In-Depth Analysis of Phase 3 Data of Oncophage in Kidney Cancer and Provides Regulatory Update
Wednesday June 7, 10:06 am ET
NEW YORK--(BUSINESS WIRE)--June 7, 2006--Antigenics:
A 43-Percent Improvement Shown in Recurrence-Free Survival in Large Group of Earlier-Stage Kidney Cancer Patients Who Received Oncophage
Antigenics Will Continue to Follow Patients for Overall Survival
Conference Call to Be Held at Today at 9:00 A.M. ET
Antigenics, Inc. (NASDAQ: AGEN - News) today announced that it has completed an in-depth analysis of its Phase 3 study of Oncophage® (vitespen) vaccine in kidney cancer. Review of the data at an international expert panel meeting on June 2, 2006, found that in the full analysis set* (FAS, which represents the true adjuvant patient population intended for the trial), there was a clinically significant improvement in recurrence-free survival (RFS) associated with Oncophage in a well defined subgroup of better-prognosis FAS patients.
Source: Antigenics, Inc.
· This schematic shows the AJCC staging and recurrence-free survival in better prognosis patients receiving Oncophage in Antigenics' Phase 3 trial in renal cell carcinoma. (Graphic: Business Wire) (Graphic: Business Wire). View Multimedia Gallery
It is in this large group of 361 patients - or 60 percent of the total FAS population - that the greatest apparent response to Oncophage versus the observation arm was observed (nominal, two-sided P value of 0.018). In addition, the hazard ratio for this group was 0.567, indicating that patients receiving Oncophage had a 43-percent decreased risk of recurrence compared with patients in the observation arm. This better-prognosis subgroup includes patients whose disease was stage I (high-grade), stage II (high-grade), and stage III T1, T2 and T3a (low-grade), as defined by the American Joint Committee on Cancer (AJCC).
"These analyses have identified a clinically relevant adjuvant patient population that appears more responsive to treatment with Oncophage," said Christopher G. Wood, MD, associate professor of urology at M. D. Anderson Cancer Center in Houston, and lead investigator of the trial. "These results certainly warrant further exploration of the use of Oncophage in kidney cancer patients."
"The substantial improvement observed in the better-prognosis patients - who account for a significant proportion of the total enrolled in this trial - further support the clinical and preclinical findings on Oncophage generated to date," said Garo H. Armen, PhD, chairman and CEO of Antigenics. "Clearly, cancer vaccines work differently than other cancer drugs. Their effect is best measured on earlier-stage patients, which is consistent with signs of clinical activity with a number of other vaccines being studied in the clinic."
Study Findings
The Phase 3, randomized, international, multicenter, open-label trial (C-100-12) involved 728 patients whose renal cell carcinoma (the most common type of kidney cancer) was at high risk of recurrence after nephrectomy (surgical removal of the diseased kidney). A subsequent independent review by the trial's Clinical Events Committee (CEC), comprised of three radiologists and one oncologist, found that 124 patients had disease at baseline; consequently, 604 of the 728 randomized patients were eligible for analysis of the study's primary endpoint, recurrence-free survival.
Per protocol, the study population included those with stage I (high-grade), stage II (high-grade), stage III and stage IV (nonmetastatic) disease. Patients were randomized in a 1:1 ratio into two arms: nephrectomy plus Oncophage vaccination (treatment arm), or nephrectomy alone (observation arm). The arms were well balanced for all known prognostic factors.
Primary analysis of study endpoints focused on the FAS population (the 604 patients who did not have radiologically apparent disease postsurgery). Results reported previously in March 2006 had indicated a trend in favor of recurrence-free survival for the Oncophage arm in the overall patient population. The Kaplan-Meier curve (an estimate of the cumulative probability of recurrence-free survival) below shows that following additional analysis of the data, there was a clinically significant improvement in recurrence-free survival for better-prognosis patients in the FAS population (stages I (high-grade), II (high-grade), and III T1, T2 and T3a (low-grade)) in the Oncophage arm compared with the observation arm (nominal, two-sided P value of 0.018).
In addition to the overall and better-prognosis FAS populations, analysis showed a trend in favor of Oncophage for recurrence-free survival in the intent-to-treat (ITT), randomized eligible set (mITT) and evaluable population sets.
Overall survival, the secondary endpoint of the study, was also assessed in the 604 patients included in the FAS population. Preliminary analysis indicates a trend against Oncophage; however, the survival data are immature. The company believes the data are also likely influenced by missing information caused by patients who were lost to follow-up or withdrew consent. At the time of data cut-off in January 2006, 31 patients (10.3 percent) had died in the Oncophage arm versus 22 patients (7.2 percent) in the observation arm. As of May 2006, seven additional deaths have been reported, with only two in the Oncophage arm and five in the observation arm. Antigenics continues to collect and analyze survival data from the trial.
Adverse events reported during the trial were generally mild and expected. The more frequently reported adverse events were mainly constitutional in nature or related to the actual injection, and included, but were not limited to, injection site erythema, injection site induration, injection site pain, injection site edema, headache, fatigue and rash.
Antigenics Announces Results of Discussions With FDA
Antigenics also announced that it met with the US Food and Drug Administration (FDA) on May 23, 2006, to discuss the regulatory pathway for Oncophage in kidney cancer. As a result of these discussions, Antigenics will continue to follow patients for overall survival and undertake all efforts to collect missing information on patients lost to follow-up or who withdrew consent. |
