HOUSTON, July 1 TX-Agennix-Drug-Study
HOUSTON, July 1 /PRNewswire/ -- Agennix Incorporated today announced the
publication of final results from a Phase 2 monotherapy trial with
talactoferrin alfa in patients who had failed previous treatment for advanced
or metastatic renal cell carcinoma (RCC). Results from the study, which were
reported in the July 1 issue of the journal 'Cancer' (volume 113, number 1),
demonstrate that talactoferrin is active in RCC, has a favorable toxicity
profile, and is a promising candidate for further study in this disease.
The talactoferrin monotherapy single arm trial was conducted at six
leading U.S. centers and enrolled 44 patients who had all failed prior
treatment for advanced or metastatic RCC. The study met the pre-defined
target of demonstrating an improvement in the fourteen week progression-free
survival (PFS) rate relative to published results in this population.
Additional evidence of anti-cancer activity included the occurrence of partial
responses and an apparent increase in median PFS and median overall survival
(OS) relative to published results. As in previous studies with
talactoferrin, the drug was well tolerated.
"The results seen with talactoferrin monotherapy in this Phase 2 trial are
promising," said Dr. Eric Jonasch, Assistant Professor, MD Anderson Cancer
Center, Houston, Texas, and the first author of the study. "The trial results
indicate that additional studies of talactoferrin in patients with RCC are
warranted either as a single agent or in combination with one of the newer
targeted therapies. Previously conducted preclinical studies combining
talactoferrin with sunitinib are supportive for examining this combination in
a randomized trial in patients with advanced or metastatic RCC."
Agennix also announced the receipt of Orphan Medicinal Product designation
from the European Medicines Agency (EMEA) for RCC. The Company had previously
announced receipt of Orphan Drug designation from the U.S. Food and Drug
Administration (FDA) for the same indication.
Final Phase 2 Study Results
The Phase 2 talactoferrin monotherapy trial was an open label, 44-patient,
single arm trial conducted at six leading U.S. sites. To be eligible,
patients with histologically confirmed metastatic or unresectable RCC had to
have disease progression after being treated with at least one prior regimen
of systemic therapy. Computed tomography (CT) scan documentation of disease
progression following the most recent therapy was required. Talactoferrin was
administered at a dose of 1.5 grams twice a day in 14-week cycles (12 weeks
on, two weeks off) for up to four cycles or until disease progression. The
study's co-primary endpoints were to detect an increase in the 14-week
progression-free survival (PFS) rate from 20% to 40% or a 12.5% response rate,
either of which were considered to be clinically significant. In a Phase 2
trial of Avastin in second line RCC patients, the placebo arm had a 4-month
PFS rate of 20%, and was chosen as the historical reference.
All 44 patients were included in the intent-to-treat (ITT) population.
The study met the pre-defined target with a 14-week PFS rate of 59% (p<0.0001
for comparison to 20%). The response rate was 4.5%, with 70.5% of patients
demonstrating stable disease for at least 8 weeks. The disease control
(complete or partial response + stable disease) rate was 75%. The median PFS
was 6.4 months. The median overall survival (OS) was 21.1 months, and the 1
year survival rate was 77%. Talactoferrin was well tolerated with no
significant hematological, renal or hepatic toxicities reported. In addition,
there were no drug related serious adverse events.
About EMEA Orphan Medicinal Product Designation
The Regulation on Orphan Medicinal Products in the European Union (EU)
provides incentives for companies developing and marketing therapies for rare
diseases, defined as those affecting fewer than five in 10,000 people in the
EU. The Regulation grants companies with Orphan Medicinal Product designation
market exclusivity for a particular indication for a period of ten years
following Marketing Authorization Approval by the EMEA. Orphan Medicinal
Product designation also facilitates the drug development process by providing
companies with protocol assistance, clinical trial support, direct access to
the Centralized Procedure, grant funding for research, and waiver or reduction
of application fees.
The Company had previously received Orphan Drug designation for RCC from
the U.S. FDA.
"We are very pleased that the EMEA recognizes that our lead product,
talactoferrin alfa, has potential as a treatment for patients with RCC, and we
are planning additional trials in this indication including a randomized,
placebo-controlled Phase 2b trial of talactoferrin in combination with a
standard first-line therapy," said Rajesh Malik, M.D., Chief Medical Officer
of Agennix.
