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Press Release Source: GenVec, Inc.
Gene Therapy in Combination With Radiation Shows Notable Dose-Related Tumor Shrinkage in Phase Ib Human Trials
Friday November 8, 6:32 pm ET
73% of Patients Experienced Tumor Shrinkage of 25% - 100% Without Any Drug-Related Serious Adverse Events
GAITHERSBURG, Md., Nov. 8 /PRNewswire-FirstCall/ -- GenVec, Inc. (Nasdaq: GNVC - News), a biopharmaceutical company developing locally delivered gene- based medicines, today announced the final results from its Phase Ib clinical trial for its lead oncology product candidate, TNFerade(TM). The results were released in a presentation at the American Society of Clinical Oncology (ASCO) Molecular Therapeutics Symposium being held in San Diego, California.
The Phase Ib clinical trials of TNFerade, principally designed to assess the safety of the product candidate, were conducted at four centers around the country and involved patients with a wide variety of cancers including cancer of the pancreas, breast, lung, head and neck, skin, colon, and rectum. TNFerade showed substantial activity against a broad range of tumor types.
Clinical Observations (30 Patients Evaluable for Activity)
* Twenty-two out of thirty (22/30) patients (73%) showed objective
tumor shrinkage which means that their tumors shrank between 25% and
100% with TNFerade therapy. The objective tumor responses are
classified as Complete Response (CR) 5/30 patients, Partial Response
(PR) 9/30 patients and Minor Response (MR) 8/30 patients in this
study.
* Four out of thirty (4/30) showed stable disease (SD).
* Four out of thirty (4/30) showed progressive disease in the
injected lesion.
* The responses were durable during the follow-up period from 2 to
12 months
* Lower doses of TNFerade (4x10(to the 7th) and 4x10(to the 8th) p.u.)
appeared less effective than the higher dose range
(4x10(to the 9th) - 4x10(to the 11th) p.u.).
- 38% of patients at the lower doses showed progressive disease,
as compared to only 5% of patients at the higher doses
- 55% of patients showed partial or complete responses (PR/CR) at
the high doses as compared to 25% at the lower doses
- There were no CRs at the lower doses, but 23% of the patients
at higher doses showed complete responses.
* Tumor responses were independent of histology or tumor site.
* Three out of four (3/4) patients with pancreatic cancer at the
higher dose levels showed tumor shrinkage (2 PRs, 1 MR). One
patient who has been followed for 18 months showed no disease
progression.
* Some patients had control lesions, which received the same radiation
dose, but did not receive TNFerade. A differential effect was found
in tumors receiving higher TNFerade doses plus radiation versus
tumors receiving radiation only, supporting that the tumor response
in these patients was due to the combination of TNFerade plus
radiation, rather than radiation alone.
Safety Findings (33 Patients Evaluable for Safety)
* TNFerade was well tolerated
* No dose-limiting toxicities (DLT) seen
* No drug-related Serious Adverse Events (SAE) seen
* Serum-TNF levels were not significantly elevated
* No adenovirus detected in blood or urine of patients
* Side effects were all classified as mild.
TNFerade delivers the human tumor necrosis factor alpha (TNF-alpha) gene directly to tumors, using GenVec's proprietary adenovector gene delivery technology. Once inside the tumor, standard radiation therapy triggers a "switch" known as the EGR-1 promoter increasing the localized production of the therapeutic anticancer protein, TNF-alpha.
"We are encouraged by the safety profile of TNFerade, indicating that GenVec's approach of local delivery of TNFerade allows us to potentially harness the well-known anticancer activity of TNF-alpha without the systemic toxicity, which in the past has limited its use," stated Henrik Rasmussen, M.D., Ph.D., Senior Vice President of Clinical Research & Regulatory Affairs for GenVec, Inc. Dr. Rasmussen continued, "Objective tumor shrinkage in 73% of the patients treated in a Phase I study in solid tumors is encouraging. TNFerade appears to have broad-spectrum activity across a large number of tumor types, including tumor types which do not typically respond well to radiation therapy, such as sarcoma, pancreatic cancer and large melanomas."
Dr. Rasmussen explained, "The dose response observed, the differential effect between TNFerade plus radiation as compared to radiation alone in patients with control tumors, and the effect in tumor types not normally sensitive to radiation suggests that the effect seen is more than what would be expected by radiation alone. We have recently begun a randomized controlled Phase IIb study in patients with locally advanced pancreatic cancer and have plans to begin a second Phase II trial in patients with non- metastatic esophageal cancer to further evaluate this promising approach. Additionally, because TNFerade administration does not appear to add significant toxicity, it is well-suited as a potential combination therapy with other front line treatment modalities."
David Robinson, GenVec's Vice President of Marketing & Sales commented, "The market for TNFerade is significant. Each year, in the United States alone, over 500,000 people with solid tumors receive radiation therapy as part of their treatment regimen. Approximately 40% of those are treated for palliation, or ease of symptoms, while 60% receive radiation therapy for curative purposes. GenVec has several goals with TNFerade:
* Improve the therapeutic benefit of standard radiation therapy.
* Identify opportunities for radiation therapy where it is not
generally used.
* Provide a safe, therapeutic option for patients with locally
advanced cancers and solid tumors.
The Phase Ib data on TNFerade met each of these goals and supports our decision to advance as quickly as possible into broader Phase II studies."
The Phase Ib clinical trials for TNFerade in solid tumors were conducted at the Albert Einstein College of Medicine, Montefiore Medical Center in New York; the University of Kentucky Medical Center, Lexington; US Oncology in Dallas, Texas, and University of South Florida Medical Center, Tampa and include patients who have failed standard treatment and who are scheduled to receive radiation therapy for local tumor control. TNFerade is injected directly into the tumors one or two times per week for up to 6 weeks, while patients are receiving their standard radiation therapy. Seven dose levels were tested with 3-6 patients at each dose level.
Cancer is the second leading cause of death in the United States. Approximately 1.2 million new cases are diagnosed in the United States each year, responsible for more than 500,000 deaths per year.
GenVec is a publicly-held biotechnology company focused on the development and commercialization of gene-based therapies that produce medically beneficial proteins at the site of disease. The Company combines its patented gene transfer technologies with proprietary therapeutic genes to create product candidates, such as BIOBYPASS® for cardiovascular disease, TNFerade(TM) for solid tumors and AdPEDF for macular degeneration and diabetic macular edema. Additional information on GenVec is available at its web site located at genvec.com, and in the Company's various filings with the Securities and Exchange Commission. |
