Replies to post #68730 on Biotech Values

[bladerunner1717]

PGS,

I've listened to the CC and every single analyst congratulated the management team on the good/great results.

Ren Benjamin did raise the question of the 24-month data. Another analyst called the 24-month data "disturbing."

Both the CEO and Dr. Thornton argued that what is needed is survival at one year, and that the hazard ratio is the key statistic here for the FDA. They went on to say that the end of the curve is notoriously unreliable because of the few data points. But they argue that even if the curves come together at 24 months, all that means is that TNFerade does not cure the cancer, but that is not the point of the study. The main point they say is to extend survival at one year, and they have done that with at an outstanding hazard ratio. Dr. Thornton pointed out that Tarceva was approved on the basis of a hazard ratio that is not as good as TNFerade.

Doug Swirsky, CFO, said that they now have sufficient clear data to partner the drug.

Is all this pure spin, or does it have some validity?


Bladerunner

[DewDiligence]

>GNVC – this trial is now officially wasting money.<

Does the SAP include futility analyses at the interim looks? (This might have been a good question for the analysts to ask on the CC :- ) )

[DewDiligence]

At ASCO, GNVC is presenting phase-3 TNFerade data from the first
of two intermediate analyses (after approximately 1/3 of the events
needed for the final analysis). Top-line data from this interim analysis
—including HR=0.75 for overall survival—was disclosed in Nov 2008
(#msg-33665755). The abstract below contains a little more color,
but it does not fully explain the oddity of the results, which was the
subject of a thread on this board (#msg-33702334).

The ASCO presentation occurs on Sun May 31. What data will be
presented? According to statements from the company last fall, the
presentation will include the K-M curves for the first interim analysis
(#msg-33717379). Note: the protocol of this trial was changed with
the FDA’s permission in Jan 2008: #msg-25701243.

http://www.abstract.asco.org/AbstView_65_33046.html

›Multicenter randomized controlled phase III clinical trial using TNFerade with chemoradiation in patients with locally advanced pancreatic cancer: Interim analysis of overall survival

Citation: J Clin Oncol 27:7s, 2009 (suppl; abstr 4605)
Abstract No: 4605
Time: Sunday May 31, 8:00 AM to 12:00 PM

Author(s): K. J. Chang, W. Fisher, D. Kenady, J. Klapman, M. Posner, T. Reid, A. Rosemurgy, R. Shah, E. Zervos, PACT Study Group, D. Laheru; University of California Irvine Medical Center, Orange, CA; Baylor College of Medicine, Houston, TX; University of Kentucky Medical Center, Lexington, KY; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; University of Chicago, Chicago, IL; Moores UCSD Cancer Center , La Jolla, CA; Tampa General Hospital, Tampa, FL; University of Colorado Hospital, Aurora , CO; The Brody School of Medicine at East Carolina University, Greenville, NC; Johns Hopkins, Baltimore, MD

Intro: Local control of LAPC [locally advanced pancreatic cancer] with CRT [chemo-radiation therapy] has historically demonstrated survival benefit vs. RT [radiation therapy] alone. TNF is a nonreplicating adenovirus vector delivering human tumor necrosis factor (TNF-alpha). Results from a phase II study with TNF in LAPC indicated a possible survival advantage. To confirm these findings, a randomized, open-label, controlled Pancreatic Cancer Trial with TNF (PACT) study was developed.

Methods: The TNF arm received a 5 wk treatment of qw intratumoral injection of 4x1011 PU TNF, cont. iv 5-FU and 50.4Gy radiation. The standard of care (SOC) arm received CRT alone. Both groups received adjuvant gemcitabine(G) with the option of erlotinib(E). An IA [interim analysis] of OS (primary efficacy endpoint) was planned after the first third (92) of the expected 276 total death events (from a total patient n=330). Nonparametric logrank of OS was planned; in addition, a lognormal model was used to account for an evident separation of the survival curves after the median.

Results: 185 pts were available for OS analysis (117-TNF+SOC and 68-SOC). Survival in the TNF+SOC group demonstrated a HR of 0.753 (CI [0.494 - 1.15]) relative to SOC. Best fit parametric lognormal analysis indicated a median survival of 11.1 mo with TNF+SOC and 8.7 mo with SOC; nonparametric methods indicated a MS of 9.9 mo for both arms, with a pronounced "late effect" (75th percentile 19.4 mo with TNF+SOC and 11.8 mo with SOC). Prognostic information (G and E use, stage, etc) indicated equivalent distribution between groups.

Conclusions: HR results of the OS IA indicate an encouraging trend in favor of the TNF treated group. Parametric medians may better reflect the true HR than nonparametric methods since the latter do not reflect the shape of the OS distribution. A second IA is planned after 2/3 total events.‹