Company Also Announces Receipt of Fast Track Designation from FDA, Favorable Scientific Advice from EMEA and Phase 3 Plans for the Non-Small
Cell Lung Cancer Monotherapy Indication
SANTA MONICA, Calif., Feb. 26 /PRNewswire/ -- Dr. Giuseppe Giaccone, Chief of the Medical Oncology Branch at the National Cancer Institute, presented the final results from a positive double-blind, placebo-controlled Phase 2 trial with talactoferrin alfa in non-small cell lung cancer (NSCLC). The data were presented at the 2008 Targeted Therapies for the Treatment of Lung Cancer meeting in Santa Monica, California.
This was the second successful, randomized, double-blind, placebo- controlled trial with oral talactoferrin in NSCLC. The first was with talactoferrin in combination with first-line chemotherapy.
The monotherapy trial, which compared single-agent oral talactoferrin to placebo in patients with NSCLC who had failed previous chemotherapy, met its primary endpoint of improvement in overall survival. Secondary efficacy endpoints also showed improvement consistent with the primary endpoint results. Oral talactoferrin was well tolerated in this patient population with fewer adverse events observed in the talactoferrin arm. Earlier data from this trial were presented at the 2007 American Society of Clinical Oncology (ASCO) Annual Meeting, and at the 2007 World Conference on Lung Cancer Annual Meeting.
"The improvement in overall survival seen with talactoferrin monotherapy in this Phase 2 study is exciting," said Dr. Jeffrey Crawford, Chief of Medical Oncology, Duke University Medical Center, Durham, North Carolina. "Importantly, this effect was observed in a treatment-refractory patient population with few remaining therapeutic options, and talactoferrin was well tolerated with few adverse events."
Agennix also announced the receipt of Fast Track designation from the U.S. Food and Drug Administration (FDA) for the clinical development of talactoferrin as a single agent in patients with NSCLC who have failed two or more previous therapies. In addition, favorable Scientific Advice was received from the European Medicines Agency (EMEA) indicating that the planned single pivotal Phase 3 global trial with talactoferrin monotherapy in patients who have failed two or more previous therapies can also support a Marketing Authorization Application (MAA) in the European Union.
Final Phase 2 Study Results
The Phase 2 trial was a double-blind, placebo-controlled, single-agent study evaluating the safety and activity of oral talactoferrin monotherapy in 100 patients with stage IIIB/IV NSCLC whose cancer had progressed after previous chemotherapy. Patients received standard supportive care and were randomly assigned to receive either oral talactoferrin (1.5 g; n=47) or placebo (n=53) twice a day. Patients did not receive any other anti-cancer therapy while on the trial. Treatment was administered in 14-week cycles (12 weeks on, two weeks off) for up to three cycles or until disease progression. All 100 patients were included in the intent-to-treat (ITT) population. The 81 patients who had at least one CT scan after initiating treatment were prospectively defined as the evaluable population. The primary endpoint was overall survival in the 100-patient ITT population.
The study met its pre-specified primary endpoint - improvement in overall survival. In the 100-patient ITT population, median overall survival was 65% higher in the talactoferrin group compared to the placebo group - 6.1 months versus 3.7 months (hazard ratio=0.68; p=0.0404). In the 81-patient prospectively-defined evaluable population, the median overall survival was 80% higher in the talactoferrin group compared to the placebo group - 7.9 months versus 4.4 months (hazard ratio=0.59; p=0.0171). The six-month survival rate in the ITT population was also significantly better in the talactoferrin group (49%) compared to the placebo group (28%; p=0.0276). Overall survival improvement trends were consistently observed across subsets of patients grouped by major prognostic factors, including disease stage, performance status, and line of therapy. Positive trends were also observed on the secondary endpoints including progression-free survival (PFS) and disease control rate.
