Lilly Targeted Agent Shows Promise in Treating Primary Brain Cancer
May 17 2005 - 7:45AM
PR Newswire (US)
Lilly Targeted Agent Shows Promise in Treating Primary Brain Cancer
Investigational Oral, Targeted Agent Shrinks Tumor with Minimal
Side Effects in Glioblastoma INDIANAPOLIS, May 17
/PRNewswire-FirstCall/ -- Preliminary results from a Phase II
clinical trial show patients with recurrent glioblastoma
multiforme, a form of primary brain cancer, experienced a
significant tumor response rate with minimal side effects when
treated with enzastaurin, an oral, targeted agent under development
at Eli Lilly and Company (LLY).(1) Enzastaurin is the first
targeted agent of Lilly Oncology to enter into late stage clinical
development heralding a new phase of innovation for the group,
which has produced Gemzar(R) (gemcitabine HCl) and Alimta(R)
(pemetrexed), two of the world's leading chemotherapy agents.
"Recurring glioblastoma is a desperate disease for which there are
very few adequate treatments," said Howard Fine, M.D., chief of
Neuro-Oncology at the National Cancer Institute and lead author of
the study, which was presented today at the annual meeting of the
American Society of Clinical Oncology (ASCO). Glioblastoma, a type
of brain cancer, is part of the larger group of tumors that impact
the central nervous system, known as gliomas. Patients with highly
recurrent glioblastoma are usually at a more advanced stage of the
disease and correspondingly may face altered brain function or
death due to the tumor's rapid growth rate. Radiation therapy is
the most effective treatment following surgery. Almost all patients
receive some form of radiation therapy. Gliomas -- tumors of the
brain -- are among the most angiogenic of all tumors, meaning the
tumor has the ability to grow by drawing on blood from surrounding
vessels at a very rapid rate. The inhibition of tumor angiogensis
may offer the potential as a highly effective form of therapy. The
Phase II study presented at ASCO included 92 patients with
recurrent glioblastoma who had failed more than one prior regimen
of chemotherapy. Patients' treatment consisted of an oral fixed
dose of 500 mg of enzastaurin, administered daily. Treatment was
allowed to continue indefinitely depending upon the patient's
response to the drug. Results show that tumor shrinkage was evident
in patients who received enzastaurin, with a corresponding response
rate of 20 - 25 percent. Overall, enzastaurin was well tolerated in
this patient population and clinical results show that patients
experienced minimal side effects while administered enzastaurin.
The most common side effect was thrombocytopenia, which is a low
platelet count. "Enzastaurin's mode of action is unique because it
impacts tumor cells in multiple ways, while other targeted agents
act on one pathway," said Richard Gaynor, M.D., vice president of
cancer research and clinical investigation at Lilly. Gaynor said
that in the trial enzastaurin stopped the flow of blood to
patients' tumors, resulting in disruption of tumor growth and -- in
most cases -- tumor shrinkage. In addition to prohibiting
angiogenesis of tumor cells, enzastaurin inhibits the cell pathway
signaling through the PKC-beta and Pl3 kinase/AKT pathways, two of
the pathways that are vital to the survival of tumor cells.(2)
These pathways are frequently activated in glioblastoma and because
cancer cells don't follow the checks and balances seen in normal
cells, the tumors grow unchecked. Furthermore, tumor-induced
angiogenesis requires activation of these pathways. Enzastaurin
causes tumor cells to turn off those survival signals.
Consequently, enzastaurin has both direct tumor cell killing
effects (apoptosis) and indirect, tumor-starving effects
(antiangiogensis) said Gaynor. Gaynor said final results from the
Phase II study are expected by 2006 and Lilly is currently
designing the protocol for the Phase III study of enzastaurin in
recurrent glioblastoma. The Phase III study will further verify the
efficacy and safety of the drug in a larger patient population.
About Glioblastoma Glioblastoma is the most aggressive and
malignant form of glioma, a type of primary brain cancer. Surgery
is often used to treat gliomas, along with radiation. However,
since surgery and radiation fail to cure the disease, doctors may
turn to additional radiation or chemotherapy. In early stages
glioblastoma tumors often grow without symptoms and therefore can
become quite large before symptoms arise. When the tumor becomes
symptomatic, tumor growth is usually very rapid and is accompanied
by altered brain function, and if left untreated the disease
becomes lethal. Although primary treatment is often successful in
temporarily stopping the progression of the tumor, glioblastomas
almost always recur and become lethal. 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. Additional
information about Lilly is available at http://www.lilly.com/ .
P-LLY This press release contains forward-looking statements about
the potential of the investigational compound enzastaurin
(LY-317615) 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. Enzastaurin (LY-317615, Lilly)
Gemzar(R) (gemcitabine HCl), Lilly Alimta(R) (pemetrexed), Lilly
(1) Results from a phase II trial of Enzastaurin HCl (LY317615) in
patients with recurrent high grade gliomas; H. Fine, L. Kim, C.
Royce, D. Draper, I. Haggarty, H. Elinzano, D. Thorton (2) Results
from clinical trial: The PKC-Beta selective inhibitor, Enzastaurin
HCl (LY317615), suppresses GSK3Beat phosphorylation, induces
apoptosis and suppresses growth of human colon cancer and
glioblastoma xenografts; J. Graff, A. McNulty, K. Hanna, B.
Konicek, R. Lynch, S. Bailey (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 (U.S. Media),
+1-317-276-5222, pager: +1-877-892-7864, Email: , or Carla Cox (Non
- U.S. Media), +1-317-651-1473, pager: +1-888-446-5740, Email: ,
both of Eli Lilly and Company
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