Phase III registration trial. Researchers
will be evaluating enzastaurin to determine if it can delay relapse
in patients who have already undergone treatment for DLBCL and have
achieved remission following the standard of care. In addition to
non-Hodgkin's lymphoma and glioblastoma, enzastaurin will be
evaluated in other tumor areas such as colon cancer, non-small cell
lung cancer and mantle cell lymphoma. Non-Hodgkin's Lymphoma
Non-Hodgkin's lymphoma is the most common cancer of the lymphatic
system. Since the early 1970s, U.S. incidence rates for
non-Hodgkin's lymphoma have nearly doubled. Over the 25-year period
between 1973 and 1998, new cases of NHL seen each year escalated
almost 83 percent, among the highest increases of any cancer. Of
the nearly 500,000 Americans with lymphoma, 332,000 have this form.
In 2005, approximately 56,390 new cases of NHL will be diagnosed
and 19,200 Americans will die from the disease (2). About Eli Lilly
and Company Lilly, a leading innovation-driven corporation, is
developing a growing portfolio of first-in-class and best-in-class
pharmaceutical products by applying the latest research from its
own worldwide laboratories and from collaborations with eminent
scientific organizations. Headquartered in Indianapolis, Ind.,
Lilly provides answers -- through medicines and information -- for
some of the world's most urgent medical needs. P-LLY This press
release contains forward-looking statements about the potential of
the investigational compound enzastaurin (LY317615) and reflects
Lilly's current beliefs. However, as with any pharmaceutical
product under development, there are substantial risks and
uncertainties in the process of development and regulatory review.
There is no guarantee that the product will receive regulatory
approvals, or that the regulatory approval will be for the
indication(s) anticipated by the company. There is also no
guarantee that the product will prove to be commercially
successful. For further discussion of these and other risks and
uncertainties, see Lilly's filing with the United States Securities
and Exchange Commission. Lilly undertakes no duty to update
forward-looking statements. (1) Lymphoma Research Foundation,
"Learning About Lymphoma," Lymphoma Research Foundation, February
2005, http://www.lymphoma.org/ (November 9, 2005) (2) Lymphoma
Research Foundation, "Learning About Lymphoma," Lymphoma Research
Foundation, February 2005, http://www.lymphoma.org/ (November 9,
2005) --------------------------------------------------- Gemzar(R)
(gemcitabine, Eli Lilly and Company) Alimta(R) (pemetrexed, Eli
Lilly and Company) (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company CONTACT: Gregory L. Clarke of Eli Lilly and
Company, +1-317-276-5222 (office), Email:
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