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.
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[Via Healthcare]
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