About the Planned Phase 2b First-Line Combination Therapy RCC Trial
Building on the results of the positive Phase 2 trial with single agent
talactoferrin, preparations are underway to conduct a Phase 2b trial in
200-250 previously untreated patients with advanced or metastatic RCC as part
of a first-line combination therapy regimen. Patients will be randomly
assigned to receive a standard therapy plus either oral talactoferrin or
placebo. The primary endpoint will be assessment of PFS, with additional
endpoints including response rate, OS, and safety.
About Talactoferrin Alfa
Talactoferrin, a novel dendritic cell recruiter and activator (DCRA), is a
unique recombinant form of human lactoferrin, an important immunomodulatory
protein.
In 1988, scientists at Baylor College of Medicine, Houston, Texas,
discovered a way to produce this protein in the laboratory, thus paving the
way for testing its potential to help fight serious diseases that cause
enormous suffering worldwide.
Lactoferrin, found in the highest concentration in milk, is expressed
throughout the body in immune cells and on all body surfaces exposed to the
external environment. Lactoferrin plays an important role in helping to
establish the immune system, including the Gut Associated Lymphoid Tissue
(GALT), in infants. Talactoferrin is produced in Aspergillus niger, a
filamentous fungus, and is structurally identical to native human lactoferrin
in all material respects, differing only in its glycosylation.
Talactoferrin is an orally administered protein that mediates its activity
through the gut and the GALT -- the largest lymphoid organ in the body. It
acts through a novel mechanism of dendritic cell recruitment and activation.
Following oral administration, talactoferrin is transported by the M-cells
into the small intestinal Peyer's Patches, where it recruits circulating
immature dendritic cells bearing tumor antigens to the GALT and induces their
maturation. DC maturation in the presence of tumor antigens and lymphoid
effector cells induces a strong systemic innate and adaptive immune response
mediated by anti-cancer Natural Killer (NK) cells, CD8+ lymphocytes and NK-T
cells. This results in the activation of tumor-draining lymph nodes, cellular
infiltration of distant tumors and tumor-cell death. Mounting the initial
immune response in the GALT -- away from the primary tumor and using a
physiologically important pathway -- minimizes the effect of the cancer's
local immunosuppressive defenses.
About Renal Cell Carcinoma (RCC) RCC is the most common type of kidney
cancer, accounting for approximately 90 percent of kidney tumors. In the
United States, RCC affects over 40,000 patients per year, and is responsible
for close to 13,000 deaths. Kidney cancer is uncommon under age 45, and its
incidence is highest between the ages of 55 and 84.
Once RCC is metastatic, it is difficult to treat, and median survival is
between one and two years. A number of different modalities are available for
the treatment of metastatic RCC, including immunotherapy, chemotherapy,
targeted therapy, and/or radiation therapy. Some of the targeted therapies
include multi-targeted tyrosine kinase inhibitors such as sunitinib (Sutent)
and sorafenib (Nexavar), inhibitors of the mammalian target of rapamycin, such
as temsirolimus (Torisel), and the anti-vascular endothelial growth factor
(VEGF) antibody, bevacizumab (Avastin). Although each agent can provide some
benefit in a subset of patients, complete response is exceedingly rare, and
most patients with metastatic RCC die of their disease. Additional therapy is
clearly needed.
About Agennix
Agennix is a private biotechnology company developing a first-in-class
molecule with activity in several types of cancer and in other indications
with unmet medical needs. This molecule, talactoferrin, is a targeted
dendritic cell recruiter and activator with a novel mechanism of action.
Agennix is preparing to initiate Phase 3 trials in two NSCLC indications
(talactoferrin in combination with chemotherapy in previously untreated
patients and talactoferrin monotherapy in patients who have failed two or more
previous therapies), a Phase 2b trial in renal cell cancer, and Phase 2 trials
in other indications. Talactoferrin's potential advantages in NSCLC and in
other tumor types include its promising anti-tumor activity, its well
tolerated safety profile including a reduction of some chemotherapy
toxicities, its oral route of administration, and its apparent usefulness in
multiple tumor types both as a single agent and in combination with other
drugs. Agennix retains all of the commercial and economic rights to
talactoferrin for all indications worldwide, and has strong global
intellectual property protection for talactoferrin.
More information about Agennix is available on the Company's web site at
http://www.agennix.com.
SOURCE Agennix Incorporated