In addition to the efficacy improvements, oral talactoferrin was well tolerated in this group of patients with previously treated NSCLC. Adverse events (AEs) were generally mild, and no drug-related serious AEs were reported. There were 26% fewer AEs and 48% fewer Grade 3/4/5 AEs in the talactoferrin group relative to the placebo group (p=0.0037 and p=0.0024, respectively).
"These exciting data hold promise for the historic battle being conducted to find effective treatments for the most lethal forms of cancer," said Dr. Peter Traber, President of Baylor College of Medicine, where talactoferrin was first produced in the laboratory. "It is our sincere hope that the Phase 3 trials of talactoferrin will be successful and this drug can eventually be used globally."
About the Phase 3 NSCLC Monotherapy Study
Building on the results of the two positive Phase 2 studies, preparations are underway for Phase 3 trials with talactoferrin in two NSCLC indications: (i) first-line in combination with chemotherapy, and (ii) monotherapy in patients who have failed two or more previous therapies.
The pivotal Phase 3, multinational, randomized, double-blind, placebo- controlled monotherapy study will enroll 720 patients with Stage IIIB or IV NSCLC who have failed two or more previous therapies. Patients will receive standard supportive care and be randomly assigned (2:1) to receive single- agent treatment with either oral talactoferrin or placebo until disease progression. Overall survival will be the primary endpoint for approval. Secondary endpoints include adverse event reductions, progression-free survival, confirmed response rate, duration of response, disease control rate and safety.
The Phase 3 NSCLC monotherapy trial will be conducted concurrently with the pivotal Phase 3 first-line combination with chemotherapy NSCLC trial. Both studies will be conducted at many of the same sites and in partnership with the same global contract research organization (CRO). The first-line Phase 3 trial is also supported by a positive double-blind, placebo-controlled Phase 2 trial. For the first-line indication, Agennix has been granted a Special Protocol Assessment and Fast Track designation from the FDA, and has received favorable Scientific Advice from the EMEA. Both Phase 3 studies are expected to be active and recruiting in mid-2008.
FDA Fast Track Designation and EMEA Favorable Scientific Advice
Agennix received Fast Track designation from the FDA for the clinical development of talactoferrin as a single-agent in patients with locally advanced or metastatic NSCLC who have failed at least two prior systemic anti- cancer therapies. The Company had previously received Fast Track designation for first-line treatment of NSCLC in combination with chemotherapy.
Fast Track designation is a process designed to facilitate the development and expedite the review of drugs that treat serious diseases and address unmet medical needs. The NSCLC monotherapy Fast Track designation was granted based on positive, randomized, placebo-controlled Phase 2 results with oral talactoferrin, and the planned Phase 3 pivotal trial.
"We are very pleased that the FDA recognizes that our lead product, talactoferrin alfa, also has potential as a single-agent treatment for patients with NSCLC who have failed previous therapies and who currently have very few options," said Dr. Rajesh Malik, Chief Medical Officer of Agennix.
Agennix also received Scientific Advice from the EMEA indicating that the planned single pivotal Phase 3 global trial with talactoferrin monotherapy in patients who have failed two or more previous therapies will support a MAA in the European Union.
About Talactoferrin Alfa
Talactoferrin, a novel dendritic cell activator (DCA), 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 Non-Small Cell Lung Cancer (NSCLC)
In the United States, lung cancer is the second most frequent cancer in both men (next to prostate cancer) and women (next to breast cancer). It remains the major cause of cancer death, killing more people than breast cancer, prostate cancer and colorectal cancer combined, and accounting for almost 30% of all cancer-related deaths.
NSCLC accounts for approximately 80% of all new lung cancer cases, with approximately 150,000 patients in the United States and 300,000 patients in Europe diagnosed each year. Most patients diagnosed with NSCLC have late- stage disease (Stage IIIB or IV), which is not surgically resectable. The current U.S. standard of care for these patients is systemic chemotherapy. Even with the available therapy, the five-year survival rate for these patients is less than 3%.
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 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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