I believe I've also seen MZ comment on INGN, perhaps in the Indications -- Cancer thread. Here's the ASCO abstract:
>>Publication Year: 2001
Visited: 39
1045
A Phase I and Pharmacokinetic Study of Intravenous (IV) p53 Gene Therapy with RPR/INGN-201 in Patients (pts) with Advanced Cancer.
Desiree Hao, Eric K Rowinsky, Leslie A Smetzer, Leonel Ochoa, Lisa A Hammond, Alison Garner, Lon Smith, Karen Parker, J A Merritt, Anthony W Tolcher, Institute for Drug Development, San Antonio, TX; Insitute for Drug Development, San Antonio, TX; Introgen Therapeutics, Houston, TX.
BACKGROUND: Mutation of the tumor suppressor gene, p53 occurs in approximately 50% of all cancers, confers resistance to apoptosis and is associated with a poor prognosis in many malignancies. RPR/INGN-201 is a replication defective, adenoviral vector encoding a wild-type (wt) p53 gene driven by the cytomegalovirus promotor (Ad5CMV-p53). In vitro, various cell lines have been successfully transduced with Ad5CMV-p53. In vivo, expression and function of the transgenic product correlated with tumor regression and improved survival. In early clinical trials, intra-tumoral administration of RPR/INGN-201 has been shown to be safe, with preliminary evidence of activity in lung and head and neck cancers. This study was conducted to evaluate the safety, tolerability and pharmacokinetic profile of RPR/INGN-201 administered IV daily for three days, every 28 days. RESULTS: To date, 10 pts (median age=56, median ECOG performance status=1, male:female=2:3) have received 25 monthly courses of RPR/INGN-201 at escalating doses of 3 x 1010 , 1 x 1011, 3 x 1011 and 1 x 1012 viral particles (vp) per infusion. One pt had grade 2 neutropenia. One of 5 pts treated at 1 x 1012 vp experienced dose limiting, grade 3 diarrhea. Non-hematologic toxicity across all courses has been mild ([less than or equal to] Grade 2) including fever (7 episodes), fatigue (4), arthralgias/myalgias (4), nausea/vomiting (4/3), and diarrhea (3). Four pts have had transient, asymptomatic transaminase elevations ([less than or equal to] grade 2) typically occurring between day 1-2 and resolving by day 4. One pt with metastatic colon cancer was safely treated with 10 cycles of RPR/INGN-201. CONCLUSIONS: IV administration of RPR/INGN-201 represents a novel delivery method for gene therapy with the potential for more widespread delivery of p53 in pts with disseminated cancers. Evaluation of p53 expression in pre- and post-treatment tumor biopsies is pending. IV administration of doses up to 1 x 1012 vp appears well tolerated and accrual at this dose level is ongoing to further define the maximum tolerated dose.<<
Where have I seen Tolcher's name before? Anyhow, here's the accopnying PR:
>>Introgen Adenovirus Demonstrates Safety in Hundreds of Patients; Biosafety Data Presented in 190 Patients at Annual ASCO Meeting
SAN FRANCISCO, May 14, 2001 /PRNewswire via COMTEX/ -- Introgen Therapeutics, Inc. (Nasdaq: INGN chart, msgs) today reported definitive biosafety information on INGN 201, its adenoviral-p53 gene therapy product candidate currently in Phase III clinical testing. These data were presented at the 37th Annual Meeting of the American Society of Clinical Oncology in San Francisco, CA.
The presentation described data from 190 patients treated intra-tumorally and demonstrated that there are no infectious risks associated with the adenoviral vector to the patients treated, or their families. The study further suggests that the adenovirus vector used in the treatment is genetically stable, meaning that there is no recombination or mutation after the administration of the treatment.
"Introgen has amassed the world's largest safety database on adenoviruses with over 500 patients treated with INGN 201, currently in pivotal Phase III trials," said James A. Merritt, M.D., vice president of clinical affairs for Introgen. "No other gene vector system has been tested to the extent that Introgen's adenovirus has in the clinic. Human safety has been evaluated following 8 routes of administration, including injections into various organs and tissues, as an instillation into the bronchial tree, mucosal infiltration into healthy surgical wound margins, and a repeated direct intravenous infusion. In each of these studies, the Introgen adenovirus demonstrates an impressive lack of toxicity, locally and systemically, at therapeutically active doses. By contrast, far less is known about the safety of other viral vectors such as the adeno-associated vectors, due to their less advanced development status. Although the Introgen adenoviral vector is replication- impaired, we believed it important to further demonstrate that the viral vector is not transmitted to members of a close household, under real world conditions. For other virus-based gene therapeutics, especially the replicating systems, this could still represent a concern."
Earlier this year Introgen was awarded U.S. Patent No. 6,194,191 for the commercial scale production of adenovirus. This patent covers the commercial scale production of adenovirus regardless of whether the adenovirus is used as a delivery system for therapeutic genes such as p53, or used directly as a therapeutic agent. Over the past five years adenovirus has become by far the most commonly used vector for direct administration to patients.
The gene therapy field has matured so that, in addition to INGN 201, there are a number of adenoviral products in Phase III, Phase I/II, or randomized Phase II clinical testing. Introgen has established itself as the de facto leader in the manufacture of adenoviral vectors for human trials, and has produced numerous lots of adenoviral product using its patented method.<<
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Anybody have an opinion on INGN's research premium?
Cheers, Tuck |
