Washington Editor

Shares in Antigenics Inc. jumped Monday on positive Phase III results of Oncophage (vitespen) in a certain subset of metastatic melanoma patients, data the company expects to shape an eventual trial for approval.

Preliminary findings from the open-label, randomized study, which was not intended for registration, showed that median survival improved by more than 61 percent in the Oncophage-treated arm of all patients characterized as having Stage IV M1a status compared to those who received a physician's choice of treatment regimen. Specifically, survival was extended to 20.9 months as opposed to 12.8 months.

"While these results are not statistically significant, we believe that the improved survival benefit observed with Oncophage signals a meaningful clinical benefit to patients with a large unmet need," Renu Gupta, Antigenics' senior vice president of development, said in a conference call. "This is indeed the first cancer vaccine trial to show an improved survival in this patient population."

As a result, she added, representatives of the New York company expect to discuss the data with the FDA "in the very near future" to develop a registration plan in the patient subset. Sunny Uberoi, Antigenics' vice president of corporate communications, said the study's design remains under development and could begin in the next several months.

"These are very sick patients, as all at Stage IV eventually die," he told BioWorld Today. "Nothing has been proven to be successful at all, so this is the first demonstration in the M1a setting."

Those patients, who were prospectively stratified for the trial, are routinely identified in a clinical setting with distant metastases in the skin, subcutaneous tissue or distant lymph nodes. Gupta noted that M1a patients represent "essentially a better prognostic group" compared to M1b and M1c patients, who have more severe metastases and shorter life expectancies after diagnosis.

In the 322-patient trial, labeled C-100-21, the latter patient subsets proved more difficult to treat. Without releasing specific findings, Gupta said Oncophage-treated M1b patients exhibited a survival benefit akin to physicians' treatments, while Oncophage-treated M1c patients didn't survive as long as the comparator group. Physicians' choices included what Uberoi termed a "highly aggressive" array of therapies such as interleukin-2, dacarbazine/temozolomide-based treatment, complete tumor resection, any other licensed cancer therapies or a combination of them.

He speculated that M1a patients responded better to Oncophage than M1b and M1c patients because it takes "several months for the immune system to ramp up" following the drug's administration, time not available to the more severely diagnosed melanoma patients. Overall, those in the intent-to-treat Oncophage arm (M1a, M1b and M1c patients combined) fared similarly to those in the physician's choice arm in terms of survival - the study's primary endpoint.

"Oncophage has thus far shown what appears to be a pronounced benefit in patients with a better prognostic outcome," Gupta said, "and it is consistent with our expectations of relatively better results with vaccine monotherapy in patients with earlier-stage disease."

Garo Armen, Antigenics' chairman and CEO, said the company originally had minimal expectations from the trial, but he noted that the data "provide a very encouraging signal of activity." He estimated that the patients could represent a $200 million annual market in the U.S.

The FDA has given Oncophage fast-track and orphan drug designations in both metastatic melanoma and renal-cell carcinoma. Findings from a Phase III kidney cancer trial are expected early next year. Oncophage, a patient-specific cancer vaccine that is derived from each individual's tumor, also has been tested in lung, pancreatic and colon cancers.

In addition, Antigenics' portfolio also includes AG-858 (HSPPC-70), a patient-specific cancer vaccine in Phase II for blood cancers. Also, two liposomal cancer treatments, Aroplatin and ATRA-IV, have been studied in a number of clinical trials. Lastly, AG-702/AG-707 is in a Phase I program for genital herpes.

A final analysis of the study C-100-21 data is expected next quarter, and the company continues to work with investigators to present further details at scientific meetings and by way of publications in a peer-reviewed journal.

On Tuesday, its shares (NASDAQ:AGEN) fell 25 cents to $5.43, a retreat from Monday's 13.4 percent gain to $5.68.